Cancer and Psychiatry

While objective clinical structured examination (OSCE) is a worldwide recognized and effective method to assess clinical skills of undergraduate medical students, the latest Ottawa conference on the assessment of competences raised vigorous debates regarding the future and innovations of OSCE. This study aimed to provide a comprehensive view of the global research activity on OSCE over the past decades and to identify clues for its improvement. We performed a bibliometric and scientometric analysis of OSCE papers published until March 2024. We included a description of the overall scientific productivity, as well as an unsupervised analysis of the main topics and the international scientific collaborations. A total of 3,224 items were identified from the Scopus database. There was a sudden spike in publications, especially related to virtual/remote OSCE, from 2020 to 2024. We identified leading journals and countries in terms of number of publications and citations. A co-occurrence term network identified three main clusters corresponding to different topics of research in OSCE. Two connected clusters related to OSCE performance and reliability, and a third cluster on student's experience, mental health (anxiety), and perception with few connections to the two previous clusters. Finally, the United States, the United Kingdom, and Canada were identified as leading countries in terms of scientific publications and collaborations in an international scientific network involving other European countries (the Netherlands, Belgium, Italy) as well as Saudi Arabia and Australia, and revealed the lack of important collaboration with Asian countries. Various avenues for improving OSCE research have been identified: i) developing remote OSCE with comparative studies between live and remote OSCE and issuing international recommendations for sharing remote OSCE between universities and countries; ii) fostering international collaborative studies with the support of key collaborating countries; iii) investigating the relationships between student performance and anxiety.

There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems.

Ovarian cancer is the second most common gynecologic cancer in the United States and the deadliest gynecologic cancer worldwide, with a 5-year survival rate of less than 50%. Because of its vague symptoms, more than half of patients present with advanced disease and metastasis. This article reviews the epidemiology, pathogenesis, risk factors, screening, presentation, and diagnosis of ovarian cancer, in addition to providing an overview of the standard approach to treatment and novel targeted biologic therapies.

A novel histomolecular tumor of the central nervous system (CNS), the "diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)," has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis.

Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023.

Neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology.

Northwestern University's Center for Scalable Telehealth Cancer Care (STELLAR) is 1 of 4 Cancer Moonshot Telehealth Research Centers of Excellence programs funded by the National Cancer Institute to establish an evidence base for telehealth in cancer care. STELLAR is grounded in the Institute of Medicine's vision that quality cancer care includes not only disease treatment but also promotion of long-term health and quality of life (QOL). Cigarette smoking, insufficient physical activity, and overweight and obesity often co-occur and are associated with poorer treatment response, heightened recurrence risk, decreased longevity, diminished QOL, and increased treatment cost for many cancers. These risk behaviors are prevalent in cancer survivors, but their treatment is not routinely integrated into oncology care. STELLAR aims to foster patients' long-term health and QOL by designing, implementing, and sustaining a novel telehealth treatment program for multiple risk behaviors to be integrated into standard cancer care. Telehealth delivery is evidence-based for health behavior change treatment and is well suited to overcome access and workflow barriers that can otherwise impede treatment receipt. This paper describes STELLAR's 2-arm randomized parallel group pragmatic clinical trial comparing telehealth-delivered, coach-facilitated multiple risk behavior treatment vs self-guided usual care for the outcomes of reach, effectiveness, and cost among 3000 cancer survivors who have completed curative intent treatment. This paper also discusses several challenges encountered by the STELLAR investigative team and the adaptations developed to move the research forward.

According to the World Health Organization, alcohol is a major global public health problem, leading to a significant increase in illness and death. To treat alcohol use disorders, new therapeutic tools are being promoted, among which virtual reality (VR) shows promise. Previous research has demonstrated the efficacy of VR in reducing alcohol cravings in patients, but there is a lack of data on its effectiveness in maintaining abstinence or reducing consumption in recently abstinent individuals. The E-Reva study aims to compare the efficacy of a treatment strategy combining virtual reality cue exposure therapy (VR-CET) and cognitive behavioral therapy (CBT) with conventional CBT in reducing alcohol consumption and craving in patients with alcohol use disorder (AUD). In addition to this primary objective, the study will compare the effects of VR-CET combined with CBT on anxiety, depression, rumination, and feelings of self-efficacy versus conventional CBT.

We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimer's disease and synaptic integrity. Publicly available datasets (BRAINEAC, ROSMAP, ADC1) and a cohort of asymptomatic but "at risk" individuals (PREVENT-AD) were used to explore the relationship between PTPRS and various Alzheimer's disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early Tau pathology and synaptic degeneration in Alzheimer's disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower p(181)Tau and GAP-43 levels in the CSF. In the brain, PTPRS protein abundance was significantly correlated with the quantity of two markers of synaptic integrity: SNAP25 and SYT-1. We also found the presence of sexual dimorphism for PTPRS, with higher CSF concentrations in males than females. Male carriers for variant C were found to have a 10-month delay in the onset of AD. We thus conclude that PTPRS acts as a neuroprotective receptor in Alzheimer's disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.

This study explored the decision-making experiences of patients and their partners or primary caregiver who opted for experimental active surveillance (instead of standard surgery) for the treatment of esophageal cancer.

Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation and self-harm among the caregivers of patients with cancer (CPCs).

Depression is a common cause of long-lasting disability and preoperative mental health state that has important implications for optimizing recovery in the perioperative period. In older elective surgical patients, the prevalence of preoperative depression and associated adverse pre- and postoperative outcomes are unknown. This systematic review and meta-analysis aimed to determine the prevalence of preoperative depression and the associated adverse outcomes in the older surgical population.

The extended practice of meditation may reduce the influence of state fatigue by changing neurocognitive processing. However, little is known about the preventive effects of one-session brief focused attention meditation (FAM) on state fatigue in healthy participants or its potential neural mechanisms. This study examined the preventive effects of one-session brief FAM on state fatigue and its neural correlates using resting-state functional MRI (rsfMRI) measurements.

A multitude of cellular responses to intrinsic and extrinsic signals converge on macroautophagy/autophagy, a conserved catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, particularly during starvation or stress. In addition to protein degradation, autophagy is deeply interconnected with unconventional protein secretion and polarized sorting at multiple levels within eukaryotic cells. Secretory autophagy (SA) has been recognized as a novel mechanism in which autophagosomes fuse with the plasma membrane and actively participate in the secretion of a series of cytosolic proteins, ranging from tissue remodeling factors to inflammatory molecules of the IL1 family. SA is partially controlled by the glucocorticoid-responsive, HSP90 co-chaperone FKBP5 and members of the SNARE proteins, SEC22B, SNAP23, SNAP29, STX3 and STX4. SA deregulation is implicated in several inflammatory pathologies, including cancer, cell death and degeneration. However, the key molecular mechanisms governing SA and its regulation remain elusive, as does its role in neuroinflammation and neurodegeneration. To further characterize SA and pinpoint its involvement in neuroinflammatory processes, we studied SA-relevant protein interaction networks in mouse brain, microglia and human postmortem brain tissue from control subjects and Alzheimer disease cases. We demonstrate that SA regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling.

Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate injurious fall risk (e.g., falls and fractures) compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious fall risk. We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated the time to first injurious falls within the 3-month post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Among 622,588 beneficiaries (age ≥ 65 = 84.6%, female = 58.1%, White = 82.7%; having injurious falls = 0.45%), we identified 13 distinct OPI-BZD trajectories: Group (A): Very-low OPI-only (early discontinuation) (44.9% of the cohort); (B): Low OPI-only (rapid decline) (15.1%); (C): Very-low OPI-only (late discontinuation) (7.7%); (D): Low OPI-only (gradual decline) (4.0%); (E): Moderate OPI-only (rapid decline) (2.3%); (F): Very-low BZD-only (late discontinuation) (11.5%); (G): Low BZD-only (rapid decline) (4.5%); (H): Low BZD-only (stable) (3.1%); (I): Moderate BZD-only (gradual decline) (2.1%); (J): Very-low OPI (rapid decline)/Very-low BZD (late discontinuation) (2.9%); (K): Very-low OPI (rapid decline)/Very-low BZD (increasing) (0.9%); (L): Very-low OPI (stable)/Low BZD (stable) (0.6%); and (M): Low OPI (gradual decline)/Low BZD (gradual decline) (0.6%). Compared with Group (A), six trajectories had an increased 3-month injurious falls risk: (C): HR = 1.78, 95% CI = 1.58-2.01; (D): HR = 2.24, 95% CI = 1.93-2.59; (E): HR = 2.60, 95% CI = 2.18-3.09; (H): HR = 2.02, 95% CI = 1.70-2.40; (L): HR = 2.73, 95% CI = 1.98-3.76; and (M): HR = 1.96, 95% CI = 1.32-2.91. Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing injurious fall risk of OPI-BZD use among older adults.

Perinatal mood and anxiety disorders (PMADs) affect many NICU parents and are a significant risk factor for maternal suicide. Lack of screening and treatment interferes with infant development and bonding, compounding risks in fragile infants. We aim to describe PMAD screening in level IV NICUs across the Children's Hospitals Neonatal Consortium (CHNC) and to determine the relationship between standardized screening and mental health professionals (MHPs) presence.

Although virtual care (VC) has become an integral part of oncology care and healthcare delivery, clinicians' perspectives on and satisfaction with this modality are not well understood.

Modern cancer care is costly and logistically burdensome for patients and their families despite an expansion of technology and medical advances that create the opportunity for novel approaches to care. Therefore, there is a growing appreciation for the need to leverage these innovations to make cancer care more patient centered and convenient. The Memorial Sloan Kettering Making Telehealth Delivery of Cancer Care at Home Efficient and Safe Telehealth Research Center is a National Cancer Institute-designated and funded Telehealth Research Center of Excellence poised to generate the evidence necessary to inform the appropriate use of telehealth as a strategy to improve access to cancer services that are convenient for patients. The center will evaluate telehealth as a strategy to personalize cancer care delivery to ensure that it is not only safe and effective but also convenient and efficient. In this article, we outline this new center's research strategy, as well as highlight challenges that exist in further integrating telehealth into standard oncology practice based on early experiences.

Pediatric oncology patients use totally implantable venous access devices (TIVADs) to enable central venous access. Anxiety, pain and/or discomfort are common despite anesthesia. Virtual reality (VR) is a non-pharmacological approach that may reduce pain and anxiety in these patients. We aimed to assess the use of VR for reducing anxiety/pain in patients with TIVADs while facilitating the task of healthcare providers when accessing a TIVAD.

On behalf of the Canadian Association of Psychosocial Oncology, we are pleased to present the Abstracts from the 2024 Annual Conference, titled "Building Hope: Integrating Sustainable, Innovative and Accessible Care in Psychosocial Oncology". The Conference was held in Calgary from 6 June 2024 to 7 June 2024. This conference brought together key stakeholders including multidisciplinary professionals from nursing, psychology, psychiatry, social work, spiritual care, nutrition, medicine, rehabilitation medicine, occupational health and radiation therapy for both adult and pediatric populations. Participants included clinicians, researchers, educators in cancer care, community-based organizations and patient representatives. Patients, caregivers and family members presented abstracts that speak to their role in managing cancer experiences and care. Over one hundred (150) abstracts were selected for presentation as symposia, 20 min oral presentations, 10 min oral presentations, 90 min workshops and poster presentations. We congratulate all the presenters on their research work and contribution.

The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5'-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.

To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD () were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35). For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant ( = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% ( = .076), and response rates were 39.8% and 27.2% ( = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 ( = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups. The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies. ClinicalTrials.gov identifier: NCT04688164.

Depression is associated with poor outcomes in breast cancer survivors (BCSs), with higher prevalence among younger women. The Pathways to Wellness (PTW; ClinicalTrials.gov identifier: NCT03025139) randomized controlled trial (RCT) demonstrated beneficial effects of two behavioral interventions (survivorship education [SE] and mindful awareness practices [MAPs]) on depressive symptoms in younger BCS. We conducted an exploratory secondary analysis to identify moderators of intervention effects.

Engagement in physical activity (PA) is often associated with better sleep quality and less pain severity among patients diagnosed with breast cancer. However, less research has focused on whether patients' PA prior to breast surgery, including their perceived decrease in PA level, is associated with worse preoperative sleep quality, and subsequently, greater postoperative pain. This longitudinal study investigated whether patients' preoperative PA was associated with their postoperative pain. We also explored whether preoperative sleep disturbance partially mediated the relationship between preoperative PA and postoperative pain.

Medial temporal lobe atrophy has been linked to decline in neuropsychological measures of explicit memory function. While the hippocampus has long been identified as a critical structure in learning and memory processes, less is known about contributions of the amygdala to these functions. We sought to investigate the relationship between amygdala volume and memory functioning in a clinical sample of older adults with and without cognitive impairment.

The Ras-induced ERK pathway (Raf-MEK-ERK signaling cascade) regulates a variety of cellular responses including cell proliferation, survival, and migration. Activating mutations in RAS genes, particularly in the KRAS gene, constitutively activate the ERK pathway, resulting in tumorigenesis, cancer cell invasion, and metastasis. DA-Raf1 (DA-Raf) is a splicing isoform of A-Raf and contains the Ras-binding domain but lacks the kinase domain. Consequently, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative manner and can serve as a tumor suppressor that targets mutant Ras protein-induced tumorigenesis. We show here that MEK inhibitors and DA-Raf interfere with the in vitro collective cell migration and invasion of human KRAS-mutant carcinoma cell lines, the lung adenocarcinoma A549, colorectal carcinoma HCT116, and pancreatic carcinoma MIA PaCa-2 cells. DA-Raf expression was silenced in these cancer cell lines. All these cell lines had high collective migration abilities and invasion properties in Matrigel, compared with nontumor cells. Their migration and invasion abilities were impaired by suppressing the ERK pathway with the MEK inhibitors U0126 and trametinib, an approved anticancer drug. Expression of DA-Raf in MIA PaCa-2 cells reduced the ERK activity and hindered the migration and invasion abilities. Therefore, DA-Raf may function as an invasion suppressor protein in the KRAS-mutant cancer cells by blocking the Ras-ERK pathway when DA-Raf expression is induced in invasive cancer cells.

This study describes young adult female (YA-F) cancer survivors' uncertainty management strategies related to fertility/family building. Cross-sectional data were analyzed ( = 98). Participants reported higher rates of seeking information to reduce fertility-related uncertainty (M = 5.48, ±1.03), than avoiding information (M = 4.77, ±1.29). Controlling for relevant covariates (i.e., reproductive distress, household income, and health literacy), greater avoidance was related to higher reproductive distress (β = 0.293, = 0.011) and lower household income (β = -0.281, = 0.047). Evidence suggests that some survivors may avoid fertility-related information to manage uncertainty and distress, which may impact family-building success. Fertility avoidance may be an important target of intervention.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.

There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration.

Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public health emergency. We describe the use of a simulation model of the effectiveness of COVID-19 mitigation strategies to inform a stakeholder-engaged process of rapidly designing a tailored intervention and implementation strategy for individuals with serious mental illness (SMI) and intellectual/developmental disabilities (ID/DD) in group homes in a hybrid effectiveness-implementation randomized trial.

Metabolic Syndrome (MetS) is a constellation of risk factors including abdominal obesity, high triglycerides, low HDL cholesterol (HDL-C), elevated blood pressure, and elevated fasting glucose. In Spain, according to WHO criteria, the MetS prevalence is shown to be 32% in men and 29% in women. The role of dietary habits is one of the main therapeutic strategies for the management of MetS but the most effective dietary pattern has not been established yet. This study aimed to analyze the effect of on body composition, serum lipids, and MetS components of a high-MUFA and high-fiber diet (HMFD). A case-control study was performed considering 40 cohabiting women. Participants were randomly assigned to HMFD group or high mono-unsaturated diet (HMD) group to receive one of the two proposed dietary interventions. All data (serum lipids, blood pressure, height, weight, body composition, and waist circumference) were collected fasting at baseline, 55, 98, and 132 days. The HMFD group showed higher decrease in waist circumference than in the HMD group. LDL-C dropped in both groups. Triglycerides in the HMFD group dropped during the intervention, but once the intervention was over, they returned to baseline values. The mean systolic blood pressure was lower in HMFD group. A HMFD from a weekly consumption of processed meat (Torrezno de Soria) deeply fried in extra virgin olive oil in combination with vegetables logged in a Mediterranean diet can improve MetS risk factors in healthy overweight women.

The key pathological signature of ALS/ FTLD is the mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm. However, TDP-43 gain of function in the cytoplasm is still poorly understood since TDP-43 animal models recapitulating mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm are missing.

Nonfatal suicidality is the most robust predictor of suicide death. However, only ~10% of those who survive an attempt go on to die by suicide. Moreover, ~50% of suicide deaths occur in the absence of prior known attempts, suggesting risks other than nonfatal suicide attempt need to be identified. We studied data from 4,000 population-ascertained suicide deaths and 26,191 population controls to improve understanding of risks leading to suicide death. This study included 2,253 suicide deaths and 3,375 controls with evidence of nonfatal suicidality (SUI_SI/SB and CTL_SI/SB) from diagnostic codes and natural language processing of electronic health records notes. Characteristics of these groups were compared to 1,669 suicides with no prior nonfatal SI/SB (SUI_None) and 22,816 controls with no lifetime suicidality (CTL_None). The SUI_None and CTL_None groups had fewer diagnoses and were older than SUI_SI/SB and CTL_SI/SB. Mental health diagnoses were far less common in both the SUI_None and CTL_None groups; mental health problems were less associated with suicide death than with presence of SI/SB. Physical health diagnoses were conversely more often associated with risk of suicide death than with presence of SI/SB. Pending replication, results indicate highly significant clinical differences among suicide deaths with versus without prior nonfatal SI/SB.

To investigate gender-specific factors associated with case complexity in a population-based sample of middle-aged and older adults using a holistic approach to complexity.

Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. However, the heterogenicity and plasticity of liver cells have made it controversial. Here, by employing single-cell RNA-sequencing technology, transcriptome features of Krt19 bile duct lineage cells isolated from Krt19CreERT; Rosa26R-GFP reporter mouse livers are examined. Distinct biliary epithelial cells which include adult LSCs, as well as their downstream hepatocytes and cholangiocytes are identified. Importantly, a novel cell surface LSCs marker, CD63, as well as CD56, which distinguished active and quiescent LSCs are discovered. Cell expansion and bi-potential differentiation in culture demonstrate the stemness ability of CD63 cells in vitro. Transplantation and lineage tracing of CD63 cells confirm their contribution to liver cell mass in vivo upon injury. Moreover, CD63CD56 cells are proved to be activated LSCs with vigorous proliferation ability. Further studies confirm that CD63CD56 quiescent LSCs express VEGFR2 and FGFR1, and they can be activated to proliferation and differentiation through combination of growth factors: VEGF-A and bFGF. These findings define an authentic adult liver stem cells compartment, make a further understanding of fate regulation on LSCs, and highlight its contribution to liver during pathophysiologic processes.

Nanocomposites are sophisticated materials that incorporate nanostructures into matrix materials, such as polymers, ceramics and metals. Generally, the marine ecosystem exhibits severe variability in terms of light, temperature, pressure, and nutrient status, forcing the marine organisms to develop variable, complex and unique chemical structures to boost their competitiveness and chances of survival. Polymers sourced from marine creatures, such as chitin, chitosan, alginate, sugars, proteins, and collagen play a crucial role in the bioengineering field, contributing significantly to the development of nanostructures like nanoparticles, nanocomposites, nanotubes, quantum dots, etc. These nanostructures offer a wide array of features involving mechanical strength, thermal stability, electrical conductivity, barrier and optical characteristics compared to traditional composites. Notably, marine nanocomposites have distinctive roles in a wide spectrum of applications, among them anti-cancer, anti-microbial, antioxidant, cytotoxic, food packing, tissue engineering and catalytic actions. Sol-gel, hot pressing, chemical vapor deposition, catalytic decomposition, dispersion, melt intercalation, in situ intercalative polymerization, high-energy ball milling and template synthesis are common processes utilized in engineering nanocomposites. According to our literature survey and the Web of Science, chitosan, followed by cellulose, chitin and MAPs emerge as the most significant marine polymers utilized in the construction of nanocomposites. Taken together, the current manuscript underscores the biogenesis of nanocomposites, employing marine polymers using eco-friendly processes. Furthermore, significant emphasis in this area is needed to fully explore their capabilities and potential benefits. To the best of our knowledge, this manuscript stands as the first comprehensive review that discusses the role of marine-derived polymers in engineering nanocomposites for various applications.

It is unclear whether cannabis use is associated with adverse health outcomes in patients with COVID-19 when accounting for known risk factors, including tobacco use.

The COVID-19 pandemic has highlighted the critical importance of robust healthcare capacity planning and preparedness for emerging crises. However, healthcare systems must also adapt to more gradual temporal changes in disease prevalence and demographic composition over time. To support proactive healthcare planning, statistical capacity forecasting models can provide valuable information to healthcare planners. This systematic literature review and evidence mapping aims to identify and describe studies that have used statistical forecasting models to estimate healthcare capacity needs within hospital settings.

The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing (CoPEC).

Administration mode of patient-reported outcome measures (PROMs) may influence responses. We assessed if Patient Health Questionnaire-9 (PHQ-9), Edinburgh Postnatal Depression Scale (EPDS) and Hospital Anxiety and Depression Scale - Depression subscale (HADS-D) item responses and scores were associated with administration mode. We compared (1) self-administration versus interview-administration; within self-administration (2) research or medical setting versus private; and (3) pen-and-paper versus electronic; and within interview-administration (4) in-person versus phone. We analysed individual participant data meta-analysis datasets with item-level data for the PHQ-9 (N = 34,529), EPDS (N = 16,813), and HADS-D (N = 16,768). We used multiple indicator multiple cause models to assess differential item functioning (DIF) by administration mode. We found statistically significant DIF for most items on all measures due to large samples, but influence on total scores was negligible. In 10 comparisons conducted across the PHQ-9, EPDS, and HADS-D, Pearson's correlations and intraclass correlation coefficients between latent depression symptom scores from models that did or did not account for DIF were between 0.995 and 1.000. Total PHQ-9, EPDS, and HADS-D scores did not differ materially across administration modes. Researcher and clinicians who evaluate depression symptoms with these questionnaires can select administration methods based on patient preferences, feasibility, or cost.

Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data.

Generation Scotland (GS) is a large family-based cohort study established as a longitudinal resource for research into the genetic, lifestyle and environmental determinants of physical and mental health. It comprises extensive genetic, sociodemographic and clinical data from volunteers in Scotland.

Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions.

Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.

People with systemic sclerosis (SSc) face barriers to physical activity. Few studies have described physical activity in SSc, and none have explored physical activity longitudinally during COVID-19. We evaluated physical activity from April 2020 to March 2022 among people with SSc.

The geriatric failure to thrive, a controversial French concept not present in the international literature, was first characterized by Jean Carrié in 1956. It is described as a process of aging and physical and psychological decline associated with advanced age, manifesting as a pronounced overall deterioration. In this case report, we present the case of an 88-year-old patient, admitted to a general medicine service for geriatric failure to thrive, whose management eventually leads to the diagnosis of endocarditis with digestive cancer complicated by a characterized depressive episode. This case prompts us to consider the geriatric failure to thrive with extreme caution and challenges the legitimacy of such a diagnosis in the context of an aging population and the progress of medical sciences.

Pathogenic variants in GFPT1, encoding a key enzyme to synthesize UDP-N-acetylglucosamine (UDP-GlcNAc), cause congenital myasthenic syndrome (CMS). We made a knock-in (KI) mouse model carrying a frameshift variant in Gfpt1 exon 9 simulating a CMS patient. As Gfpt1 exon 9 is exclusively included in striated muscles, Gfpt1-KI mice were deficient for Gfpt1 only in skeletal muscles. In Gfpt1-KI mice, (i) UDP-HexNAc, CMP-NeuAc, and protein O-GlcNAcylations were reduced in skeletal muscles; (ii) aged Gfpt1-KI mice showed poor exercise performance and abnormal neuromuscular junction structures; and (iii) markers for unfolded protein response (UPR) were elevated in skeletal muscles. Denervation-mediated enhancement of ER stress in Gfpt1-KI mice facilitated protein folding, ubiquitin-proteasome degradation, and apoptosis, whereas autophagy was not induced and protein aggregates were markedly increased. Lack of autophagy was accounted for by enhanced degradation of FoxO1 by increased Xbp1-s/u proteins. Similarly, in Gfpt1-silenced C2C12 myotubes, ER stress exacerbated protein aggregates and activated apoptosis, but autophagy was attenuated. In both skeletal muscles in Gfpt1-KI mice and Gfpt1-silenced C2C12 myotubes, maladaptive UPR failed to eliminate protein aggregates and provoked apoptosis.

A pilot randomized controlled trial was conducted to examine the effectiveness of a storybook package for enhancing the perceived knowledge and confidence of health and social care professionals in working with bereaved child siblings and their parents before and after the loss. Open-ended questions were asked to collect feedback, and thematic analyses were conducted to generate the themes. Quantitative findings provided preliminary but not strong evidence of its effectiveness, but qualitative findings showed that participants perceived their knowledge about supporting bereaved siblings and their parents was enhanced and considered the storybook package a useful tool for facilitating their practice. Participants also reflected on how real and specific the stories in the storybook should be. This study is the first step in developing an evidence-based practice tool for health and social care professionals. Future studies are required to further examine its effectiveness for practice.

The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease.

Studies have reported that the rapid rise in heated tobacco product (HTP) sales in Japan accompanied an accelerated decline in cigarette sales. However, these studies do not distinguish whether those who previously smoked cigarettes became dual users with HTPs (smoking fewer cigarettes) or instead switched completely to HTPs. If HTPs present lower health risks than cigarettes, replacing cigarettes with HTPs is more likely to improve public health than cigarette users continuing as dual users.

This Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV. Along with this guidance, the Report reviews what is known about the origin of the heartbeat and its neural control, including factors that produce and influence HRV metrics. The Report concludes with checklists to guide authors in study design and analysis considerations, as well as guidance on the reporting of key methodological details and characteristics of the samples under study. It is expected that rigorous and transparent recording and reporting of HR and HRV measures will strengthen inferences across the many applications of these metrics in psychophysiology. The prior Committee Reports on HR and HRV are several decades old. Since their appearance, technologies for human cardiac and vascular monitoring in laboratory and daily life (i.e., ambulatory) contexts have greatly expanded. This Committee Report was prepared for the Society for Psychophysiological Research to provide updated methodological and interpretive guidance, as well as to summarize best practices for reporting HR and HRV studies in humans.

Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported.

Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics.

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Describe the screening, referral, and treatment delivery associated with an opt-out tobacco treatment program (TTP) implemented in six hospitals varying in size, rurality and patient populations.

Extracellular vesicles such as exosomes are now recognized as key players in intercellular communication. Their role is influenced by the specific repertoires of proteins and lipids, which are enriched when they are generated as intraluminal vesicles (ILVs) in multivesicular endosomes. Here we report that a key component of small extracellular vesicles, the tetraspanin CD63, sorts cholesterol to ILVs, generating a pool that can be mobilized by the NPC1/2 complex, and exported via exosomes to recipient cells. In the absence of CD63, cholesterol is retrieved from the endosomes by actin-dependent vesicular transport, placing CD63 and cholesterol at the centre of a balance between inward and outward budding of endomembranes. These results establish CD63 as a lipid-sorting mechanism within endosomes, and show that ILVs and exosomes are alternative providers of cholesterol.

Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC.

The glymphatic system is cerebrospinal fluid-brain tissue fluid exchange flow mediated by aquaporin-4 (AQP4) on the end feet of astrocytes for a system, which is capable of rapidly removing brain metabolites and thus maintaining brain homeostasis, and is known as the central immune system. Dysfunction of the glymphatic system causes accumulation of misfolded and highly phosphorylated proteins (amyloid-β and Tau proteins), which destabilizes the proteins, and the body's neuroinflammatory factors are altered causing aging of the immune system and leading to neurodegenerative diseases. Damage to the glymphatic system and aging share common manifestations, as well as unstudied biological mechanisms that are also linked, such as mitochondria, oxidative stress, chronic inflammation, and sleep. In this paper, we first summarize the structure, function, and research methods of the glymphatic system and the relationship between the glymphatic system and the peripheral immune system, and second, sort out and summarize the factors of the glymphatic system in removing metabolites and resolving aging-related diseases and factors affecting aging, to explore its related biological mechanisms, and moreover, to provide a new way of thinking for treating or intervening aging-related diseases.

Patients receiving palliative care often face psychological distress, which can be challenging for clinicians to manage. Therefore, reflexive and visual journaling can be used as powerful techniques for clinician selfreflection and personal development. These journals are a form of practice wisdom, providing insights into psychological health in palliative care.

Mental health for cancer survivors in both research and clinical applications has strongly adopted a traditional nosological approach, involving the classification of psychopathology into discrete disorders. However, this approach has recently faced considerable criticism due to issues such as high comorbidity and within-disorder symptom heterogeneity across populations. Moreover, there are additional specific issues impacting the validity of traditional approaches in cancer survivorship populations, including the physiological effects of cancer and its treatments. In response, we provide the case for the hierarchical dimensional approach within psycho-oncology, in particular the Hierarchical Taxonomy of Psychopathology (HiTOP). We discuss not only the potential utility of HiTOP to research and clinical applications within psycho-oncology, but also its limitations, and what is required to apply this approach within cancer survivorship.

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.

Polysubstance use is associated with adverse health outcomes, yet little research has measured changes in polysubstance use. We aimed to 1) estimate trends in marijuana and heavy alcohol use by cigarette smoking and demographic subgroups, and 2) examine patient factors associated with concurrent use among adults who were smoking.

Tapentadol is a drug of choice for neuropathic cancer pain. questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members towards one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but non-financial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analysing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated towards COVID-19 elimination (zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases towards advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Depression is prevalent among individuals who smoke cigarettes and increases risk for relapse. A previous clinical trial suggests that Goal2Quit, a behavioral activation-based smoking cessation mobile app, effectively increases smoking abstinence and reduces depressive symptoms. Secondary analyses were conducted on these trial data to identify predictors of success in depression-specific digitalized cessation interventions. Adult who smoked cigarettes (age = 38.4 ± 10.3, 53% women) were randomized to either use Goal2Quit for 12 weeks ( = 103), paired with a 2-week sample of nicotine replacement therapy (patch and lozenge) or to a Treatment-As-Usual (TAU) control ( = 47). The least absolute shrinkage and selection operator was utilized to identify a subset of baseline variables predicting either smoking or depression intervention outcomes. The retained predictors were then fitted linear regression models to determine relations to each intervention outcome. Relative to TAU, only individuals who spent significant time using Goal2Quit (56 ± 46 min) were more likely to reduce cigarette use by at least 50% after 12 weeks, whereas those who spent minimal time using Goal2Quit (10 ± 2 min) did not exhibit significant changes. An interaction between educational attainment and treatment group revealed that, as compared to TAU, only app users with an educational degree beyond high school exhibited significant reductions in depression. The findings highlight the importance of tailoring depression-specific digital cessation interventions to individuals' unique engagement needs and educational level. This study provides a potential methodological template for future research aimed at personalizing technology-based treatments for cigarette users with depressive symptoms.

Communicating effectively with patients having a traditional, alternative or complementary medicine-related health-belief model is challenging in today's cross-cultural society. This narrative review explores the integrative medicine setting of care, focusing on insights from the integrative oncology daily practice, while addressing the relevance to the mental health setting. The way in which healthcare providers can enhance cultural-sensitive communication with patients and informal caregivers; recognize and respect health-beliefs to bridge cultural gaps; and generate an open, non-judgmental and mindful dialogue are discussed.

Confronting a breast cancer diagnosis, along with complex and challenging treatment procedures, is an extremely stressful experience. Psychological resilience is the ability to maintain or restore normal functioning while facing adversity. We aimed to explore the impact of an early breast cancer diagnosis on psychological resilience, distress, and perception of health. A cross-sectional study was conducted, including 50 patients newly diagnosed with early breast cancer and 67 healthy women with screening mammograms graded 1 or 2 using a Breast Imaging Reporting and Data System. The levels of distress, perception of health, and psychological resilience were assessed using the depression, anxiety, and stress scale, the SF 36-Item Health Survey 1.0, and the Connor-Davidson RISC-25 scale. Differences between variables were examined using the -test and chi-square test for interval and categorial variables. The surveys were conducted within four weeks of a breast cancer diagnosis. Patients with breast cancer reported a deterioration of their health relative to the previous year and significantly higher levels of psychological resilience, while there was no significant difference between the groups in levels of stress, anxiety, or depression. The process of diagnosis with early breast cancer may activate psychological dynamic processes which are involved in the effective adaptation to acute stress, leading to higher resilience levels in breast cancer patients compared to healthy controls.

The coronavirus disease 2019 (COVID-19) pandemic outbreak created a challenge to manage the health, especially the mental health of various care providers involved in treating the patients infected with the virus. Previously published literature has shown a significant effect of the pandemic on the psychological health of healthcare workers (HCWs) globally; so, this study aimed to describe the psychological health outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Indian HCWs.

Human papillomavirus (HPV) vaccinations are lower than expected. To protect the onset of head and neck cancers, innovative strategies to improve the rates are needed. Artificial intelligence may offer some solutions, specifically conversational agents to perform counseling methods. We present our efforts in developing a dialogue model for automating motivational interviewing (MI) to encourage HPV vaccination. We developed a formalized dialogue model for MI using an existing ontology-based framework to manifest a computable representation using OWL2. New utterance classifications were identified along with the ontology that encodes the dialogue model. Our work is available on GitHub under the GPL v.3. We discuss how an ontology-based model of MI can help standardize/formalize MI counseling for HPV vaccine uptake. Our future steps will involve assessing MI fidelity of the ontology model, operationalization, and testing the dialogue model in a simulation with live participants.

Manganese (Mn) is an essential heavy metal in the human body, while excess leads to neurotoxicity, as observed in this study, where 100 µM of was administered to the human neuroblastoma (SH-SY5Y) cell model of dopaminergic neurons in neurodegenerative diseases. We quantitated pathway and gene changes in homeostatic cell-based adaptations to exposure. Utilizing the Gene Expression Omnibus, we accessed the GSE70845 dataset as a microarray of SH-SY5Y cells published by Gandhi et al. (2018) and applied statistical significance cutoffs at < 0.05. We report 74 pathway and 10 gene changes with statistical significance. ReactomeGSA analyses demonstrated upregulation of histones (5 out of 10 induced genes) and histone deacetylases as a neuroprotective response to remodel/mitigate -induced DNA/chromatin damage. Neurodegenerative-associated pathway changes occurred. NF-κB signaled protective responses via Sirtuin-1 to reduce neuroinflammation. Critically, activated three pathways implicating deficits in purine metabolism. Therefore, we validated that urate, a purine and antioxidant, mitigated -losses of viability in SH-SY5Y cells. We discuss as a hypoxia mimetic and trans-activator of HIF-1α, the central trans-activator of vascular hypoxic mitochondrial dysfunction. induced a 3-fold increase in mRNA levels for antioxidant metallothionein-III, which was induced 100-fold by hypoxia mimetics deferoxamine and zinc.

Hydrogen peroxide (HO) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more HO during abnormal tumor growth. There has been a considerable amount of interest in utilizing HO as a biomarker for the diagnosis of cancer tissue. In this study, an electrochemical sensor for HO was constructed based on 3D reduced graphene oxide (rGO), MXene (TiC), and multi-walled carbon nanotubes (MWCNTs) composite. Three-dimensional (3D) rGO-TiC-MWCNTs sensor showed good linearity for HO in the ranges of 1-60 μM and 60 μM-9.77 mM at a working potential of -0.25 V, with sensitivities of 235.2 µA mM cm and 103.8 µA mM cm, respectively, and a detection limit of 0.3 µM (S/N = 3). The sensor exhibited long-term stability, good repeatability, and outstanding immunity to interference. In addition, the modified electrode was employed to detect real-time HO release from cancer cells and cancer tissue ex vivo.

The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer.

Oral squamous cell carcinoma (OSCC) has numerous physical, psychosocial and financial implications, which significantly affect patients' quality of life. We aimed to determine the health-related quality of life (HRQoL) and identify quality of life (QoL) predictors in patients with OSCC.

Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5-4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance.

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

Alzheimer's disease (AD) is one of the most common chronic neurodegenerative diseases. Hyperphosphorylated tau plays an indispensable role in neuronal dysfunction and synaptic damage in AD. Proteolysis-targeting chimeras (PROTACs) are a novel type of chimeric molecule that can degrade target proteins by inducing their polyubiquitination. This approach has shown promise for reducing tau protein levels, which is a potential therapeutic target for AD. Compared with traditional drug therapies, the use of PROTACs to reduce tau levels may offer a more specific and efficient strategy for treating AD, with fewer side effects. In the present study, we designed and synthesized a series of small-molecule PROTACs to knock down tau protein. Of these, compound was able to lower both total and phosphorylated tau levels in HEK293 cells with stable expression of wild-type full-length human tau (termed HEK293-htau) and htau-overexpressed mice. Western blot findings indicated that degraded tau protein through the ubiquitin-proteasome system in a time-dependent manner. In htau-overexpressed mice, the results of both the novel object recognition and Morris water maze tests revealed that markedly improved cognitive function. Together, our findings suggest that the use of the small-molecule PROTAC to degrade phosphorylated tau may be a promising therapeutic strategy for AD.

Social media data provide unprecedented access to discussions of active, naturalistic, and often real-time cannabis use in an era of cannabis policy liberalization. The aim of this study was to explore psychological and environmental correlates of cannabis effects by applying computational social science approaches to a large dataset of unprompted reports of naturalistic cannabis use with corresponding self-reported numerical ratings of subjective highness. Post title text was extracted via the Pushshift dataset from N = 328,865 posts to the r/trees Reddit community, where posters self-assess and disclose how high they feel on a scale from 1 to 10 (M = 6.9, SD = 1.8). Structural topic modelling and Linguistic Inquiry and Word Count (LIWC) dictionary-based approaches were applied to identify (1) frequently discussed topics and (2) text indicative of 5 psychological processes (affective, social, cognitive, perceptual, biological), respectively, as well as to examine relationships between subjective highness and (1) topic prevalence and (2) psychological process word counts. A 40-topic model was selected for interpretation based on semantic coherence and exclusivity. The most discussed topics in a 40-topic model were characterized by references to smoking places, social contexts, positive affect, cognitive states, as well as food and media consumed. In LIWC dictionary analyses, words mentioning affective, social, and cognitive processes were referenced more often than perceptual or body processes. Posters reported greater subjective highness when using language that referred to in-person social environments and lower subjective highness when using language that referred to online social environments and positive affect psychological states. This examination of unprompted online reports of naturalistic cannabis use identified textual content referring to affect and to other people as being associated with perceived effects of cannabis. These affective and social aspects of the cannabis use experience were salient to active posters in this online community and should be integrated into experience sampling methods and behavioral pharmacology research, as well as public health messaging.

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited allele is epigenetically silenced in neurons during development by a noncoding transcript (). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function-either by gene addition or by targeting -are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and hybridization, we mapped UBE3A and regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal silencing in neurons-but not glial cells-in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of linked to AS.

The e-cigarette market is large and diverse. Traditional smoking cessation trials involving a control group and a 6-month observation period are an inefficient methodology for testing the multiple treatment options e-cigarettes provide for harm reduction in cigarette smokers. We determined when product substitution occurred in the e-cigarette provision arm of an e-cigarette substitution trial for cigarette smokers who were not interested in quitting.

Pooled designs for single-cell RNA sequencing, where many cells from distinct samples are processed jointly, offer increased throughput and reduced batch variation. This study describes expression-aware demultiplexing (EAD), a computational method that employs differential co-expression patterns between individuals to demultiplex pooled samples without any extra experimental steps.

While voltage-gated potassium channels have critical roles in controlling neuronal excitability, they also have non-ion-conducting functions. Kv8.1, encoded by the KCNV1 gene, is a 'silent' ion channel subunit whose biological role is complex since Kv8.1 subunits do not form functional homotetramers but assemble with Kv2 to modify its ion channel properties. We profiled changes in ion channel expression in amyotrophic lateral sclerosis patient-derived motor neurons carrying a superoxide dismutase 1(A4V) mutation to identify what drives their hyperexcitability. A major change identified was a substantial reduction of KCNV1/Kv8.1 expression, which was also observed in patient-derived neurons with C9orf72 expansion. We then studied the effect of reducing KCNV1/Kv8.1 expression in healthy motor neurons and found it did not change neuronal firing but increased vulnerability to cell death. A transcriptomic analysis revealed dysregulated metabolism and lipid/protein transport pathways in KCNV1/Kv8.1-deficient motor neurons. The increased neuronal vulnerability produced by the loss of KCNV1/Kv8.1 was rescued by knocking down Kv2.2, suggesting a potential Kv2.2-dependent downstream mechanism in cell death. Our study reveals, therefore, unsuspected and distinct roles of Kv8.1 and Kv2.2 in amyotrophic lateral sclerosis-related neurodegeneration.

Despite high survival rates for many adolescent or young adult (AYA) cancer diagnoses, the psychosocial, academic, and vocational repercussions for survivors are profound and enduring. Hospital systems are able to address many AYA needs, but the ability to provide the human connectedness and knowledge that drive long-term school and career planning is lacking. This study assessed a group of AYAs who have or had cancer (n = 108, 54% female, 71% white, mean age 20.6 ± 4.4) to determine the school, career, medical, emotional, and psychosocial needs that are not currently being met by hospital staff and support networks. We identified the most common unmet needs of AYAs, differences between needs of AYAs in active treatment and survivorship, and the role of a career-focused mentoring program developed by the nonprofit organization Connecting Champions (CC) to address the array of unmet AYA needs. We found that the most commonly reported needs were all related to career and school, and that the top needs did not differ significantly throughout the cancer journey. These findings suggest that career and school-based needs are a high priority for AYAs, yet social isolation can make the necessary people or resources inaccessible. The CC mentoring program was reported as effective in attending to unmet needs (with an average score of 95.1/100) and can be a valuable resource for hospital systems, nonprofit organizations, and health insurers to provide personalized, career-focused support to AYAs during cancer treatment and survivorship.

In the past 40 years, the gradually increasing incidence and mortality rates of malignant tumors have severely impacted the quality of life of patients, bringing significant physical and psychological burdens and becoming an increasingly serious social issue. With the development of medical standards, new methods for cancer detection and treatment have been continuously proposed. Although it has been proven that cancer is related to increased psychological burden and suicidal behaviors in patients, current research on the psychological burden caused by cancer is insufficient. Clinicians often overlook the psychological health issues of patients while treating their physical diseases. Considering the high incidence of cancer, this review will outline the psychological burdens of cancer patients worldwide in recent years and its high-risk factors. Moreover, this review will summarize the common methods for evaluating psychological burdens, present current predictive models and treatment methods for the psychological burden of cancer patients, aiming to provide a research basis and future direction for the timely and accurate assessment of the psychological burden in cancer patients.

Rapid diagnostic clinics (RDCs) provide a streamlined holistic pathway for patients presenting with non-site specific (NSS) symptoms concerning of malignancy. The current study aimed to: 1) assess the prevalence of anxiety and depression, and 2) identify a combination of patient characteristics and symptoms associated with severe anxiety and depression at Guy's and St Thomas' Foundation Trust (GSTT) RDC in Southeast London. Additionally, we compared standard statistical methods with machine learning algorithms for predicting severe anxiety and depression.

Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids.

Poor sleep quality impedes the progression of chronic illnesses, while chronic illnesses themselves are caused by poor sleep quality. Despite this fact, there is no research that has been conducted in Ethiopia that provides a thorough estimate of the self-reported sleep quality among patients with chronic illnesses. In order to present a complete picture of poor sleep quality among diabetes, hypertension, heart failure, cancer, HIV/AIDS and epilepsy patients, this systematic review and meta-analysis was carried out.