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Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men
Park JY, Seok JH, Cho KS, Kang DH, Kim JS, Do SH, Na HS, Jang SA and Ahn RS
The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic-pituitary-adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men.
Parietal-Frontal Pathway Controls Relapse of Fear Memory in a Novel Context
Joo B, Xu S, Park H, Kim K, Rah JC and Koo JW
Fear responses significantly affect daily life and shape our approach to uncertainty. However, the potential resurgence of fear in unfamiliar situations poses a significant challenge to exposure-based therapies for maladaptive fear responses. Nonetheless, how novel contextual stimuli are associated with the relapse of extinguished fear remains unknown.
Differential tractography and whole brain connectometry in primary motor area gliomas resection: A feasibility study
Figueredo LF, Mejía-Cordovez JA, Gomez-Amarillo DA, Hakim F, Pimienta-Redondo HD, Almeida JP, Kehayov I, Angelova P, Apostolov G, Luzzi S, Baldoncini M, Johnson JM and Ordóñez-Rubiano EG
Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT).
Effects of repetitive transcranial magnetic stimulation on fear of cancer recurrence and its underlying neuromechanism
Xu W, Zhao N, Li W, Qiu L, Luo X, Lin Y, Wang W, Garg S, Sun H and Yang Y
Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism.
A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry
Schwantes-An TH, Whitfield JB, Aithal GP, Atkinson SR, Bataller R, Botwin G, Chalasani NP, Cordell HJ, Daly AK, Darlay R, Day CP, Eyer F, Foroud T, Gawrieh S, Gleeson D, Goldman D, Haber PS, Jacquet JM, Lammert CS, Liang T, Liangpunsakul S, Masson S, Mathurin P, Moirand R, McQuillin A, Moreno C, Morgan MY, Mueller S, Müllhaupt B, Nagy LE, Nahon P, Nalpas B, Naveau S, Perney P, Pirmohamed M, Seitz HK, Soyka M, Stickel F, Thompson A, Thursz MR, Trépo E, Morgan TR, Seth D and
Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.
Changes in online marketing and sales practices among non-medical cannabis retailers in 5 US cities, 2022 to 2023
Cui Y, Duan Z, LoParco CR, Vinson K, Romm KF, Wang Y, Cavazos-Rehg PA, Kasson E, Yang YT and Berg CJ
Given the evolving cannabis marketplace (e.g., products, marketing strategies), this study examined online cannabis marketing practices over time.
Understanding the association between fatigue and neurocognitive functioning in patients with glioma: A cross-sectional multinational study
Röttgering JG, Taylor JW, Brie M, Luks T, Hervey-Jumper SL, Phan S, Bracci PM, Smith E, De Witt Hamer PC, Douw L, Weyer-Jamora C and Klein M
Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data.
Hematopoietic Stem-Cell Transplantation: Exploring the Latest Advances and Gaps in Disparities, Psychosocial and Symptom Management Interventions, and Chronic Graft-Versus-Host Disease Care
Trunk AD, Guo M, Budvytyte L, Islam NS, Khera N, Hamilton BK and Amonoo HL
Although allogeneic hematopoietic cell transplantation (HCT) offers a potential for cure for many patients with advanced hematologic malignancies and bone marrow failure or immunodeficiency syndromes, it is an intensive treatment and accompanied by short- and long-term physical and psychological symptoms requiring specialized care. With substantial advances in therapeutic approaches for HCT and supportive care, HCT survivors experience less morbidity and mortality. However, disparities in both HCT access and outcomes persist, and HCT survivors and their caregivers often lack access to much-needed psychosocial care. Additionally, more medical and psychosocial resources are needed to holistically care for HCT survivors with chronic graft-versus-host disease (GVHD). Hence, this chapter focuses on three areas pertaining to advances and gaps in HCT care: disparities in access to and outcomes of HCT, psychosocial and physical symptom management with supportive care interventions, and GVHD prevention and management.
Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly
Niimi Y, Janelidze S, Sato K, Tomita N, Tsukamoto T, Kato T, Yoshiyama K, Kowa H, Iwata A, Ihara R, Suzuki K, Kasuga K, Ikeuchi T, Ishii K, Ito K, Nakamura A, Senda M, Day TA, Burnham SC, Iaccarino L, Pontecorvo MJ, Hansson O and Iwatsubo T
Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.
Integrating family caregivers in older adults' hospital stays: a needed cultural shift
Muntefering C, Kastrinos A, McAndrew NS, Ahrens M, Applebaum AJ, Bangerter L and Fields B
This study aimed to examine perceived barriers and facilitators to caregiver inclusion in the hospital care of older adult family members or friends through the perspectives of (1) hospitalized older adults, (2) caregivers of a hospitalized older adult, (3) healthcare clinicians, and (4) policymakers.
Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial
Stone PC, Minton O, Richardson A, Buckle P, Enayat ZE, Marston L and Freemantle N
To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.
Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA)
Estrella ML, Tarraf W, Kuwayama S, Gallo LC, Salazar CR, Stickel AM, Mattei J, Vásquez PM, Eldeirawi KM, Perreira KM, Penedo FJ, Isasi CR, Cai J, Zeng D, González HM, Daviglus ML and Lamar M
Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited.
Diagnostic staging and stratification in psychiatry and oncology: clarifying their conceptual, epistemological and ethical implications
Tinland J, Gauld C, Sujobert P and Giroux É
Staging and stratification are two diagnostic approaches that have introduced a more dynamic outlook on the development of diseases, thus participating in blurring the line between the normal and the pathological. First, diagnostic staging, aiming to capture how diseases evolve in time and/or space through identifiable and gradually more severe stages, may be said to lean on an underlying assumption of "temporal determinism". Stratification, on the other hand, allows for the identification of various prognostic or predictive subgroups based on specific markers, relying on a more "mechanistic" or "statistical" form of determinism. There are two medical fields in which these developments have played a significant role and have given rise to sometimes profound nosological transformations: oncology and psychiatry. Drawing on examples from these two fields, this paper aims to provide much needed conceptual clarifications on both staging and stratification in order to outline how several epistemological and ethical issues may, in turn, arise. We argue that diagnostic staging ought to be detached from the assumption of temporal determinism, though it should still play an essential role in adapting interventions to stage. In doing so, it would help counterbalance stratification's own epistemological and ethical shortcomings. In this sense, the reflections and propositions developed in psychiatry can offer invaluable insights regarding how adopting a more transdiagnostic and cross-cutting perspective on temporality and disease dynamics may help combine both staging and stratification in clinical practice.
Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.
The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses
Walker RM, Chong M, Perrot N, Pigeyre M, Gadd DA, Stolicyn A, Shi L, Campbell A, Shen X, Whalley HC, Nevado-Holgado A, McIntosh AM, Heitmeier S, Rangarajan S, O'Donnell M, Smith EE, Yusuf S, Whiteley WN and Paré G
Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins' plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.
Study of a PST-trained voice-enabled artificial intelligence counselor for adults with emotional distress (SPEAC-2): Design and methods
Ronneberg CR, Lv N, Ajilore OA, Kannampallil T, Smyth J, Kumar V, Barve A, Garcia C, Dosala S, Wittels N, Xiao L, Aborisade G, Zhang A, Tang Z, Johnson J and Ma J
Novel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms.
Toward a more patient-centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS)
Efficace F, Buckstein R, Abel GA, Giesinger JM, Fenaux P, Bewersdorf JP, Brunner AM, Bejar R, Borate U, DeZern AE, Greenberg P, Roboz GJ, Savona MR, Sparano F, Boultwood J, Komrokji R, Sallman DA, Xie Z, Sanz G, Carraway HE, Taylor J, Nimer SD, Della Porta MG, Santini V, Stahl M, Platzbecker U, Sekeres MA and Zeidan AM
Notable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging availability of oral MDS therapies holds the promise of improving patients' health-related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient-reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease. We provide practical considerations to support investigators in generating high-quality PRO data in future MDS trials. We first describe several challenges that are to be thoughtfully considered when designing an MDS-focused clinical trial with a PRO endpoint. We then discuss aspects related to the design of the study, including PRO assessment strategies. We also discuss statistical approaches illustrating the potential value of time-to-event analyses and their implications within the estimand framework. Finally, based on a literature review of MDS randomized controlled trials with a PRO endpoint, we note the PRO items that deserve special attention when reporting future MDS trial results. We hope these practical considerations will facilitate the generation of rigorous PRO data that can robustly inform MDS patient care and support treatment decision-making for this patient population.
Physical activity among cancer survivors: do neighborhood walkability and metropolitan size play a role?
Narcisse MR, Wang ML, Schootman M, DelNero P, Schwarz AG and McElfish PA
To examine associations between walkability, metropolitan size, and physical activity (PA) among cancer survivors and explore if the association between walkability and PA would vary across United States metropolitan sizes.
Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study
Kim KH, Chung YH, Min JH, Han HJ, Kim SW, Shin HY, Kwon YN, Kim SM, Lim YM, Kim H, Lee EJ, Jeong SH, Hyun JW, Kim SH and Kim HJ
The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD.
Tai Chi compared with cognitive behavioral therapy and the reversal of systemic, cellular and genomic markers of inflammation in breast cancer survivors with Insomnia: A randomized clinical trial
Irwin MR, Hoang D, Olmstead R, Sadeghi N, Breen EC, Bower JE and Cole S
Insomnia contributes to inflammation in breast cancer survivors. This study evaluates whether insomnia treatment reverses inflammation in breast cancer survivors with insomnia.
Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging
Peng KY, Liemisa B, Pasato J, D'Acunzo P, Pawlik M, Heguy A, Penikalapati SC, Labuza A, Pidikiti H, Alldred MJ, Ginsberg SD, Levy E and Mathews PM
The polymorphic APOE gene is the greatest genetic determinant of sporadic Alzheimer's disease risk: the APOE4 allele increases risk, while the APOE2 allele is neuroprotective compared with the risk-neutral APOE3 allele. The neuronal endosomal system is inherently vulnerable during aging, and APOE4 exacerbates this vulnerability by driving an enlargement of early endosomes and reducing exosome release in the brain of humans and mice. We hypothesized that the protective effects of APOE2 are, in part, mediated through the endosomal pathway. Messenger RNA analyses showed that APOE2 leads to an enrichment of endosomal pathways in the brain when compared with both APOE3 and APOE4. Moreover, we show age-dependent alterations in the recruitment of key endosomal regulatory proteins to vesicle compartments when comparing APOE2 to APOE3. In contrast to the early endosome enlargement previously shown in Alzheimer's disease and APOE4 models, we detected similar morphology and abundance of early endosomes and retromer-associated vesicles within cortical neurons of aged APOE2 targeted-replacement mice compared with APOE3. Additionally, we observed increased brain extracellular levels of endosome-derived exosomes in APOE2 compared with APOE3 mice during aging, consistent with enhanced endosomal cargo clearance by exosomes to the extracellular space. Our findings thus demonstrate that APOE2 enhances an endosomal clearance pathway, which has been shown to be impaired by APOE4 and which may be protective due to APOE2 expression during brain aging.
Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
Bradfeld JP, Kember RL, Ulrich A, Balkhiyarova Z, Alyass A, Aris IM, Bell JA, Broadaway KA, Chen Z, Chai JF, Davies NM, Fernandez-Orth D, Bustamante M, Fore R, Ganguli A, Heiskala A, Hottenga JJ, Íñiguez C, Kobes S, Leinonen J, Lowry E, Lyytikainen LP, Mahajan A, Pitkänen N, Schnurr TM, Have CT, Strachan DP, Thiering E, Vogelezang S, Wade KH, Wang CA, Wong A, Holm LA, Chesi A, Choong C, Cruz M, Elliott P, Franks S, Frithiof-Bøjsøe C, Gauderman WJ, Glessner JT, Gilsanz V, Griesman K, Hanson RL, Kaakinen M, Kalkwarf H, Kelly A, Kindler J, Kähönen M, Lanca C, Lappe J, Lee NR, McCormack S, Mentch FD, Mitchell JA, Mononen N, Niinikoski H, Oken E, Pahkala K, Sim X, Teo YY, Baier LJ, van Beijsterveldt T, Adair LS, Boomsma DI, de Geus E, Guxens M, Eriksson JG, Felix JF, Gilliland FD, , Hansen T, Hardy R, Hivert MF, Holm JC, Jaddoe VWV, Järvelin MR, Lehtimäki T, Mackey DA, Meyre D, Mohlke KL, Mykkänen J, Oberfeld S, Pennell CE, Perry JRB, Raitakari O, Rivadeneira F, Saw SM, Sebert S, Shepherd JA, Standl M, Sørensen TIA, Timpson NJ, Torrent M, Willemsen G, Hypponen E, Power C, , McCarthy MI, Freathy RM, Widén E, Hakonarson H, Prokopenko I, Voight BF, Zemel BS, Grant SFA and Cousminer DL
Author Correction: Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons
Hergenreder E, Minotti AP, Zorina Y, Oberst P, Zhao Z, Munguba H, Calder EL, Baggiolini A, Walsh RM, Liston C, Levitz J, Garippa R, Chen S, Ciceri G and Studer L
eHealth mindfulness-based music therapy for patients undergoing allogeneic hematopoietic stem cell transplantation: A pilot randomized controlled trial protocol
Fleszar-Pavlovic SE, Esquives BN, Brito AE, Sia AM, Kauffman MA, Lopes M, Moreno PI, Koru-Sengul T, Gong R, Wang T, Wieder ED, Rueda-Lara M, Antoni M, Komanduri K, Lesiuk T and Penedo FJ
Allogeneic stem cell transplantation (allo-SCT) is the preferred therapy for patients with high-risk or relapsed hematologic malignancies, but may be complicated by psychological distress (e.g., depression, anxiety) and symptom burden (e.g., fatigue, pain). Mindfulness-based music therapy (MBMT), a relatively novel integrative medicine intervention that draws from mindfulness and music therapy principles, has shown promise in improving psychosocial outcomes and symptom burden in cancer patients. We outline an eHealth-based MBMT (eMBMT) intervention protocol examining: (1) feasibility, acceptability, and intended effects of eMBMT in improving HRQOL, symptom burden, and clinical markers of disease activity (e.g., infections), and (2) the extent to which eMBMT music therapy component-associated improvements in HRQOL, symptom burden, and disease activity are mediated by improvements in psychosocial and physiological (e.g., systemic inflammation, immune recovery) adaptation.
Meta-analysis of shotgun sequencing of gut microbiota in Parkinson's disease
Nishiwaki H, Ueyama J, Ito M, Hamaguchi T, Takimoto K, Maeda T, Kashihara K, Tsuboi Y, Mori H, Kurokawa K, Katsuno M, Hirayama M and Ohno K
We aimed to identify gut microbial features in Parkinson's disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that species Akkermansia muciniphila was increased in PD, while species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also cause neuroinflammation in PD.
Correlates of intention to screen for cervical cancer among adult women in Kyotera District, Central Uganda: a community based cross-sectional study
Kabanda R, Kiconco A, Ronald A, Beyer KMM and John SA
Cervical cancer continues to pose a major public health challenge in low-income countries. Cervical cancer screening programs enable early detection and effectively reduce the incidence of cervical cancer as well as late-stage diagnosis and mortality. However, screening uptake remains suboptimal in Uganda. This study assessed correlates of intention to screen for cervical cancer among women in the Kyotera district of Central Uganda.
Validation and responsiveness of the English version of the Chemotherapy-Induced Alopecia Distress Scale (CADS) in breast cancer patients
Kraehenbuehl L, Kang D, Bang AS, Ketosugbo KF, Hay J, Patil S, Goldfarb S, Cho J and Lacouture ME
This study aimed to validate the Chemotherapy-Induced Alopecia Distress Scale (CADS) in a diverse English-speaking population and patients with endocrine treatment-induced alopecia (EIA).
Development and Validation of a Survey to Assess Sexual Health in Female Partners of Patients with Prostate Cancer
Loeb S, Gupta N, Wittmann D, Nelson CJ, Mulhall JP, Salter CA, Byrne N, Sanchez Nolasco T, Zebib L, Garrett L and Schofield E
Prostate cancer (PCa) diagnosis and treatment can have a significant negative impact on sexual health, affecting patients and their partners; however, the impact on partners is insufficiently addressed in current practice.
Interventions for smoking cessation in hospitalised patients
Streck JM, Rigotti NA, Livingstone-Banks J, Tindle HA, Clair C, Munafò MR, Sterling-Maisel C and Hartmann-Boyce J
In 2020, 32.6% of the world's population used tobacco. Smoking contributes to many illnesses that require hospitalisation. A hospital admission may prompt a quit attempt. Initiating smoking cessation treatment, such as pharmacotherapy and/or counselling, in hospitals may be an effective preventive health strategy. Pharmacotherapies work to reduce withdrawal/craving and counselling provides behavioural skills for quitting smoking. This review updates the evidence on interventions for smoking cessation in hospitalised patients, to understand the most effective smoking cessation treatment methods for hospitalised smokers.
Interest in I-PrEP and Willingness to Participate in Clinical Trials Among Men and Transfeminine Persons Who have Sex with Men in Sub-Saharan Africa: Quantitative and Qualitative Findings from HPTN 075
Sandfort TGM, Kreniske P, Mbeda C, Reynolds D, Tshabalala G, Madiwati B, Ogendo A, Dominquez K, Panchia R, Gondwe D, Hamilton EL, Guo X and Cummings V
This study explored interest in injectable PrEP (I-PrEP) and willingness to participate in clinical trials testing new biomedical HIV prevention strategies among men and transfeminine persons who have sex with men (MSM & TGP), using data collected in the HIV Prevention Trials Network (HPTN) 075 study, which took place at sites in Kenya, Malawi, and South Africa. Data result from a survey among 267 18-44 years old HIV negative participants, complemented with semi-structured interviews with 80 purposively recruited persons. Correlations coefficients were calculated to identify demographic and psychosocial factors associated with interest in I-PrEP. Qualitative interviews were analyzed using concept-driven and subsequent data-driven coding. Most surveyed participants expressed an interest in I-PrEP. Quantitatively, only being interested in other HIV prevention measures was associated with interest in I-PrEP. Qualitatively, most participants preferred I-PrEP to O-PrEP and remained interested in I-PrEP despite barriers such as the somewhat invasive nature of the procedure and potential side effects of I-PrEP. Interest in I-PrEP was driven by the possibility of avoiding sexual or HIV stigma. Access to healthcare and altruism-such as assisting in the development of new HIV prevention methods-positively impacted willingness to participate in clinical trials. With I-PrEP favored by most participants, it is potentially a critical tool to prevent HIV infection among MSM & TGP in sub-Saharan Africa, with the mitigation of stigma as a major advance. Recruitment of MSM & TGP in biobehavioral clinical trials seems feasible, with altruistic reasons and receiving I-PrEP and free medical care as major motivators.
Incidence of Suicide Among Melanoma and Non-Keratinocyte Skin Cancer Patients in the US, 2000-2020
Chen ML, Rezaei SJ, Kim J, Rodriguez C, Swetter SM, O'Hara R and Linos E
Mapping recurrent mosaic copy number variation in human neurons
Sun C, Kathuria K, Emery SB, Kim B, Burbulis IE, Shin JH, , Weinberger DR, Moran JV, Kidd JM, Mills RE and McConnell MJ
When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, "CNV neurons"), but previous analyses of CNV neurons are limited by relatively small sample sizes. Here, we develop an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We apply this approach to 2,125 frontal cortical neurons from a neurotypical human brain. SCOVAL identifies 226 CNV neurons, which include a subclass of 65 CNV neurons with highly aberrant karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we find that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contain fewer, but longer, genes.
Association Between Clozapine Exposure and Risk of Hematologic Malignancies in Veterans With Schizophrenia
Brainerd DR, Alexander B, Tague MJ and Lund BC
The objective of this study was to examine the relationship between clozapine use and hematologic malignancies, using national administrative data from the United States Veterans Health Administration (VHA). This case-control study of veterans with schizophrenia matched cases with incident hematologic malignancy to 10 controls without hematologic malignancy by gender, age, and time since first schizophrenia diagnosis from October 1999, the beginning of VHA data archives, to June 2022. Schizophrenia diagnoses were identified using , code 295.x and codes F20.x and F25.x from inpatient hospitalization and outpatient encounter data. Additional inclusion criteria were age 18-85 years, no prior history of malignancy, and at least 1 year of antipsychotic exposure. Clozapine exposure was assessed using 3 metrics: any exposure, years of exposure, and cumulative defined daily doses (DDD). Conditional multivariable logistic regression was used to adjust for nonmatched confounding variables. A total of 2,306 veterans with schizophrenia were identified with an incident diagnosis of hematologic malignancy and matched to 23,043 controls. Any prior clozapine exposure was more commonly observed among cases (5.3%) than controls (4.1%) and was significantly different after adjustment (odds ratio [OR], 1.31; 95% CI, 1.08-1.60). Risk was dose-dependent, where cumulative clozapine exposures from 3,000 to 4,999 DDD (OR, 1.78; 95% CI, 1.13-2.79) and ≥5,000 DDD (OR, 1.81; 95% CI, 1.24-2.64) were significantly associated with malignancy risk. Similarly, clozapine exposure of 5 or more years was associated with malignancy risk (OR, 1.88; 95% CI, 1.43-2.47). Consistent with prior report, this study observed an increased risk of hematologic malignancy associated with clozapine exposure. These findings suggest patients receiving clozapine use, particularly those with long-term use, should be closely monitored for hematologic malignancy.
Incorporating the Distress Thermometer into preoperative vital signs in patients undergoing ambulatory oncology surgery: a pilot feasibility study
Majumdar JR, Assel M, Dannaoui A, Fatata-Haim A, Fromkin J, Nelson C, Laudone V and Carlsson SV
Despite the extensive literature supporting distress screening at relevant transitions of care, the implementation of distress screening remains limited in ambulatory surgery settings. Our multidisciplinary team completed a pilot study to assess the feasibility and acceptability of including a standardized psychosocial assessment, the Distress Thermometer (DT), with the collection of admission vital signs by Patient Care Technicians (PCTs) in patients undergoing oncology surgery.
Trajectories and influencing factors of social anxiety in postoperative breast cancer patients
Wang S, Hua Y, Zhang Y, Guo D and Tian L
Social anxiety among postoperative breast cancer patients is a prevalent concern, with its intensity fluctuating throughout the course of treatment. The study aims to describe the trajectory of social anxiety in postoperative breast cancer patients, explore the influencing factors, and provide theoretical support for the construction of future intervention programs.
Pediatric Cancer Communication on Twitter: Natural Language Processing and Qualitative Content Analysis
Lau N, Zhao X, O'Daffer A, Weissman H and Barton K
During the COVID-19 pandemic, Twitter (recently rebranded as "X") was the most widely used social media platform with over 2 million cancer-related tweets. The increasing use of social media among patients and family members, providers, and organizations has allowed for novel methods of studying cancer communication.
The clinical characteristic of catathrenia: a new look at an old issue-a systematic review of existing literature
Blaszczyk B, Wichniak A, Wieckiewcz M, Brzecka A, Nowacki D, Michalek-Zrabkowska M, Lachowicz G, Mazur G and Martynowicz H
The International Classification of Sleep Disorders categorized catathrenia as a respiratory disorder, but there are doubts whether episodes appear during rapid eye movement (REM) sleep or the non-rapid eye movement (NREM), their duration, and symptoms. The main objectives were to identify the most common features and relations of catathrenia.
Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer
Xie H, Ding C, Li Q, Sheng W, Xu J, Feng R and Cheng H
Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD.
ZNF692 promotes the migration and response to immunotherapy of clear cell renal cell carcinoma cells by targeting metabolic pathway
Liu Y, Zeng D and Gao Y
Clear cell renal cell carcinoma (ccRCC), with high mortality and poor prognosis, is the most common type of renal malignancy. It is necessary to identify new biomarkers that can serve as indicators for the detection of ccRCC at its early stages. In this study, we analyzed the role of classical zinc finger protein 692 (ZNF692) in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and Single Cell Portal and immunohistochemical (IHC) staining of a tissue-microarray, and analyzed the function of ZNF692 in ccRCC cells. The analyses indicated that ZNF692 was upregulated in ccRCC samples compared with normal or paracancerous control samples (P < 0.001) and that the expression of this gene was linked to poor overall survival (HR = 2.1, P < 0.0001). The knockdown of ZNF692 inhibited the proliferation and migration of ccRCC cells by target GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2), and transmembrane 9 superfamily member 2 (TM9SF2)). T, B, proximal, and collecting tubule cells are the dominant cell types in normal kidney tissue where ZNF692 is expressed. In addition, immune checkpoint blockade (ICB) therapy dramatically changed the expression patterns of ZNF692. Collectively, these data indicate that ZNF692 may serve as prognosis, and as a potential indicator of the response to ICB therapy, a possibility needs to be verified by a case‒control study.
Time-varying living arrangements and suicide death in the general population sample: 14-year causal survival analysis via pooled logistic regression
Narita Z, Shinozaki T, Goto A, Hori H, Kim Y, Wilcox HC, Inoue M, Tsugane S and Sawada N
While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches.
Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile
Nussbaumer G, Benesch M, Grabovska Y, Mackay A, Castel D, Grill J, Alonso MM, Antonelli M, Bailey S, Baugh JN, Biassoni V, Blattner Johnson M, Broniscer A, Carai A, Colafati GS, Colditz N, Corbacioglu S, Crampsie S, Entz-Werle N, Eyrich M, Friker LL, Frühwald MC, Garrè ML, Gerber NU, Giangaspero F, Gil-da-Costa MJ, Graf N, Hargrave D, Hauser P, Herrlinger U, Hoffmann M, Hulleman E, Izquierdo E, Jacobs S, Karremann M, Kattamis A, Kebudi R, Kortmann RD, Kwiecien R, Massimino M, Mastronuzzi A, Miele E, Morana G, Noack CM, Pentikainen V, Perwein T, Pfister SM, Pietsch T, Roka K, Rossi S, Rutkowski S, Schiavello E, Seidel C, Štěrba J, Sturm D, Sumerauer D, Tacke A, Temelso S, Valentini C, van Vuurden D, Varlet P, Veldhuijzen van Zanten SEM, Vinci M, von Bueren AO, Warmuth-Metz M, Wesseling P, Wiese M, Wolff JEA, Zamecnik J, Morales La Madrid A, Bison B, Gielen GH, Jones DTW, Jones C and Kramm CM
The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet.
Understanding Young Adult Cancer Survivors' Engagement with Cancer Storylines in Entertainment Media Narratives
Collins MKR, Lazard AJ, Dillman Carpentier F, Comello ML, Benedict C, Kent EE and Yu C
Some young adult cancer survivors (YACS; ages 18-39) struggle to incorporate their cancer experiences into their identities. Using stories, or narratives, is a new approach that could help YACS to integrate cancer and their identity. These stories offer opportunities to experience perspectives outside of oneself, which can build validation and self-compassion. However, little is known about whether stories about cancer (i.e., the threat itself) are beneficial. YACS completed an online survey about their engagement with cancer storylines in entertainment media narratives (e.g., books, movies, and television shows). They also described their reactions to encountering these storylines in entertainment media. Participants ( = 108) were primarily White. Participants who sought cancer storylines reported a more positive impact of cancer on their sense of purpose and identity. Among YACS who had completed treatment, cancer storylines were sought after treatment more than during treatment. In addition, compared with their peers, participants who identified as Black reported greater cancer storyline seeking both during and after treatment. Nearly half of participants ( = 45, 47.4%) described reactions to cancer-related storylines as positive or mixed, primarily owing to feelings of inspiration or validation. Consuming cancer storylines can offer some benefits for YACS, especially among those finished with treatment and those who identify as Black. However, not all YACS responded positively, so future research should investigate which YACS could benefit most from cancer-related storylines. Nonetheless, entertainment media narratives represent a novel approach to supporting YACS' integration of cancer into their identity.
Evaluating follow-up rates in cancer screening interventions among emergency department patients
Mondal T, Hernandez-Romero B, Wood N, Adler D and Abar B
Prevalence and associated factors of psychiatric comorbidities in epilepsy in the Casablanca-Settat region of Morocco: A cross-sectional study
Hajji EB, Traore B, Hassoune S, Khoubila A, Bellakhdar S, Rafai MA and Lakhdar A
To determine the estimated prevalence of anxiety, depression, and anxiety-depression syndrome (ADS) and to identify the associated factors in Moroccan people with epilepsy (PWE).
An Immersive Virtual Reality Intervention for Preoperative Anxiety and Distress Among Adults Undergoing Oncological Surgery: Protocol for a 3-Phase Development and Feasibility Trial
El-Gabalawy R, Sommer JL, Hebbard P, Reynolds K, Logan GS, Smith MSD, Mutter TC, Mutch WA, Mota N, Proulx C, Gagnon Shaigetz V, Maples-Keller JL, Arora RC, Perrin D, Benedictson J and Jacobsohn E
Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment.
Health insurance among survivors of childhood cancer following affordable care act implementation
Kirchhoff AC, Waters AR, Liu Q, Ji X, Yasui Y, Yabroff KR, Conti RM, Huang IC, Henderson T, Leisenring WM, Armstrong GT, Nathan PC and Park ER
The Affordable Care Act (ACA) increased private non-employer health insurance options, expanded Medicaid eligibility, and provided pre-existing health conditions protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre/post-ACA implementation.
Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015
Depond CC, Zouaoui S, Darlix A, Rigau V, Mathieu-Daudé H, Bauchet F, Khettab M, Trétarre B, Figarella-Branger D, Taillandier L, Boetto J, Pallud J, Zemmoura I, Roche PH, Bauchet L, , and
Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres.
Comparative effectiveness of remote digital gamified and group CBT skills training interventions for anxiety and depression among college students: Results of a three-arm randomised controlled trial
Bantjes J, Hunt X, Cuijpers P, Kazdin AE, Kennedy CJ, Luedtke A, Malenica I, Petukhova M, Sampson N, Zainal NH, Davids C, Dunn-Coetzee M, Gerber R, Stein DJ and Kessler RC
Digital interventions can enhance access to healthcare in under-resourced settings. However, guided digital interventions may be costly for low- and middle-income countries, despite their effectiveness. In this randomised control trial, we evaluated the effectiveness of two digital interventions designed to address this issue: (1) a Cognitive Behavioral Therapy Skills Training (CST) intervention that increased scalability by using remote online group administration; and (2) the SuperBetter gamified self-guided CBT skills training app, which uses other participants rather than paid staff as guides. The study was implemented among anxious and/or depressed South African undergraduates (n = 371) randomised with equal allocation to Remote Group CST, SuperBetter, or a MoodFlow mood monitoring control. Symptoms were assessed with the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Intention-to-treat analysis found effect sizes at the high end of prior digital intervention trials, including significantly higher adjusted risk differences (ARD; primary outcome) in joint anxiety/depression remission at 3-months and 6-months for Remote Group CST (ARD = 23.3-18.9%, p = 0.001-0.035) and SuperBetter (ARD = 12.7-22.2%, p = 0.047-0.006) than MoodFlow and mean combined PHQ-9/GAD-7 scores (secondary outcome) significantly lower for Remote Group CST and SuperBetter than MoodFlow. These results illustrate how innovative delivery methods can increase the scalability of standard one-on-one guided digital interventions. PREREGISTRATION INTERNATIONAL STANDARD RANDOMISED CONTROLLED TRIAL NUMBER (ISRTCN) SUBMISSION #: 47,089,643.
End-of-Life Care of Persons with Alzheimer's Disease and Other Dementias
Jan D and Kim KY
End-of-life (EOL) care has been a common option for patients with terminal medical conditions such as cancers. However, the utilization of EOL care in Alzheimer disease and other dementing conditions have become available relatively recently. As the end-stage dementia approaches, the clinicians and caregivers become faced with numerous clinical challenges-delirium, neuropbehavioral symptoms, the patient's inability to communicate pain and associated discomfort, food refusal, and so on. In addition to providing quality clinical care to the EOL patients, clinicians should pay special attention to their families, assuring that their loved ones will receive supportive measures to improve quality of life (QOL).
A comprehensive AI model development framework for consistent Gleason grading
Huo X, Ong KH, Lau KW, Gole L, Young DM, Tan CL, Zhu X, Zhang C, Zhang Y, Li L, Han H, Lu H, Zhang J, Hou J, Zhao H, Gan H, Yin L, Wang X, Chen X, Lv H, Cao H, Yu X, Shi Y, Huang Z, Marini G, Xu J, Liu B, Chen B, Wang Q, Gui K, Shi W, Sun Y, Chen W, Cao D, Sanders SJ, Lee HK, Hue SS, Yu W and Tan SY
Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability.
Expression of truncated products at the 5'-terminal region of RIPK2 and evolutive aspects that support their biological importance
Villagra UMM, da Cunha BR, Polachini GM, Henrique T, Stefanini ACB, de Castro TB, da Silva CHTP, Feitosa OA, Fukuyama EE, López RVM, Dias-Neto E, Nunes FD, Severino P and Tajara EH
Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protein are frequent in tumors, and that RIP-2 modulates immune and inflammatory responses, we investigated alternative splicing events that result in partial deletions of the kinase domain at the N-terminus of RIP-2. We also investigated the structure and expression of the RIPK2 truncated variants and isoforms in different environments. In addition, we searched data throughout Supraprimates evolution that could support the biological importance of RIPK2 alternatively spliced products. We observed that human variants and isoforms were differentially regulated following temperature stress, and that the truncated transcript was more expressed than the long transcript in tumor samples. The inverse was found for the longer protein isoform. The truncated variant was also detected in chimpanzee, gorilla, hare, pika, mouse, rat and tree shrew. The fact that the same variant has been preserved in mammals with divergence times up to 70 million years raises the hypothesis that it may have a functional significance.
Varenicline for E-Cigarette Cessation in Adults: A Preliminary Placebo-Controlled Randomized Trial
Fucito LM, Baldassarri SR, Baker NL, Palmer AM, O'Malley SS, Carpenter MJ, Krishnan-Sarin S, Gray KM and Toll BA
2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis
Iihara H, Abe M, Wada M, Iino K, Akechi T, Imamura CK, Okuyama A, Ozawa K, Kim YI, Sasaki H, Satomi E, Takeda M, Tanaka R, Nakajima TE, Nakamura N, Nishimura J, Noda M, Hayashi K, Higashi T, Boku N, Matsumoto K, Matsumoto Y, Okita K, Yamamoto N and Aogi K
The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens.
Factors associated with psychological distress during genetic counseling in high-risk women with breast cancer in Turkey
Anuk D, Tuncer SB, Özkan M and Yazıcı H
This study aims to shed light on the rather neglected area of research of psychological distress in women facing genetic counselling in Turkey, where few institutions providing such counselling exist.
Predictors of somatic symptoms during the COVID-19 pandemic: a national longitudinal survey in Japan
Sugawara N, Tabuchi T, Tokumitsu K and Yasui-Furukori N
The COVID-19 pandemic has highlighted the long-term consequences of SARS-CoV-2 infection, termed long COVID. However, in the absence of comparative groups, the differentiation of disease progression remains difficult, as COVID-19 symptoms become indistinguishable from symptoms originating from alternative etiologies. This study aimed to longitudinally investigate the association between COVID-19 exposure and the somatic symptoms in the Japanese general population.
Increased levels of GM-CSF and CXCL10 and low CD8 memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people
Poisson J, El-Sissy C, Serret-Larmande A, Smith N, Lebraud M, Augy JL, Conti C, Gonnin C, Planquette B, Arlet JB, Hermann B, Charbit B, Pastre J, Devaux F, Ladavière C, Lim L, Ober P, Cannovas J, Biard L, Gulczynski MC, Blumenthal N, Péré H, Knosp C, Gey A, Benhamouda N, Murris J, Veyer D, Tartour E, Diehl JL, Duffy D, Paillaud E and Granier C
Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8 T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity.
Design and rationale of the Botswana Smoking Abstinence Reinforcement Trial: a protocol for a stepped-wedge cluster randomized trial
Bada F, Mansfield ME, Okui L, Montebatsi M, DiClemente C, Tapera R, Ikgopoleng K, Mokonopi S, Magidson JF, Onukwugha E, Ndwapi N, Himelhoch S, Mbongwe B and Charurat M
With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors associated with leading causes of death among people living with HIV/AIDS (PLWH), such as tobacco smoking, has increased. Tobacco use is highly prevalent among PLWH, especially in southern Africa, where HIV is heavily concentrated, and many people who smoke would like to quit but are unable to do so without assistance. SBIRT (Screening, Brief Intervention and Referral to Treatment) is a well-established evidence-based approach successful at supporting smoking cessation in a variety of settings. Varenicline is efficacious in supporting smoking cessation. We intend to assess the effectiveness of SBIRT and varenicline on smoking cessation among PLWH in Botswana and the effectiveness of our implementation.
Quercetin Ameliorates Myocardial Injury in Diabetic Rats by Regulating Autophagy and Apoptosis through AMPK/mTOR Signaling Pathway
Chen YF, Qiu Q, Wang L, Li XR, Zhou S, Wang H, Jiang WD, Geng JY, Qin-Gao , Tang B, Wang HJ and Kang PF
A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet . Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group and . Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.
Financial toxicity and health-related quality of life in long-term survivors of acute promyelocytic leukaemia
Sparano F, Voso MT, Venditti A, Giesinger JM, Baldi T, Breccia M, Fazi P, Vignetti M and Efficace F
We aimed to investigate the association between financial toxicity (FT) and the health-related quality of life profile of long-term survivors of acute promyelocytic leukaemia (APL) treated within a universal healthcare system.
Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants
Rahman MS, Harrison E, Biggs H, Seikus C, Elliott P, Breen G, Kingston N, Bradley JR, Hill SM, Tom BDM and Chinnery PF
A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.
Japanese value set for the EORTC QLU-C10D: A multi-attribute utility instrument based on the EORTC QLQ-C30 cancer-specific quality-of-life questionnaire
Shiroiwa T, King MT, Norman R, Müller F, Campbell R, Kemmler G, Murata T, Shimozuma K and Fukuda T
This study aimed to develop a Japanese value set for the EORTC QLU-C10D, a multi-attribute utility measure derived from the cancer-specific health-related quality-of-life (HRQL) questionnaire, the EORTC QLQ-C30. The QLU-C10D contains ten HRQL dimensions: physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems.
Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome
Vinnakota JM, Biavasco F, Schwabenland M, Chhatbar C, Adams RC, Erny D, Duquesne S, El Khawanky N, Schmidt D, Fetsch V, Zähringer A, Salié H, Athanassopoulos D, Braun LM, Javorniczky NR, Ho JNHG, Kierdorf K, Marks R, Wäsch R, Simonetta F, Andrieux G, Pfeifer D, Monaco G, Capitini C, Fry TJ, Blank T, Blazar BR, Wagner E, Theobald M, Sommer C, Stelljes M, Reicherts C, Jeibmann A, Schittenhelm J, Monoranu CM, Rosenwald A, Kortüm M, Rasche L, Einsele H, Meyer PT, Brumberg J, Völkl S, Mackensen A, Coras R, von Bergwelt-Baildon M, Albert NL, Bartos LM, Brendel M, Holzgreve A, Mack M, Boerries M, Mackall CL, Duyster J, Henneke P, Priller J, Köhler N, Strübing F, Bengsch B, Ruella M, Subklewe M, von Baumgarten L, Gill S, Prinz M and Zeiser R
Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. Here we examined the role of microglia using mouse models and cohorts of individuals with ICANS. CD19-directed CAR (CAR19) T cell transfer in B cell lymphoma-bearing mice caused microglia activation and neurocognitive deficits. The TGFβ-activated kinase-1 (TAK1)-NF-κB-p38 MAPK pathway was activated in microglia after CAR19 T cell transfer. Pharmacological TAK1 inhibition or genetic Tak1 deletion in microglia using Cx3cr1:Tak1 mice resulted in reduced microglia activation and improved neurocognitive activity. TAK1 inhibition allowed for potent CAR19-induced antilymphoma effects. Individuals with ICANS exhibited microglia activation in vivo when studied by translocator protein positron emission tomography, and imaging mass cytometry revealed a shift from resting to activated microglia. In summary, we prove a role for microglia in ICANS pathophysiology, identify the TAK1-NF-κB-p38 MAPK axis as a pathogenic signaling pathway and provide a rationale to test TAK1 inhibition in a clinical trial for ICANS prevention after CAR19 T cell-based cancer immunotherapy.
Top Ten Tips Palliative Care Clinicians Should Know About the Psychiatric Manifestations of Nonpsychiatric Serious Illness and Treatments
Robbins-Welty GA, Riordan PA, Shalev D, Chammas D, Noufi P, Brenner KO, Briscoe J, Rosa WE and Webb JA
Mental health issues are widespread and significant among individuals with serious illness. Among patients receiving palliative care (PC), psychiatric comorbidities are common and impact patient quality of life. Despite their prevalence, PC clinicians face challenges in effectively addressing the intricate relationship between medical and psychiatric disorders due to their complex, intertwined and bidirectionally influential nature. This article, created collaboratively with a team of psychiatric-palliative care experts, is the second in a two-part series examining the bidirectional relationship between medical and psychiatric illness in PC. This article explores 10 prevalent psychiatric manifestations associated with severe illness and its treatment. Building upon the first article, which focused on 10 common physical manifestations of psychiatric illness among patients receiving PC, these two articles advocate for an integrated approach to PC that prioritizes mental and emotional wellbeing across the continuum of serious illness.
The glucose transporter GLUT12, a new actor in obesity and cancer
Burgos M, Gil-Iturbe E, Idoate-Bayón A, Castilla-Madrigal R, Moreno-Aliaga MJ and Lostao MP
Obesity constitutes a global health epidemic which worsens the main leading death causes such as type 2 diabetes, cardiovascular diseases, and cancer. Changes in the metabolism in patients with obesity frequently lead to insulin resistance, along with hyperglycemia, dyslipidemia and low-grade inflammation, favoring a more aggressive tumor microenvironment. One of the hallmarks of cancer is the reprogramming of the energy metabolism, in which tumor cells change oxidative phosphorylation to aerobic glycolysis or "Warburg effect". Aerobic glycolysis is faster than oxidative phosphorylation, but less efficient in terms of ATP production. To obtain sufficient ATP, tumor cells increase glucose uptake by the glucose transporters of the GLUT/SLC2 family. The human glucose transporter GLUT12 was isolated from the breast cancer cell line MCF7. It is expressed in adipose tissue, skeletal muscle and small intestine, where insulin promotes its translocation to the plasma membrane. Moreover, GLUT12 over-expression in mice increases the whole-body insulin sensitivity. Thus, GLUT12 has been proposed as a second insulin-responsive glucose transporter. In obesity, GLUT12 is downregulated and does not respond to insulin. In contrast, GLUT12 is overexpressed in human solid tumors such as breast, prostate, gastric, liver and colon. High glucose concentration, insulin, and hypoxia upregulate GLUT12 both in adipocytes and tumor cells. Inhibition of GLUT12 mediated Warburg effect suppresses proliferation, migration, and invasion of cancer cells and xenografted tumors. This review summarizes the up-to-date information about GLUT12 physiological role and its implication in obesity and cancer, opening new perspectives to consider this transporter as a therapeutic target.
History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products
Giguere R, Balán IC, Kutner BA, Choi SK, Tingler R, Johnson S, Macagna N, Webster J, Liu A, Chariyalertsak S, Hoesley C, Gonzales P, Ho K, Kayange N, Palanee-Phillips T, Brown E, Zemanek J, Jacobson CE, Doncel GF, Piper J, Bauermeister JA and
The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.
Psychotropic Medication Prescriptions for Home-Based Palliative Care Oncology Patients
Mohamed F, Uvais NA, Moideen S, Cp RR and Saif M
To examine the complexities of psychotropic medication prescription in home-based palliative care for oncology patients. A retrospective analysis of 125 medical records of patients receiving palliative home care for cancer was conducted at a tertiary hospital, with a specific focus on the prescription patterns of psychotropic medications. The data were collected in September 2023. Among 125 cases, the mean age was 64.4 ± 14.9 years, with 50.4% females. Breast cancer (14.4%) and lung cancer (13.6%) were the most common diagnoses. Psychotropic medication was administered to 35.2% of patients. Treatment was initiated by palliative care doctors in 75% of cases, while psychiatrists handled 25%. Medication selection was predominantly symptom driven (63%), with anxiety prompting benzodiazepine prescriptions in 50% of cases, depression resulting in antidepressant use in 22%, and psychosis leading to antipsychotic treatment in 18%. Specific diagnoses were the target in only 36% of prescriptions, with delirium (27%) being the most prevalent, followed by depression and bipolar disorder. Benzodiazepines were the most commonly prescribed class of medications (56.8%), with clonazepam being the most prevalent (40.9%), followed by alprazolam and lorazepam (15.9%). Atypical antipsychotics made up 43.1% of prescriptions, with quetiapine being the most frequently prescribed (34%), along with olanzapine and risperidone (11%). Antidepressants accounted for 31.8% of prescriptions, including selective serotonin reuptake inhibitors at 18% and mirtazapine and amitriptyline at 6% each. Haloperidol, a typical antipsychotic, was prescribed in 13.6% of cases. Polypharmacy was observed in 35.6% of patients. In palliative home care, psychotropic medications are frequently prescribed by palliative doctors primarily for symptom management, with limited psychiatric consultations and challenges in accessing psychological evaluations. Collaborative efforts among regional or institutional medical bodies, including psychiatrists, psychologists, palliative doctors, and social workers, are needed to establish ethical guidelines for appropriate and effective psychotropic prescription. .
Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement
Hohenschurz-Schmidt D, Cherkin D, Rice ASC, Dworkin RH, Turk DC, McDermott MP, Bair MJ, DeBar LL, Edwards RR, Evans SR, Farrar JT, Kerns RD, Rowbotham MC, Wasan AD, Cowan P, Ferguson M, Freeman R, Gewandter JS, Gilron I, Grol-Prokopczyk H, Iyengar S, Kamp C, Karp BI, Kleykamp BA, Loeser JD, Mackey S, Malamut R, McNicol E, Patel KV, Schmader K, Simon L, Steiner DJ, Veasley C and Vollert J
Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.
The microtubule targeting agent ST-401 triggers cell death in interphase and prevents the formation of polyploid giant cancer cells
Vicente JJ, Khan K, Tillinghast G, McFaline-Figueroa JL, Sancak Y and Stella N
Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells escape death in mitosis, exit mitosis and become malignant polyploid giant cancer cells (PGCC). Considering the low number of cancer cells undergoing mitosis in tumor tissues, killing them in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule (MT) assembly, preferentially kills cancer cells in interphase as opposed to mitosis, a cell death mechanism that avoids the development of PGCC. Single cell RNA sequencing identified mRNA transcripts regulated by ST-401, including mRNAs involved in ribosome and mitochondrial functions. Accordingly, ST-401 induces a transient integrated stress response, reduces energy metabolism, and promotes mitochondria fission. This cell response may underly death in interphase and avoid the development of PGCC. Considering that ST-401 is a brain-penetrant MTA, we validated these results in glioblastoma cell lines and found that ST-401 also reduces energy metabolism and promotes mitochondria fission in GBM sensitive lines. Thus, brain-penetrant mild inhibitors of MT assembly, such as ST-401, that induce death in interphase through a previously unanticipated antitumor mechanism represent a potentially transformative new class of therapeutics for the treatment of GBM.
Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia
Feng S, Huang Y, Li H, Zhou S, Ning Y, Han W, Zhang Z, Liu C, Li J, Zhong L, Wu K and Wu F
Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown.
Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update
Bower JE, Lacchetti C, Alici Y, Barton DL, Bruner D, Canin BE, Escalante CP, Ganz PA, Garland SN, Gupta S, Jim H, Ligibel JA, Loh KP, Peppone L, Tripathy D, Yennu S, Zick S and Mustian K
To update the ASCO guideline on the management of cancer-related fatigue (CRF) in adult survivors of cancer.
Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023
Kobayashi M, Kako J, Iba A, Okuyama A, Ozawa K, Abe M, Wada M, Akechi T, Iihara H, Imamura CK, Kim YI, Sasaki H, Satomi E, Takeda M, Tanaka R, Nakajima TE, Nakamura N, Nishimura J, Noda M, Hayashi K, Higashi T, Boku N, Matsumoto K, Matsumoto Y, Okita K, Yamamoto N, Aogi K and Iino K
Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer.
The role of area deprivation index in health care disruptions among cancer survivors during the SARS-CoV-2 pandemic
Wagner RW, Natori A, Prinsloo S, Otto AK, Saez-Clarke E, Ochoa JM, Tworoger SS, Ulrich CM, Hathaway CA, Ahmed S, McQuade JL, Peoples AR, Antoni MH, Penedo FJ and Cohen L
To examine the associations between demographic/medical and geographic factors with follow-up medical care and health-related quality of life (HRQoL) among cancer survivors during the SARS-CoV-2 pandemic.
Top Ten Tips Palliative Care Clinicians Should Know About the Physical Manifestations of Psychiatric Illness and Treatment
Robbins-Welty GA, Shalev D, Riordan PA, Noufi P, Webb JA, Brenner KO, Rosa WE and Chammas D
Addressing the psychiatric aspects of serious illness in palliative care (PC) is crucial to both care delivery and outcomes. Psychiatric comorbidities are common among patients with PC needs and can significantly impact their total burden of symptomatic distress, overall quality of life, functional independence, and healthcare utilization. Yet, these aspects of care are often deferred to mental health consultant teams in the context of busy PC services and often limited human resources. To provide comprehensive and person-centered care, PC clinicians must understand the interplay between medical conditions and psychiatric presentations within a biopsychosocial framework to respond empathically, efficiently, and effectively. This article is the first of a two-part series developed in collaboration with a group of psychiatric-palliative care specialists. This article explores ten common physical manifestations of psychiatric illness and treatment among patients facing serious illnesses. The second article will provide pragmatic tips PC clinicians should know about the psychiatric manifestations of nonpsychiatric serious illness and treatment. Combined, these two articles support a holistic approach that PC clinicians can use to prioritize and integrate both mental and emotional well-being throughout the continuum of serious illness.
"Walk me through the final day": A thematic analysis study on the family caregiver experience of the Medical Assistance in Dying procedure day
Nissim R, Chu P, Stere A, Tong E, An E, Selby D, Bean S, Isenberg-Grzeda E, Rodin G, Li M and Hales S
Legalization of assisted dying is progressively expanding worldwide. In Canada, the Medical Assistance in Dying Act became law in 2016. As assisted dying regulations evolve worldwide, comprehending its subjective impact and broader consequences, especially on family members, becomes pivotal for shaping practice, policy, and training.
Emotional Distress, Cognitive Complaints, and Care Needs among Advanced Cancer Survivors Treated with Immune Checkpoint Blockade: A Mixed-Method Study
Vanlaer N, Dirven I, Neyns B and Rogiers A
There is a need for a better understanding of survivorship-related issues in advanced cancer survivors treated with immune checkpoint blockade (ICB). The purpose of this study was to identify survivorship-related issues, with a focus on psychological distress, cognitive complaints, physical sequelae, impact on family dynamics, and care needs in unresectable, advanced cancer survivors treated with ICB.
Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study
Boustani A, Kulbe JR, Andalibi MS, Pérez-Santiago J, Mehta SR, Ellis RJ and Fields JA
Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.
Palliative care tumor board: a narrative review and presentation of a novel conference to enhance collaboration and coordination of pain and symptom management for patients with advanced cancer
Guyer D, Steinhoff T, Maxwell AWP, Szymanski T, Shahamatdar S, Pinto M and Almhanna K
The World Health Organization endorses that palliative care has a significant impact on the outcomes of patients with cancer. Integration of palliative care into standard oncology practice has been shown to improve a variety of patient outcomes. In this article, we present our experience with the development of a palliative care tumor board.
A Systematic Review and Meta-Analysis of Endoscopic Surveillance Studies for Detecting Dysplasia in Patients With Inflammatory Bowel Disease
Virk GS, Rashad E, Chaudhry R, Moazam MM, Mahbub M, Hanif AF, Tamene Y and Tadesse L
Inflammatory bowel disease (IBD)is an extremely common gastrointestinal disorder that can give rise to dysplasia and colorectal cancer (CRC). There are various diagnostic methods but endoscopy has proved to be the best in the diagnosis, monitoring, and treatment of IBD. The objective of this review is to evaluate the efficacy of endoscopy in detecting patients with IBD. A structured search strategy on PubMed, Science Direct, and Google Scholar was used, as well as formal inclusion or exclusion, data extraction, validity assessment, and meta-analysis. RevMan 5.4 (Review Manager (RevMan) (Computer program). Version 5.4. The Cochrane Collaboration, 2020) was used for the meta-analysis, and forest plots were generated for each outcome separately. All of these studies are prospective cohorts and 11 of these are randomized controlled trials (RCTs). In IBD, both chromoendoscopy and white light endoscopy are useful in detecting dysplasia and neoplastic lesions. Furthermore, narrow-band imaging is a less time-consuming option for endoscopic surveillance. The meta-analysis also showed that chromoendoscopy is superior to other methods.
Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon
Bellman V
Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon's Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression, including an evaluation of its purported benefits and potential adverse effects. It provides a comprehensive examination of therapeutic strategies, dosing regimens, and barriers to ensuring responsible and equitable access. Salient issues explored include the development of ethical protocols, integration within healthcare systems, ensuring statewide availability, resolving legal ambiguities, and defining clinical standards. Oregon's pioneering role serves as a case study, highlighting the necessity of addressing regulatory, logistical, and ethical obstacles to ensure the establishment of rigorous and equitable psilocybin care models.
Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts
Stepanova OV, Fursa GA, Karsuntseva EK, Andretsova SS, Chadin AV, Voronova AD, Shishkina VS, Semkina AS, Reshetov IV and Chekhonin VP
This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.
Cancer screening research in Bangladesh: Insights from a scoping review
Chowdhury MZI, Mubin N, Mohib T, Chowdhury N, Chowdhury TF, Laskar AMH, Sultana S, Raihan M and Turin TC
This scoping review summarises the findings of research conducted on cancer screening in Bangladesh, including the prevalence, awareness, barriers, and evaluation of screening programmes, by performing a comprehensive search of electronic databases and gray literature. 25 studies that met inclusion criteria were included in the final analysis. Most of the studies were about screening for cervical cancer, were quantitative, were cross-sectional, and were conducted in hospital settings. The main challenges to screening uptake were shyness, fear, a lack of knowledge, and an inadequate understanding of the concept of screening. Visual inspection with acetic acid (VIA) was found to be a simple and cost-efficient way to detect early-stage cervical cancer. However, breast self-examination (BSE) was reported to be insufficient. Education was found to have a positive impact on cancer screening knowledge and practice, but more needs to be done to improve screening rates, such as the utilisation of media, particularly in rural areas. The results of this scoping review highlight Bangladesh's low cancer screening prevalence and uptake and suggest that targeted awareness campaigns and enhanced access to screening services are required to increase cancer screening uptake and reduce the cancer burden in Bangladesh.
Identification and Analyses of Crucial Genes Associated with Pathogenesis of Major Depressive Disorder
Li J, Ma Q and Ai M
Major depressive disorder is a debilitating mental condition that causes severe disability leading to a high fatality rate. No valid blood-based biomarkers for major depressive disorder are currently available. The purpose of this research is to investigate gene biomarkers and pathways that may be linked to major depressive disorder pathogenesis.
Project Respect: experiences of seriously ill LGBTQ+ patients and partners with their health care providers
Stein GL, Berkman C, Acquaviva K, Woody I, Godfrey D, Javier NM, O'Mahony S, González-Rivera C, Maingi S, Candrian C and Rosa WE
Discrimination against lesbian, gay, bisexual, transgender, and queer (LGBTQ+) persons in health care creates barriers to serious illness care, including patients avoiding or delaying necessary care, providers disrespecting wishes of surrogates, and adverse outcomes for patients and families. A cross-sectional mixed-methods study using an online survey was used to determine the extent to which LGBTQ+ patients and spouses, partners, and widows experienced disrespectful or inadequate care due to sexual orientation or gender identity. A total of 290 LGBTQ+ patients and partners reported high levels of disrespectful and inadequate care, including 35.2% stating their provider was insensitive to them because of their identity; 30% reporting their provider was unaware of LGBTQ+ health needs; 23.1% feeling judged; 20.7% experiencing rudeness; 20.3% stating providers did not use their correct pronouns; and 19.7% reporting their treatment decisions were disregarded. Black and Hispanic patients were 2-4 times more likely than non-Hispanic White patients to report discrimination. This study demonstrated high levels of disrespectful and inadequate care towards patients and partners due to being LGBTQ+, which was especially problematic for Black and Hispanic patients and those living in politically conservative regions. Recommendations include federal and state civil rights laws to prohibit LGBTQ+ discrimination and institutional practices to address discrimination, including cultural sensitivity training for staff.
Eye Movement Desensitization and Reprocessing (EMDR) treatment in the medical setting: a systematic review
Driessen HPA, Morsink S, Busschbach JJV, Hoogendijk WJG and Kranenburg LW
Literature points towards the potential benefits of the application of Eye Movement and Desensitization Processing (EMDR)-therapy for patients in the medical setting, with cancer and pain being among the domains it is applied to. The field of applying EMDR-therapy for patients treated in the medical setting has evolved to such an extent that it may be challenging to get a comprehensive overview. This systematic literature review aims to evaluate the use and effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) therapy in patients treated in the medical setting. We performed a literature search following the PRISMA guidelines. Studies were included if the effectiveness of EMDR-therapy was assessed in adult patients treated in a medical setting. Excluded were patients exclusively suffering from a mental health disorder, without somatic comorbidity. A risk of bias analysis was performed. This review was registered on PROSPERO (CRD42022325238). Eighty-seven studies, of which 26 (pilot)-RCTs were included and categorized in 14 medical domains. Additionally, three studies focusing on persistent physical complaints were included. Most evidence exists for its application in the fields of oncology, pain, and neurology. The overall appraisal of these studies showed at least moderate to high risks of bias. EMDR demonstrated effectiveness in reducing symptoms in 85 out of 87 studies. Notably, the occurrence of adverse events was rarely mentioned. Overall, outcomes seem to show beneficial effects of EMDR on reducing psychological and physical symptoms in patients treated in a medical setting. Due to the heterogeneity of reported outcomes, effect sizes could not be pooled. Due to the high risk of bias of the included studies, our results should be interpreted with caution and further controlled high-quality research is needed.
Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability
Schmilovich Z, Bourque VR, Douard E, Huguet G, Poulain C, Ross JP, Alipour P, Castonguay CÉ, Younis N, Jean-Louis M, Saci Z, Pausova Z, Paus T, Schuman G, Porteous D, Davies G, Redmond P, Harris SE, Deary IJ, Whalley H, Hayward C, Dion PA, Jacquemont S and Rouleau GA
Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer susceptibility for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD susceptibility, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.
A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression
Koneczny I, Mané-Damas M, Zong S, De Haas S, Huda S, van Kruining D, Damoiseaux J, De Rosa A, Maestri M, Guida M, Molenaar P, Van Damme P, Fichtenbaum A, Perkmann T, De Baets M, Lazaridis K, Zouvelou V, Tzartos S, Ricciardi R, Losen M and Martinez-Martinez P
Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.
Study protocol for measuring stigmatization in persistent tic disorders: development and validation of the Tourette discrimination-stigmatization scale
Martindale JM, Ringheanu VM, Pring KA, Norona S, Wiseman K, Strowd RE, Chapman L, Rigdon J, Rapp SR, Storch EA, Ip E and Mink JW
Persistent Tic Disorders such as Tourette Syndrome are common neurodevelopmental disorders that are highly stigmatized. Many individuals with Persistent Tic Disorders experience peer rejection, loneliness, and self-stigma. Experiencing stigmatization during childhood can influence the persistence of moderate-to-severe tics later in life. Additionally, these factors have been associated with increased suicidal ideation, suicide attempts, and psychiatric symptom severity. There is a need for interventions to reduce stigma and stigmatization in Persistent Tic Disorders. Before developing cost-effective interventions to mitigate stigma's profound downstream health impacts, a reliable measure of stigmatization must be created. The overarching goal of this research is to develop and validate the Tourette Discrimination-Stigmatization (TD-STIGMA) Scale.
Evaluation of IFNAR2 and TYK2 transcripts' prognostic role in COVID-19 patients: a retrospective study
Razavi A, Raei M, Hatami Y, Chokami GS, Goudarzi Y, Ghasemian R, Alizadeh-Navaei R, Yarmohammadi H, Soltanipur M, Tabarestani M, Valadan R, Meshkinfam Haghighi F, Tarsi AK and Razavi B
This study aimed to investigate the possible prognostic significance of interferon alpha-beta receptor subunit 2 (IFNAR2) and tyrosine kinase 2 (TYK2) expressions.
Biobehavioral approach to distinguishing panic symptoms from medical illness
Tunnell NC, Corner SE, Roque AD, Kroll JL, Ritz T and Meuret AE
Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.
Transformation of IDH-wildtype glioblastoma to gliosarcoma with features of osteosarcoma
Sobczyk P, Sobstyl M, Acewicz A, Rosa J, Grabiec M and Grajkowska W
Gliosarcoma (GS) is a rare variant of IDH-wildtype glioblastoma. It is classified as grade 4 in the latest WHO CNS classification of both glial and mesenchymal components. Gliosarcoma may arise de novo or secondary from glioblastoma. It occurs in up to 2% of patients diagnosed with glioblastoma. We present a case report of a 51-year-old patient who was initially diagnosed with glioblastoma multiforme, which transformed into secondary gliosarcoma with an osteosarcoma component 16 months after the initial diagnosis. We believe that increasing reporting of secondary gliosarcoma (sGS) will be helpful in understanding, diagnosing and providing more effective treatment for this cancer.
Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells
Dimapasoc M, Moran JA, Cole SW, Ranjan A, Hourani R, Kim JT, Wender PA, Marsden MD and Zack JA
Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way.
Prevalence of depression and anxiety among newly diagnosed cancer patients: a single centre experience in the Middle East
Hassan MA, Mahmoud AE, Kalash S, Kadi T, Bakhos N, Zeidane RA, Amhaz G, Bizri M and Assi HI
Failure to identify and treat depression and anxiety affecting 10% of patients with cancer, increases the disease burden. This study aimed to assess the psychological well-being of newly diagnosed patients in a tertiary healthcare centre in Lebanon. In this cross-sectional study, data were collected for 187 adult patients, from medical records and interviews using standardised questionnaires (Personal health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7). Karnofsky performance status was also assessed, and incidence was calculated using descriptive statistics, chi-square, and -tests. The rates of moderate or severe anxiety, minimal anxiety, mild depression, moderate or severe depression, and suicidality are 14.9%, 35.6%, 40.7% 22.7% and 6.2%, respectively. Participants with a past history of seeking help from mental health services (OR: 3.978, CI: (1.680-9.415), = 0.002), those developing cancer-related complications (OR: 3.039, CI: (1.187-7.777), = 0.020), and those who had an Eastern Cooperative Oncology Group of ≥2 (OR: 5.306, CI: (1.582-17.797), = 0.007) were independently associated with depression (diagnosed with PHQ-9) in multivariate logistic regression analysis. Patients with cancer exhibit higher evidence of depression and anxiety and should have a thorough psychiatric history and additional psychiatric care.
Automated radiosynthesis of [C]CPPC for in-human PET imaging applications
Jiang H, Roy P, Guo Y, Muzik O and Woodcock EA
The macrophage colony-stimulating factor 1 receptor (CSF1R) is almost exclusively expressed in microglia, representing a biomarker target for imaging of microglia availability. [C]CPPC has specific binding affinity to CSF1R and suitable kinetic properties for PET imaging of microglia. However, previous studies reported a low radiochemical yield, motivating additional research to optimize [C]CPPC radiochemistry. In this work, we report an automated radiosynthesis of [C]CPPC on a Synthra MeIPlus module with improved radiochemical yield. The final [C]CPPC product was obtained with excellent chemical/radiochemical purities and molecular activity, facilitating high-quality in-human PET imaging applications.
Data leakage in deep learning studies of translational EEG
Brookshire G, Kasper J, Blauch NM, Wu YC, Glatt R, Merrill DA, Gerrol S, Yoder KJ, Quirk C and Lucero C
A growing number of studies apply deep neural networks (DNNs) to recordings of human electroencephalography (EEG) to identify a range of disorders. In many studies, EEG recordings are split into segments, and each segment is randomly assigned to the training or test set. As a consequence, data from individual subjects appears in both the training and the test set. Could high test-set accuracy reflect data leakage from subject-specific patterns in the data, rather than patterns that identify a disease? We address this question by testing the performance of DNN classifiers using segment-based holdout (in which segments from one subject can appear in both the training and test set), and comparing this to their performance using subject-based holdout (where all segments from one subject appear exclusively in either the training set or the test set). In two datasets (one classifying Alzheimer's disease, and the other classifying epileptic seizures), we find that performance on previously-unseen subjects is strongly overestimated when models are trained using segment-based holdout. Finally, we survey the literature and find that the majority of translational DNN-EEG studies use segment-based holdout. Most published DNN-EEG studies may dramatically overestimate their classification performance on new subjects.
Role of a mental health physician in the management of oncology patients: a case vignette and the need for collaboration
Armiya'u AY and Akande Y
There is an interplay between oncology and mental health, resulting in a high prevalence of mental disorders among cancer patients. Out of the several interventions developed to target cancer specifics, collaborative care is indicated due to its efficacy. The perspective delves into the efficacy of collaborative care models, spotlighting a culturally informed strategy designed to harmonize mental and physical health interventions to bolster the overall wellbeing and resilience of individuals battling cancer. Central to our discussion is a compelling case vignette of Raliat, a patient diagnosed with ovarian cancer whose narrative exemplifies the multifaceted challenges cancer patients face, including stigma, psychological distress, and social isolation. Raliat's story illuminates the profound impact of cultural beliefs on patient experiences and the critical importance of a sensitive, holistic approach to care that respects cultural contexts. Through this lens, our analysis reveals that addressing emotional and situational stressors through collaborative care can significantly reduce oxidative stress, potentially decelerating the progression of both cancer and accompanying mental health disorders. We advocate for integrating mental health services into oncological care, drawing on the case vignette to argue for policies that facilitate such merger by employing validated collaborative care models. We conclude with a call for public education to diminish cancer stigma and improve social outcomes, emphasizing the use of a culture-informed PACER (physical, affective, cognitive, environmental, and relationship) strategy in providing comprehensive care for cancer patients and their families.
Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol
Anderson LJ, Paulsen L, Miranda G, Syrjala KL, Graf SA, Chauncey TR and Garcia JM
Hematopoietic stem cell transplantation is a common life-saving treatment for hematologic malignancies, though can lead to long-term functional impairment, fatigue, muscle atrophy, with decreased quality of life. Although traditional exercise has helped reduce these effects, it is inconsistently recommended and infrequently maintained, and most patients remain sedentary during and after treatment. There is need for alternative rehabilitation strategies, like neuromuscular electrical stimulation, that may be more amenable to the capabilities of hematopoietic stem cell transplant recipients. Patients receiving autologous HCT are being enroled in a randomized controlled trial with 1:1 (neuromuscular electrical stimulation:sham) design stratified by diagnosis and sex. Physical function, body composition, quality of life, and fatigue are assessed prior to hematopoietic stem cell transplant (prior to initiating preparatory treatment) and 24±5 days post hematopoietic stem cell transplant (Follow-up 1); physical function and quality of life are also assessed 6-months post hematopoietic stem cell transplant (Follow-up 2). The primary outcome is between-group difference in the 6-minute walk test change scores (Follow-up 1-Pre-transplant; final enrolment goal N = 23/group). We hypothesize that 1) neuromuscular electrical stimulation will attenuate hematopoietic stem cell transplant-induced adverse effects on physical function, muscle mass, quality of life, and fatigue compared to sham at Follow-up 1, and 2) Pre-transplant physical function will significantly predict fatigue and quality of life at Follow-up 2. We will also describe feasibility and acceptability of neuromuscular electrical stimulation during hematopoietic stem cell transplant. This proposal will improve rehabilitative patient care and quality of life by determining efficacy and feasibility of a currently underutilized therapeutic strategy aimed at maintaining daily function and reducing the impact of a potent and widely used cancer treatment. This trial is registered with clinicaltrials.gov (NCT04364256).
The prevalence of post-traumatic stress disorder among emergency medical services personnel in Saudi Red Crescent Authority, Riyadh, Saudi Arabia
Alanazi SZ, Abusharha A, Afsar T, Trembley JH and Razak S
Determining the prevalence of PTSD and contributing variables among (EMS) specialists was the goal of the current investigation. Furthermore, limited evidence exists regarding the application of PCL-5 for EMT practitioners, and the incidence of PTSD among different age groups and genders in Saudi Arabia.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the dura mimicking meningioma: a case report and literature review
Glinka P, Sobstyl M, Rymkiewicz G, Wierzba-Bobrowicz T, Paszkiewicz-Kozik E and Grajkowska W
MALT lymphoma of the dura is a very rare type of low-grade B-cell lymphoma. Little more than 100 cases have been reported in the literature to date. We report a 43-year-old woman who was referred to hospital because of a series of three tonic-clonic seizures on the day of admission. Neurological examination revealed confusion and aphasia. Magnetic resonance imaging (MRI) showed a contrast-enhanced, broad-based lesion along the dura in the left parieto-occipital area. The suspicion of an en plaque meningioma was raised. The tumour invaded the brain parenchyma with visible extension into the brain sulci. There was a marked brain oedema surrounding the lesion and causing the midline shift 8 mm to the right. After stabilization of neurological condition (intravenous diuretics and steroids), the operation was performed. The diagnosis of dural MALT lymphoma was established. During the pathological examination, it was especially problematic to distinguish MALT lymphoma from follicular lymphoma, but the final diagnosis was MALT lymphoma. Surgical partial removal with additional R-CVP immunochemotherapy (rituximab, cyclophosphamide, vincristine and prednisone) resulted in complete remission. The follow-up period is 1 year. Our presented case of a MALT lymphoma highlights the fact that surgical partial removal with additional immunochemotherapy is an available option in these rare intracranial tumours.
MRI detection of mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) on T1WI-CHESS
Arizono E, Tanei ZI, Iijima K, Kimura Y, Shigemoto Y, Maki H, Kusama M, Murayama K, Iwasaki M, Saito T, Saito Y, Saito K and Sato N
Mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) is a recently proposed epileptogenic entity that is difficult to detect on MRI. We present a case of MOGHE that was successfully detected on T1WI-chemical shift-selective saturation (CHESS) MRI. The clinical presentation, MRI including T1WI-CHESS, functional images, and pathology findings of a 14-year-old Japanese girl diagnosed with MOGHE are described. T1WI-CHESS revealed an abnormal high signal along the affected lesion, whereas the findings shown by the other MR sequences were less obvious; interictal fluorodeoxyglucose-positron emission tomography indicated slightly decreased accumulation in the lesion, and subtraction ictal single photon emission computed tomography co-registered to MRI showed an increased blood flow. Together these observations suggest that T1WI-CHESS may be a useful MR sequence for detecting the lesions in patients with MOGHE.
Factors influencing self-regulatory fatigue in patients undergoing chemotherapy for gynecologic cancer: a cross-sectional study
Lin C, Zhang F, Yang F, Lin Y, Tian T, Shi K, Li M and Li X
To understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factors.
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