Cancer and Psychiatry

Bipolar disorder is a mood illness that affects many people. It has a high recurrence frequency and will cause significant damage to the patient's social function. At present, the pathogenesis of BD is not clear. The National Center for Biotechnology Information (NCBI) established and maintained the Gene Expression Omnibus (GEO) database, a gene expression database. For bioinformatics analysis, researchers can obtain expression data from the internet. At present, the samples of the dataset used in the research of BD are mostly from brain tissue, and the data containing blood samples are rarely used. GEO databases (GSE46416, GSE5388, and GSE5389) were used to retrieve public data, and utilizing the online tool GEO2R, differentially expressed genes (DEGs) were retrieved. The common DEGs between the samples of patients with BD and the samples of the normal population were screened by Venn diagrams. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional annotation and pathway enrichment analysis of DEGs. A protein-protein interaction network (PPI) was built to investigate hub genes on this basis. There were 117 up-regulated DEGs and 38 down-regulated DEGs discovered, with two hub genes [SRC, CDKN1A] among the up-regulated DEGs. These two hub genes were also highly enriched in the oxytocin signaling pathway, proteoglycans in cancer and bladder cancer, according to KEGG analysis. The results of the receiver operating characteristic curve (ROC) of SRC and CDKN1A in the three datasets strongly suggested that SRC and CDKN1A were potential diagnostic markers of BD. The results strongly suggest that SRC and CDKN1A are related to the pathogenesis of BD.

Solid organ transplant recipients experience a period of unique vulnerability during adolescence, when normative developmental changes intersect with health-related variables to influence psychological health.

Lung cancer is the leading cause of cancer death among American Indian and Alaska Native (AI/AN) people, and AI/AN people have the highest rate of smoking of any racial or ethnic group in the US. There is limited research to inform culturally-relevant strategies for lung cancer prevention inclusive of lung cancer screening (LCS). The objective of this study was to understand determinants of LCS and tobacco cessation care in at-risk urban-dwelling AI/ANs.

This study aimed to characterize unmet reproductive health needs of female young adult survivors of childhood cancer (YASCC), as understood by oncology providers ( = 10) caring for this patient population. Providers completed brief online questionnaires and a one-time semi-structured interview. Descriptive statistics characterized quantitative data, and rapid qualitative analysis identified themes in interview data. In survey data, providers rated fertility as a top concern among YASCC. Qualitative data identified specific under-addressed reproductive sexual health information needs for patients and also for their providers. The results provide preliminary knowledge to inform the development of behavioral interventions to address patients' unmet needs.

The diagnosis of a primary brain tumor (PBT) causes significant distress for the caregiver-patient dyad, warranting increased supportive care intervention. Although researchers have previously assessed caregivers' perceptions of their own supportive care needs, no study to date has identified how patients perceive the caregiving experience and/or patients' recommendations for integrating supportive care of caregivers in neuro-oncology. This qualitative study examined caregiver distress as well as caregiver supportive care needs from the patients' perspective to inform future intervention development.

The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs.

There are significant rural/urban disparities that exist in cancer and chronic disease morbidity and mortality, many of which are attributed to increased tobacco use prevalence in rural populations compared to urban. Understanding differences in rural and urban tobacco use patterns is key to developing targeted interventions.

Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare.

Oligodendrocytes, the myelin-producing cells in the central nervous system (CNS), are crucial for rapid action potential conduction and neuronal communication. While extensively studied for their roles in neuronal support and axonal insulation, their involvement in pain modulation is an emerging research area. This review explores the interplay between oligodendrocytes, myelination, and pain, focusing on neuropathic pain following peripheral nerve injury, spinal cord injury (SCI), chemotherapy, and HIV infection. Studies indicate that a decrease in oligodendrocytes and increased cytokine production by oligodendroglia in response to injury can induce or exacerbate pain. An increase in endogenous oligodendrocyte precursor cells (OPCs) may be a compensatory response to repair damaged oligodendrocytes. Exogenous OPC transplantation shows promise in alleviating SCI-induced neuropathic pain and enhancing remyelination. Additionally, oligodendrocyte apoptosis in brain regions such as the medial prefrontal cortex is linked to opioid-induced hyperalgesia, highlighting their role in central pain mechanisms. Chemotherapeutic agents disrupt oligodendrocyte differentiation, leading to persistent pain, while HIV-associated neuropathy involves up-regulation of oligodendrocyte lineage cell markers. These findings underscore the multifaceted roles of oligodendrocytes in pain pathways, suggesting that targeting myelination processes could offer new therapeutic strategies for chronic pain management. Further research should elucidate the underlying molecular mechanisms to develop effective pain treatments.

This study examined the relationship between multidimensional patient concerns and anxiety and depression in a national sample of older adults with cancer (OACs ≥ 65 years) and the buffering effect of visiting providers across disciplines (e.g., oncology, allied health, primary care, mental health) on these relationships.

Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of quercetin. Methods: The developed Alg@Qc@ZIF-8 was characterized using SEM, DLS, FTIR, TGA, BET, and XRD. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. Results: SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, -23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02 %. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more quercetin at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 hours. Furthermore, the IC50 value of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net quercetin. Conclusions: Considering the in vitro and in vivo outcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management. .

To test whether the association between flavor at first vape and continued use is mediated through subjective experience at first vape.

Audiovestibular dysfunction in patients with systemic lupus erythematosus has been underestimated for decades. Systemic lupus erythematosus can affect both the auditory and vestibular systems simultaneously. Several potential pathophysiological mechanisms behind systemic lupus erythematosus-related audiovestibular dysfunction have been proposed, including antibody-mediated immune responses, cell-mediated cytotoxicity, immune complex deposition in microvessels, central involvement in the audiovestibular pathway, and ototoxicity from medications used in systemic lupus erythematosus treatment. Currently available tests to evaluate audiovestibular function in systemic lupus erythematosus patients are neither specific nor sensitive. Nevertheless, there is no consensus regarding the efficacy of treatments for audiovestibular dysfunction in such patients. In this systematic review, we electronically searched the PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect platforms to find eligible articles. The first inspection date was on 29 December 2023 and the final update search date was on 11 June 2024. Further, we rated the quality of the included articles with Newcastle-Ottawa Scale. Based upon the aforementioned systematic review process, we have summarized the currently available evidence on the characteristics, pathophysiology, examination, and treatment of audiovestibular dysfunction related to systemic lupus erythematosus. Furthermore, we have proposed a specific steroid treatment protocol to manage audiovestibular dysfunction related to systemic lupus erythematosus. Audiovestibular dysfunction related to systemic lupus erythematosus may be responsive to adequate treatments, potentially allowing for reversibility if the disease is recognized and managed in a timely manner. Therefore, to provide clinically relevant evidence to clinicians, we have organized this literature review article to summarize the available evidence on the characteristics, pathophysiology, examination, and treatment of audiovestibular dysfunction in patients with systemic lupus erythematosus. Finally, based on our modified steroid treatment protocol, we would like to provide a new treatment strategy to clinicians to manage systemic lupus erythematosus-related audiovestibular dysfunction.

Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by bi-allelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome (RTPS1). With increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable. This study focuses on exploring SMARCB1 germline alterations, notably mosaicism in blood samples of children with RT and in parents, using a custom NGS panel.

Cyclin-dependent kinase 8 (CDK8) is highly expressed in various cancers and common complex human diseases, and an important therapeutic target for drug discovery and development. The CDK8 inhibitors are actively sought after, especially among natural products. We performed a virtual screening using the ZINC library comprising approximately 90,000 natural compounds. We applied Lipinski's rule of five, absorption, distribution, metabolism, excretion, and toxicity properties, and pan-assay interference compounds filter to eliminate promiscuous binders. Subsequently, the filtered compounds underwent molecular docking to predict their binding affinity and interactions with the CDK8 protein. Interaction analysis were carried out to elucidate the interaction mechanism of the screened hits with binding pockets of the CDK8. The ZINC02152165, ZINC04236005, and ZINC02134595 were selected with appreciable specificity and affinity with CDK8. An all-atom molecular dynamic (MD) simulation followed by essential dynamics was performed for 200 ns. Taken together, the results suggest that ZINC02152165, ZINC04236005, and ZINC02134595 can be harnessed as potential leads in therapeutic development. Moreover, the binding of the molecules brings change in protein conformation in a way that blocks the ATP-binding site of the protein, obstructing its kinase activity. These new findings from natural products offer insights into the molecular mechanisms underlying CDK8 inhibition. CDK8 was previously associated with behavioral and neurological diseases such as autism spectrum disorder, and cancers, for example, colorectal, prostate, breast, and acute myeloid leukemia. Hence, we call for further research and experimental validation, and with an eye to inform future clinical drug discovery and development in these therapeutic fields.

Delirium is common among older hospitalized adults. In addition to presenting immediate management issues, delirium can increase the long-term risk of dementia, institutionalization, and mortality. Delirium is associated with disrupted sleep, and prior studies suggest that some specific sleep-promoting agents may reduce delirium.

Many individuals change their smoking habits after cancer diagnosis. We aimed to evaluate the association of post-diagnosis smoking habit change with incident dementia in cancer survivors.

The accumulation of β-amyloid oligomers is a hallmark of Alzheimer's disease, inducing neural and network dysfunction in the early stages of pathology. The hippocampus is affected early in the pathogenesis of AD, however the impact of soluble β-amyloid on the dentate gyrus (DG) subregion of the hippocampus and its interaction with nicotinic acetylcholine receptors (nAChRs) within this region are not known. Using a localized model of over-expression, we show that β-amyloid induces early-onset neuronal hyperactivity and hippocampal-dependent memory deficits in mice. Further, we find the DG region to be under potent and sub-type specific nicotinic control in both healthy and pathophysiological conditions, with targeted receptor inhibition leading to a mnemonic rescue against localized amyloidosis. We show that while neurogenesis and synaptic functions are not severely affected in our model, reducing β2-containing nAChR function is associated with the promotion of young adult-born neurons within the pathological network, suggesting a possible protective mechanism. Our data thus reveal the DG network level changes which occur in the early-stages of β-amyloid accumulation and highlight the downstream consequences of targeted nicotinic neuromodulation.

Tele-assisted home-based palliative care (THPC) usually fulfills the desire of terminal patients to pass away at home. The overall costs of such a service deserve evaluation. This study aims to determine health care utilization and costs for cancer patients at the end of life, stratified by THPC service. Patients who received THPC were matched 1:1 based on age, gender, year of death, and propensity score with those who did not receive THPC. A total of 773 cancer patients passed away in a regional hospital in Taiwan during the period of 2012-2020, of which 293 received THPC. We measured the rates and costs of outpatient clinic visits, emergency department (ED) visits, hospitalizations, and intensive care unit (ICU) admissions during the last week, the last two weeks and the last month before death. In addition, we estimated the driving times and expenses required for transportation from each cancer patient's home to the hospital using Google Maps. National Health Insurance (NHI) reimbursements and out-of-pocket expenses were also calculated. In comparison with patients without THPC, those who received THPC had a 50% lower likelihood of visiting the ED or being hospitalized, a more than 90% reduced chance of ICU admission, but were four times more likely to obtain their medicines from outpatient clinics. THPC patients had similar out-of-pocket expenditures, approximately half of the NHI costs, and lower rates and costs for ambulance transportation to the ED. THPC reduced health care costs for terminal cancer patients in the last week, the last two weeks, and the last month before death, while also increasing the likelihood of patients being able to rest and pass away at home.

2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It is synthesized on demand in postsynaptic membranes through the sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) and diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations of PLC and DAGL isoforms, as well as additional intracellular pathways implying other enzymes and substrates. Three other alternative pathways of 2-AG synthesis rest on the extracellular cleavage of 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), and two members of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6-7). We propose the names of AlterAG-1, -2, and -3 for three pathways sharing an ectocellular localization, allowing them to convert extracellular lysophospholipid mediators into 2-AG, thus inducing typical signaling switches between various G-protein-coupled receptors (GPCRs). This implies the critical importance of the regioisomerism of both lysophospholipid (LPLs) and 2-AG, which is the object of deep analysis within this review. The precise functional roles of AlterAGs are still poorly understood and will require gene invalidation approaches, knowing that both 2-AG and its related lysophospholipids are involved in numerous aspects of physiology and pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders.

Radiomics provided opportunities to quantify the tumor phenotype non-invasively. This study extracted contrast-enhanced computed tomography (CECT) radiomic signatures and evaluated clinical features of bone metastasis in non-small-cell lung cancer (NSCLC). With the combination of the revealed radiomics and clinical features, the predictive modeling on bone metastasis in NSCLC was established.

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) impacting cognitive function in long-term testicular cancer survivors (TC-survivors). TC-survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those which assessed cognition. Medical record abstraction provided cancer and treatment history. Multivariable logistic regression examined relationships between potential associated factors and cognitive impairment. Among 678 TC-survivors [median age: 46 (IQR: 38, 54); median time-since-chemotherapy: 10.9 years (IQR = 7.9, 15.9)], 13.7% reported cognitive dysfunction. Hearing loss (OR = 2.02; P = .040), neuropathic-pain (OR = 2.06; P = .028), fatigue (OR = 6.11; P<.001), and anxiety/depression (OR = 1.96; P = .029) were associated with cognitive impairment in multivariable analyses. Being on disability (OR = 9.57; P = .002) or retired (OR = 3.64; P = .029) were also associated with cognitive declines. Factors associated with impaired cognition identify TC-survivors requiring closer monitoring, counseling, and focused interventions. Hearing loss, neuropathic-pain, fatigue, and anxiety/depression constitute potential targets for prevention or reduction of cognitive impairment in long-term TC-survivors.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Hematopoietic stem cell transplantation (HCT) is an intensive and invasive procedure used in cancer treatment that can lead to posttraumatic stress disorder (PTSD) symptoms. These symptoms are frequently overlooked in oncology and general health care settings. The suitability and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) within the cancer population remains uncertain. This study aims to evaluate its performance as a brief (five-item) case-finding screening alternative to the longer (20-item) PTSD Checklist for DSM-5 (PCL-5) in survivors who received an HCT 1 to 5 years ago.

Genome-wide association studies (GWAS) implicate broad genomic loci containing clusters of highly correlated genetic variants. Finemapping techniques can select and prioritize variants within each GWAS locus which are more likely to have a functional influence on the trait. Here, we present a novel method, Finemap-MiXeR, for finemapping causal variants from GWAS summary statistics, controlling for correlation among variants due to linkage disequilibrium. Our method is based on a variational Bayesian approach and direct optimization of the Evidence Lower Bound (ELBO) of the likelihood function derived from the MiXeR model. After obtaining the analytical expression for ELBO's gradient, we apply Adaptive Moment Estimation (ADAM) algorithm for optimization, allowing us to obtain the posterior causal probability of each variant. Using these posterior causal probabilities, we validated Finemap-MiXeR across a wide range of scenarios using both synthetic data, and real data on height from the UK Biobank. Comparison of Finemap-MiXeR with two existing methods, FINEMAP and SuSiE RSS, demonstrated similar or improved accuracy. Furthermore, our method is computationally efficient in several aspects. For example, unlike many other methods in the literature, its computational complexity does not increase with the number of true causal variants in a locus and it does not require any matrix inversion operation. The mathematical framework of Finemap-MiXeR is flexible and may also be applied to other problems including cross-trait and cross-ancestry finemapping.

: : To provide contemporary data on cancer mortality rates within the context of incidence in the population with intellectual disabilities. : : Scotland's 2011 Census was used to identify adults with intellectual disabilities and controls with records linked to the Scottish Cancer Registry and death certificate data (March 2011-December 2019). The control cohort without intellectual disabilities and/or autism were used for indirect standardisation and calculation of crude incident rates/crude mortality rates, and age-sex standardised incident rate ratios/standardised mortality ratios (SIR/SMR), with 95% CIs. : : Adults with intellectual disabilities were most likely diagnosed cancers of digestive, specifically colorectal (14.2%), lung (9.3%), breast (female 22.9%), body of the uterus (female 9.3%) and male genital organs (male 17.6%). Higher incident cancers included metastatic cancer of unknown primary origin (female SIR=1.70, male SIR=2.08), body of uterus (female SIR=1.63), ovarian (female SIR=1.59), kidney (female SIR=1.85) and testicular (male SIR=2.49). SMRs were higher, regardless of a higher, similar or lower incidence (female SMR=1.34, male SMR=1.07). Excess mortality risk was found for colorectal (total SMR=1.54, male SMR=1.59), kidney (total SMR=2.01 u, female SMR=2.85 u), female genital organs (SMR=2.34 (ovarian SMR=2.86 u, body of uterus SMR=2.11), breast (female SMR=1.58) and metastatic cancer of unknown primary origin (female SMR=2.50 u, male SMR=2.84). : : Adults with intellectual disabilities were more likely to die of cancer than the general population. Reasons for this may include later presentation/diagnosis (so poorer outcomes), poorer treatment/compliance or both. Accessible public health approaches are important for people with intellectual disabilities, and healthcare professionals need to be aware of the different cancer experiences faced by this population.

Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer.

To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties.

Exploring changes in the intrinsic activity of the brain in people with bipolar disorder (BD) is necessary. However, the findings have not yet led to consistent conclusions. In this regard, this paper aims to extract more obvious differential brain areas and neuroimaging markers, for the purpose of providing assistance for early clinical diagnosis and subsequent treatment. We conducted a meta-analysis of whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) studies using seed-based d-mapping software that examined differences in amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) between patients with BD and healthy controls (HCs). Seed-based d-Mapping (formerly Signed Differential Mapping) with Permutation of Subject Images, or SDM-PSI, is a statistical technique for meta-analyzing studies of differences in brain activity or structure. A total of 16 articles involving 1112 individuals were included in this study for meta-analysis. This paper confidently analyzes the correlation between the clinical scales HAMD, HAMA, and YMRS, and the area of difference. We found significant changes that increased activation in the anterior connective and left lens nucleus, the nucleus of the shell, and BA 48 in BD patients compared with HC (P < 0.05, uncorrected), as well as a significant correlation between HAMD and the left superior frontal gyrus (after FWE correction P < 0.05). Therefore, basal ganglia and frontal cortex may have important significance in the pathogenesis and pathological basis of BD, making it an important issue to be attached importance to.

Consumer genomic testing (CGT), including direct-to-consumer and consumer-initiated testing, is increasingly widespread yet has limited regulatory oversight. To assess the current state, we surveyed genetics healthcare providers' experiences with CGT.

This study explores the association between LE8 scores and mortality risks among individuals diagnosed with cardiovascular disease (CVD). Utilizing data from the NHANES conducted between 2005 and 2018, survey-weighted multivariable Cox proportional hazards regression models were utilized. Life's Essential 8 (LE8) scores dose-response associations were assessed using restricted cubic spline regression. Sub-analyses were performed for different categories of CVD. The study consisted of 2164 participants diagnosed with CVD, ranging in age from 20 to 80 years (weighted mean [SE] age, 61.47 [0.34] years; The average total LE8 was 64.97 [0.54]. 499 participants experienced mortality, with 350 deaths attributed to CVD. After accounting for potential covariates, LE8 score was found to be associated with a decreased both all-cause mortality (OR 0.34, CI 0.22-0.51) and CVD mortality (OR 0.40, CI 0.23-0.68). A survey-weighted multivariable Cox model with restricted cubic splines identified the lowest all-cause mortality (P < 0.001) and CVD mortality (P < 0.001) risk when LE8 reach at 63.75 (P < 0.001). The results highlight the association between LE8 scores and reduced mortality in CVD patient population. The implementation of comprehensive initiatives that prioritize healthy dietary patterns, will play a crucial role in alleviating the impact of cardiovascular disease and improving cardiovascular health outcomes.

Circulating plasma proteins play key roles in human health and can potentially be used to measure biological age, allowing risk prediction for age-related diseases, multimorbidity and mortality. Here we developed a proteomic age clock in the UK Biobank (n = 45,441) using a proteomic platform comprising 2,897 plasma proteins and explored its utility to predict major disease morbidity and mortality in diverse populations. We identified 204 proteins that accurately predict chronological age (Pearson r = 0.94) and found that proteomic aging was associated with the incidence of 18 major chronic diseases (including diseases of the heart, liver, kidney and lung, diabetes, neurodegeneration and cancer), as well as with multimorbidity and all-cause mortality risk. Proteomic aging was also associated with age-related measures of biological, physical and cognitive function, including telomere length, frailty index and reaction time. Proteins contributing most substantially to the proteomic age clock are involved in numerous biological functions, including extracellular matrix interactions, immune response and inflammation, hormone regulation and reproduction, neuronal structure and function and development and differentiation. In a validation study involving biobanks in China (n = 3,977) and Finland (n = 1,990), the proteomic age clock showed similar age prediction accuracy (Pearson r = 0.92 and r = 0.94, respectively) compared to its performance in the UK Biobank. Our results demonstrate that proteomic aging involves proteins spanning multiple functional categories and can be used to predict age-related functional status, multimorbidity and mortality risk across geographically and genetically diverse populations.

The aim of this study was to understand the experiences of young men with a diagnosis of testicular cancer (TC) using a narrative approach, with the intention of informing models of care and support in clinical services.

Adolescent and young adult (AYA) patients with cancer often demonstrate suboptimal engagement in cancer care due to a host of logistical, developmental, and psychological factors. This clinical case study of a young adult (YA) with cancer highlights the multiple ways in which social anxiety disorder (SAD) impacted a YA's engagement in cancer care. The case study also details the use of an evidence-based treatment for SAD to support behavioral change. Identification and receipt of timely evidence-based psychological intervention for SAD have the potential to improve AYA well-being and enhance cancer care engagement.

Organoselenium (OSe) agents and Schiff bases have demonstrated immense potential in the pharmaceutical field due to their broad spectrum of medicinal activities.

To understand multidisciplinary healthcare clinicians' meaningful and challenging experiences providing spiritual care to patients with cancer and their care partners.

Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older.

To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD).

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.

Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively-measured physical activity, cognition, and inflammation in older breast cancer survivors.

Intellectual disability liaison nurses in general hospitals could enhance access to high-quality, adapted healthcare and improve outcomes. We aimed to explore associations between the input of intellectual disability liaison nurses and the quality of care in people with intellectual disability who are admitted to hospital.

Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child's pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement.

The aim of the study was to determine the effect of WhatsApp-based BETTER sex counselling on sexual function and sexual quality of life in breast cancer survivors in a randomized control trial.

Cushing's disease (CD) represents a state of cortisol excess, serving as a model to investigate the effects of prolonged hypercortisolism on functional brain. Potential alterations in the functional connectome of the brain may explain frequently reported cognitive deficits and affective disorders in CD patients. This study aims to elucidate the effects of chronic hypercortisolism on the principal functional gradient, which represents a hierarchical architecture with gradual transitions across cognitive processes, by integrating connectomics and transcriptomics approaches. Utilizing resting-state functional magnetic resonance imaging data from 140 participants (86 CD patients, 54 healthy controls) recruited at a single center, we explored the alterations in the principal gradient in CD patients. Further, we thoroughly explored the underlying associative mechanisms of the observed characteristic alterations with cognitive function domains, biological attributes, and neuropsychiatric representations, as well as gene expression profiles. Compared to healthy controls, CD patients demonstrated changes in connectome patterns in both primary and higher-order networks, exhibiting an overall converged trend along the principal gradient axis. The gradient values in CD patients' right prefrontal cortex and bilateral sensorimotor cortices exhibited a significant correlation with cortisol levels. Moreover, the cortical regions showing gradient alterations were principally associated with sensory information processing and higher-cognitive functions, as well as correlated with the gene expression patterns which involved synaptic components and function. The findings suggest that converged alterations in the principal gradient in CD patients may mediate the relationship between hypercortisolism and cognitive impairments, potentially involving genes regulating synaptic components and function.

Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.

Advancements in cancer treatment and survivorship rely on participation in research and access to health records.

Melanin is a crucial pigment in melanomagenesis. Its fluorescence in human tissue is exceedingly weak but can be detected through advanced laser spectroscopy techniques. The spectral profile of melanin fluorescence distinctively varies among melanocytes, nevomelanocytes, and melanoma cells, with melanoma cells exhibiting a notably "red" fluorescence spectrum. This characteristic enables the diagnosis of melanoma both in vivo and in histological samples. Neuromelanin, a brain pigment akin to melanin, shares similar fluorescence properties. Its fluorescence can also be quantified with high spectral resolution using the same laser spectroscopic methods. Documented fluorescence spectra of neuromelanin in histological samples from the substantia nigra substantiate these findings. Our research reveals that the spectral behavior of neuromelanin fluorescence mirrors that of melanin in melanomas. This indicates that the typical red fluorescence is likely influenced by the microenvironment around (neuro)melanin, rather than by direct pigment interactions. Our ongoing studies aim to further explore this distinctive "red" fluorescence. We have observed this red fluorescence spectrum in post-mortem measurements of melanin in benign nevus. The characteristic red spectrum is also evident here (unlike the benign nevus in vivo), suggesting that hypoxia may contribute to this phenomenon. Given the central role of hypoxia in both melanoma development and treatment, as well as in fundamental Parkinson's disease mechanisms, this study discusses strategies aimed at reinforcing the hypothesis that red fluorescence from (neuro)melanin serves as an indicator of hypoxia.

The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1 cells expressing canonical astrocytic markers including ALDOC, NFIA, GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans.

Central nervous system (CNS) injury following brain-directed radiotherapy remains a major challenge. Proton radiotherapy (PRT) minimizes radiation to healthy brain, potentially limiting sequelae. We characterized CNS radiotoxicity, including radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), in glioma patients treated with PRT or photons (XRT).

To quantify the risk of long-term post-radical prostatectomy (RP) erectile dysfunction (ED) in men with diabetes mellitus (DM).

This study aimed to explore whether the Discrepancy between the desired time in Bed and the desired total Sleep Time (DBST) index influences insomnia severity in the older adult population and examined the potential role of psychological inflexibility in this association.

Cigarettes with higher levels of filter ventilation are misperceived as less harmful and may be more appealing to consumers. Setting limits on filter ventilation has been considered as a policy, but a better understanding of any potential unintended consequences is needed.

To identify childhood cancer patients and their families at the greatest risk for psychosocial difficulties, this study examined the predictive validity of the Psychosocial Assessment Tool 2.0 (PAT2.0) on caregiver and patient-reported mental health outcomes at 1-year follow-up. The PAT2.0 was administered to caregivers a median of 0.08 years after cancer diagnosis. A brief psychosocial screening battery (Family Symptom Inventory and PROMIS v1.0 Pediatric Profile-25) was administered to patient-caregiver dyads (n=53) ∼1-year later. Linear regressions support the longitudinal predictive validity of the PAT2.0 for caregiver-reported child and caregiver mental health symptoms and child-reported peer relationships difficulties.

Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.

Prescription opioids are used for managing pain in persons with cancer, however, there are socioeconomic and racial disparities in medication access. Cannabis is increasingly used for cancer symptom management and as an opioid alternative. Limited data are available about patterns of opioid and cannabis use among patients with cancer. We used survey data from 4 National Cancer Institute-designated cancer centers in 3 states (n = 1220) to assess perceptions, use of cannabis and opioids for pain, their substitution, and racial and ethnic differences in each outcome. Compared with White patients, Black patients were less likely to use opioids for pain (odds ratio [OR] = 0.66; P = .035) and more likely to report that cannabis was more effective than opioids (OR = 2.46; P = .03). Race effects were mitigated (P > .05) after controlling for socioeconomic factors. Further research is needed to understand cannabis and opioid use patterns and how overlapping social determinants of health create a disadvantage in cancer symptom management for Black patients.

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk.

We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC).

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs.

Peptides that form transmembrane barrel-stave pores are potential alternative therapeutics for bacterial infections and cancer. However, their optimization for clinical translation is hampered by a lack of sequence-function understanding. Recently, we have designed the first synthetic barrel-stave pore-forming antimicrobial peptide with an identified function of all residues. Here, we systematically mutate the peptide to improve pore-forming ability in anticipation of enhanced activity. Using computer simulations, supported by liposome leakage and atomic force microscopy experiments, we find that pore-forming ability, while critical, is not the limiting factor for improving activity in the submicromolar range. Affinity for bacterial and cancer cell membranes needs to be optimized simultaneously. Optimized peptides more effectively killed antibiotic-resistant ESKAPEE bacteria at submicromolar concentrations, showing low cytotoxicity to human cells and skin model. Peptides showed systemic anti-infective activity in a preclinical mouse model of infection. We also demonstrate peptide optimization for pH-dependent antimicrobial and anticancer activity.

Inflammation and synapse loss have been associated with deficits in social behavior and are involved in pathophysiology of many neuropsychiatric disorders. Synapse loss, characterized by reduction in dendritic spines can significantly disrupt synaptic connectivity and neural circuitry underlying social behavior. Chronic stress is known to induce loss of spines and dendrites in the prefrontal cortex (PFC), a brain region implicated in social behavior. However, the underlying mechanisms are not well understood. In the present study, we investigated the role of type I Interferon (IFN-I) signaling in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found increased expression of type I IFN receptor (IFNAR) in microglia following CUS. Conditional knockout of microglial IFNAR in adult mice rescued CUS-induced social behavior deficits and synapse loss. Bulk RNA sequencing data show that microglial IFNAR deletion attenuated CUS-mediated changes in the expression of genes such as Keratin 20 (Krt20), Claudin-5 (Cldn5) and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. Cldn5 and Nr4a1 are known for their roles in synaptic plasticity. Krt20 is an intermediate filament protein responsible for the structural integrity of epithelial cells. The reduction in Krt20 following CUS presents a novel insight into the potential contribution of cytokeratin in stress-induced alterations in neuroplasticity. Overall, these results suggest that microglial IFNAR plays a critical role in regulating synaptic plasticity and social behavior deficits associated with chronic stress conditions.

This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM) and < 10 µm (PM) in an aerodynamic diameter], nitrogen dioxide (NO), ozone (O), carbon monoxide (CO), and sulfur dioxide (SO) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants.

Cancer treatment-related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI.

Cannabis use is prevalent among cancer patients and survivors and may provide some therapeutic benefits for this population. However, benefits may be attenuated when cannabis is co-used with tobacco, which is associated with more severe tobacco and cannabis use and adverse outcomes in noncancer populations. We compared cannabis use, primary mode of use, and therapeutic and/or nontherapeutic use among 3 groups of patients and survivors based on cigarette smoking status.

The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis.

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer.

This study investigated whether the discrepancy between desired time in bed and desired total sleep time (DBST) index could be a meaningful indicator for assessing insomnia severity in a clinical sample of patients with insomnia. Furthermore, we sought to identify the mediators of the association between DBST and insomnia severity in individuals with insomnia.

Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD.

The psychiatric needs of those with cancer and other advanced illnesses are becoming increasingly recognized. Ketamine is emerging as a promising treatment option for depressive disorders in psychiatric and palliative care. In the palliative care setting, its study has been hindered by lack of consistent administration routes and dosing. Intranasal (IN) esketamine (Spravato) has recently received U.S. Food and Drug Administration (FDA) approval as an adjunctive agent for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation (SI). We sought to offer IN esketamine to patients suffering from TRD and SI at a comprehensive cancer center. We designed and implemented a protocol to administer IN esketamine and describe three cases in which it was provided to patients with TRD and SI at a palliative care clinic in the United States. Following treatment, all three patients had substantial reduction in depression severity and no further suicidalideation. These improvements were maintained for up to a year. No serious adverse events occurred. These cases illustrate the potential utility of IN esketamine in the palliative care setting.

The benefits of cannabis in symptom management among cancer survivors are widely acknowledged; however, patterns of cannabis use by cancer stage at diagnosis are unknown.

Many patients with cancer use cannabis to help alleviate untreated cancer symptoms and side effects.

India has the highest number of estimated deaths from cervical cancer globally, with most cases attributed to Human papillomavirus (HPV). The World Health Organization recommends primary HPV vaccination for girls ages 9-14, with catch-up vaccination for young women ≥ 15 if feasible. India authorized a new, inexpensive HPV vaccine in 2022; given anticipated vaccine expansion, we conducted a mixed-methods study exploring acceptability of HPV catch-up vaccination for young emerging adult women in rural Mysore, India.

People with a substance use disorder (SUD) have shortened lifespans due to complications from their substance use and challenges engaging with traditional health care settings and institutions. This impact on life expectancy is especially prominent in patients with co-occurring SUDs and cancer, and often has a much worse prognosis from the cancer than a similar patient without a SUD. Palliative care teams are experts in serious illness communication and symptom management and have become increasingly embedded in the routine care of patients with cancer. We argue that the skill set of palliative care teams is uniquely suited for addressing the needs of this oft marginalized group. We provide a comprehensive review of tools for addressing these needs, including medications that can both treat pain and opioid use disorder (OUD), and highlight psychosocial approaches to treating patients with OUD and cancer in a way that is respectful and effective. Using a trauma informed framework, we focus on the application of harm reduction principles from addiction medicine and the principles of clear communication, accompaniment, and emotional presence from palliative care to maximize support. We also focus on ways to reduce stigma in the delivery of care, by providing language that reduces barriers and increases patient engagement. Finally, we describe a clinic embedded within our institution's cancer center which aims to serve patients with cancer and SUDs, built on the framework of harm reduction, accompaniment and trauma informed care (TIC). Overall, we aim to provide context for addressing the common challenges that arise with patients with cancer and OUD, including the direct impact of psychosocial stress on substance use and cancer treatment, delays in disease directed treatment that can potentially impact further treatment options and outcomes, challenging pain management due to greater opioid debt, and potential loss of primary coping mechanism through substance use in the face of potential terminal diagnosis.

Sleep difficulties and misuse of drugs/alcohol have been associated with suicidal ideation in young people. Using cross-sectional representative surveys of adolescents in the United States, we conducted adjusted logistic regression modeling to assess the relationships between sleep difficulties, substance use, and suicidal ideation among adolescents with a history of depression (n = 38,418) between 2015 and 2020. Sleep difficulties were associated with thinking about (aOR=1.6,95%CI:1.3-1.9), planning (aOR=1.8,95%CI:1.2-2.6), or attempting (aOR=1.7,95%CI:1.2-2.5) suicide. In those reporting alcohol abuse/dependence, sleep difficulties were associated with attempting suicide (aOR=3.1,95%CI:1.2-8.5). In those reporting illicit drug abuse/dependence, sleep difficulties were associated with thinking about (aOR=2.1,95%CI:1.1-4.1) and attempting (aOR=2.2,95%CI:1.2-4.1) suicide.

The precise regulation of DNA replication is vital for cellular division and genomic integrity. Central to this process is the replication factor C (RFC) complex, encompassing five subunits, which loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. While RFC1's role in cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is known, the contributions of RFC2-5 subunits on human Mendelian disorders is largely unexplored. Our research links bi-allelic variants in RFC4, encoding a core RFC complex subunit, to an undiagnosed disorder characterized by incoordination and muscle weakness, hearing impairment, and decreased body weight. We discovered across nine affected individuals rare, conserved, predicted pathogenic variants in RFC4, all likely to disrupt the C-terminal domain indispensable for RFC complex formation. Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression. Our integrated approach of combining in silico, structural, cellular, and functional analyses establishes compelling evidence that bi-allelic loss-of-function RFC4 variants contribute to the pathogenesis of this multisystemic disorder. These insights broaden our understanding of the RFC complex and its role in human health and disease.

The association between specific types of malignancies and the subsequent risk of dementia remains unknown.

Dealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity.

Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.

Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.

Dihydroorotate dehydrogenase (DHODH), an enzyme that plays a critical role in the pyrimidine biosynthesis, has been recognized as a promising target for the treatment of diseases that involve cellular proliferation, such as autoimmune diseases and cancers. Pharmacological inhibition of human DHODH (hDHODH) that offers a potential therapeutic strategy for the treatment in adult subjects with acute myeloid leukemia (AML) has recently been supported by phase I/II clinical trials for the treatment of patients with relapsed/refractory AML. To facilitate the development of optimized hDHODH inhibitors, the presence of an imaging probe that is able to demonstrate target engagement is critical and desirable. Brequinar is one of the most potent hDHODH inhibitors so far discovered. In this work, we use a copper-mediated radiofluorination (CMRF) strategy and compare the chemical design and radiosynthesis starting from either pinacole boronate -nitrobenzyl ester (4) or tributylstannate (tin) -nitrobenzyl ester (5), chosen for their suitability as a precursor to [F]brequinar. We report here the design, synthesis, radiolabeling and characterization of [F]brequinar, and a preliminary PET imaging study of DHODH . This study provides the strategies to create [F]brequinar, the first hDHODH inhibitor PET radiotracer, which will facilitate its use as a tool (theranostics) for hDHODH drug development and for diagnosis and monitoring therapeutic efficacy in AML and cancers.

We aimed to investigate the association of trait emotional intelligence (TEI), anxiety, depression, and quality of life (QoL) in lung cancer individuals with brain metastases receiving radiotherapy.

Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the advantage of being frequently detectable through oropharyngeal visual examination and having much higher survival rates than classic oropharyngeal cancers. It has been demonstrated that gay and bisexual men can take smartphone oropharyngeal "selfies" of sufficient quality for screening. However, there is an issue with the inability to move the tongue to allow a clear view of the palatine tonsils, where a majority of oropharyngeal cancer cases occur. We attempted to investigate the feasibility of using commercially available videoscopes to visualize the oropharynx. Fourteen healthy volunteers used a provided low-cost commercial endoscope to video their oropharynx. Participants used the videoscope connected to a laptop and could visualize the oropharynx on the screen. Attempts were observed, and the process was noted. A focus group of participants was carried out immediately afterwards to ascertain barriers and facilitators to using the videoscopes. All participants were able to use the videoscope and obtain videos of sufficient clarity to note major oropharyngeal landmarks. The palatine tonsils were initially difficult to visualize because the tongue could not be sufficiently controlled. Participants were given time to practice using visual cues to control the position of the tongue, which helped in obtaining good videos. Videoscopes can be used effectively with minimal instruction and provide a better view than still images, as they illuminate and magnify the site. Low-cost commercially available videoscopes may be an improvement over smartphone "selfies".

Psycho-oncological support (POS) and psychopharmacological interventions are effective in treating psychiatric symptoms in patients with breast cancer. However, despite high prevalences of psychiatric disorders in patients with breast cancer, a significant proportion remains untreated.

Very few studies have compared different diagnostic approaches to diagnose depression in patients with cancers.

Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas.

Opt2Move is a theory-guided moderate and vigorous physical activity (MVPA) promotion trial that uses multiphase optimization strategy (MOST) methodology to evaluate the individual and combined effects of four intervention components in a full factorial experiment among young adult cancer survivors (YACS; N = 304). All participants will receive the core mHealth MVPA intervention, which includes a Fitbit and standard self-monitoring Opt2Move smartphone application. YACS will be randomized to one of 16 conditions to receive between zero and four additional components each with two levels (yes v. no): E-Coach, buddy, general mindfulness, and MVPA-specific mindfulness.

In the United States, the Food and Drug Administration (FDA) requires tobacco product manufacturers to submit Premarket Tobacco Product Applications (PMTA) for new products, granting marketing approval only if deemed appropriate for the protection of public health. Historically, the tobacco industry has exploited loopholes in the Tobacco Control Act (TCA), especially related to the definitions of nicotine, tobacco product and characterizing flavors, to circumvent the PMTA requirement. In 2023, the industry introduced several 'PMTA-exempt' e-cigarette and smokeless products, including products containing 6-methyl nicotine, a synthetic nicotine analog that is pharmacologically more potent than nicotine. In late 2023 and early 2024, the major US e-cigarette suppliers Nicotine River and ECBlend introduced 'PMTA-exempt' products with the brand names 'Nixamide' or 'Nixodine' or 'Nixotine', with nicotinamide as the main active ingredient. Nicotinamide is a form of vitamin B3 with no known pharmacological activity at nicotinic receptors. Here, we report that the marketing claims for these products, suggesting them and be nicotine substitute products designed to target nicotinic receptors and provide the same experience as nicotine, is deceptive and misleading to consumers. We also inform that these products have evolved further to contain a combination of nicotinamide and 6-methyl nicotine. The regulatory implications of these newly introduced products are discussed.

The World Health Organisation's vision of eliminating cervical cancer as a public health problem is achievable, but elimination must be achieved equitably, including for people with intellectual disability. A better understanding of cervical screening within the context of the lives of people with intellectual disability is needed. This study systematically reviewed research on the rates of cervical screening participation among people with intellectual disability, and facilitators and barriers that affect participation.

Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear.

Psychedelics are receiving growing interest among clinical researchers for their effects on mood and cognition. Psilocybin is one of the most widely studied classic psychedelics which has shown good safety and clinical benefit for major depression and substance use disorders. Athletes frequently sustain concussions and often experience myriad symptoms, including cognitive and mood issues, which can persist for weeks or months in 10%-30% of athletes. Psilocybin may be a potential symptom management option for athletes with persisting concussion symptoms.

Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT leads to altered testosterone levels that may affect brain morphology as well as cognition. Considering the reliability of cortical thickness (CT) as a marker of cognitive and brain changes, e.g., in Alzheimer's disease, we assessed the impacts of ADT on CT and working memory. Thirty men with non-metastatic prostate cancer receiving ADT and 32 patients not receiving ADT (controls or CON), matched in age and years of education, participated in N-back task and quality-of-life (QoL) assessments as well as brain imaging at baseline and prospectively at 6 months. Imaging data were processed with published routines to estimate CT and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. ADT and CON did not differ in N-back performance or QoL across time points. Relative to CON, patients receiving ADT showed significantly higher frontopolar cortex (FPC) CT at 6-month follow-up vs. baseline. Follow-up vs. baseline FPC CT change correlated negatively with changes in 2-back correct response rate and in testosterone levels across all participants. In mediation analysis, FPC CT change mediated the association between testosterone level change and 2-back accuracy rate change. Increases in FPC CT following 6 months of ADT may reflect early neurodegenerative changes in response to androgen deprivation. While no significant impact on working memory or QoL was observed over 6 months, further research of longer duration of treatment is warranted to unravel the full spectrum of cognitive and neural consequences of ADT in prostate cancer patients.

The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC).

Gynecological cancers are prevalent malignancies among females, and surgical intervention is the primary therapeutic approach offering the possibility of a definitive cure. Recent research has highlighted the susceptibility of gynecological cancer patients to experiencing anxiety symptoms during the perioperative and postoperative phases, with this psychological condition being linked to suboptimal recovery following surgery. Nevertheless, certain interventions have shown promise in mitigating perioperative and postoperative anxiety in gynecological cancer patients. In this study, we conducted a comprehensive review to collect the existing evidence on this subject. Through a systematic search across six common databases, we screened and included 28 pertinent studies. The current review emphasizes the elevated occurrence of perioperative and postoperative anxiety among patients with gynecological cancers (i.e., uterine, cervical, ovarian, endometrial, and vulval cancers). Specific nursing interventions (i.e., crisis intervention nursing, multidisciplinary collaborative continuous nursing, psychological nursing, comprehensive psychological nursing, reminiscence therapy involved care, cognitive behavioral stress management, hospital-family integrated continuation nursing, high-quality nursing care, relaxation-focused nursing program, and relaxation/counseling intervention) and psychotropic medications may serve as dependable approaches to mitigate perioperative and postoperative anxiety. This study represents a novel contribution to the literature by providing a characterization of perioperative and postoperative anxiety in the context of gynecological oncology. The findings underscore the significance of addressing perioperative and postoperative anxiety as a critical clinical concern for individuals with gynecological cancers, emphasizing the need for further research to develop effective interventions.

The prevalence of severe mental disorders has been rising annually. Electroconvulsive therapy (ECT) is considered a valuable treatment option in psychiatry for conditions such as schizophrenia and medication-resistant depression, especially when other treatments have proven insufficient. ECT rapidly improves patients' mood, alleviates symptoms, and demonstrates significant therapeutic effects. Currently, the form of ECT used in clinical practice is modified electroconvulsive therapy (mECT), which is administered under general anesthesia. Accumulative evidence has confirmed that different anesthetic drugs, anesthetic-ECT time interval, anesthetic depth, and airway management can impact the outcomes of ECT. Therefore, this review aims to summarize the current impact of anesthesia factors on ECT, providing reference for clinical anesthesia during ECT procedures.

Patients diagnosed with Parkinson's disease undergo alterations in physical, psychological, and social functionality, with the psychological domain being particularly predisposed to inducing fatigue and depressive symptoms. Understanding the alterations occurring within a patient's body and mind and how these influence their overall quality of life is crucial.