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Assessment of the degree of impaired autonomic nervous system (ANS) function is not part of routine clinical practice during inpatient rehabilitation following traumatic spinal cord injury (SCI). The goal of this investigation was to determine the utility of the International Standards for Neurologic Classification of SCI (ISNCSCI) and the recently revised International Standards to document remaining Autonomic Function after SCI (ISAFSCI) in documenting cardiovascular ANS impairment during inpatient rehabilitation following traumatic SCI. Beat-to-beat recording of supine heart rate (HR) and blood pressure (BP) were collected at the bedside for estimation of total cardiovascular ISAFSCI score, cardio-vagal modulation (i.e., high frequency HR variability [HF

Social media become an important space where people receive and share up-to-date health-related information during the rapid global spread of the novel coronavirus (COVID-19). While information sharing in social media has been shown to improve relations, reduce stress, and enhance life satisfaction, little is known about reciprocal sharing. Situated in COVID-19 pandemic, this study conceptualizes information sharing as a communication process during which sharers expect the receivers to reciprocate, while receivers feel obligated to return the favor. Building upon social exchange theory and studies on social media sharing, the study tested a model of moderated mediation in which sharing of COVID-19 information was predicted to enhance life satisfaction by encouraging reciprocal sharing, i.e., information reciprocity. Subjective norms, attitudes, and perceived usefulness of the information was predicted to moderate the mediation. The hypothesized mediation was supported by data from a survey of 511 online participants in China. Furthermore, the indirect effect appeared stronger among the respondents who found the information more useful, reported more positive attitude, or perceived more subjective norms. The findings suggest that expected reciprocation may be an important incentive for social sharing, and received reciprocation may be a central part of the mechanism through which sharing benefits the sharer. Policymakers and communicators may need to take information reciprocity into consideration when designing health information campaign to confront communal threats.

Due to separation from their families and friends in their home countries and constrained living conditions in the host countries, migrant workers usually are found to experience loneliness. Compared with male migrant workers, female migrant workers are more vulnerable and likely to experience higher levels of psychological problems. The ubiquity of mobile phones enables migrant workers to access resources and social support to help to alleviate loneliness. However, research also suggests that mobile phone use may lead to a higher level of loneliness because problematic or excessive use displaces meaningful social interactions. This study investigates this mobile phone paradox among Filipino domestic workers (FDWs) in Hong Kong. Specifically, it explores the relationships between mobile phone use and two types of loneliness, namely social and emotional loneliness. Further, informed by the augmentation hypothesis and the displacement hypothesis, this research advances a two-path model to illustrate how mobile phone use connects with loneliness through social support and problematic mobile phone use. Findings from a survey of 492 FDWs reveal disjunctive effects. There is no direct correlation between mobile phone use and the two types of loneliness. Both problematic mobile phone use and social support are found to mediate the negative association between mobile phone use and social loneliness, while only problematic mobile phone use mediates the positive association between mobile phone use and emotional loneliness. Implications of the research on migrant workers’ mobile phone use and practical implications for social work and government efforts in helping FDWs dealing with loneliness are discussed.

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Purpose:The third-generation EGFR inhibitor, osimertinib, is the first mutant-selective inhibitor that has received regulatory approval for the treatment of patients with EGFR-mutant lung cancer. Despite the development of highly selective third-generation inhibitors, acquired resistance remains a significant clinical challenge. Recently, we and others have identified a novel osimertinib resistance mutation, G724S, which was not predicted in in vitro screens. Here, we investigate how G724S confers resistance to osimertinib.Experimental Design: We combine structure-based predictive modeling of G724S in combination with the 2 most common EGFR-activating mutations, exon 19 deletion (Ex19Del) and L858R, with in vitro drug-response models and patient genomic profiling.Results:Our simulations suggest that the G724S mutation selectively reduces osimertinib-binding affinity in the context of Ex19Del. Consistent with our simulations, cell lines transduced with Ex19Del/G724S demonstrate resistance to osimertinib, whereas cells transduced with L858R/G724S are sensitive to osimertinib. Subsequent clinical genomic profiling data further suggest G724S occurs with Ex19Del but not L858R. Furthermore, we demonstrate that Ex19Del/G724S retains sensitivity to afatinib, but not to erlotinib, suggesting a possible therapy for patients at the time of disease relapse.Conclusions:Altogether, these data suggest that G724S is an allele-specific resistance mutation emerging in the context of Ex19Del but not L858R. Our results fundamentally reframe the problem of targeted therapy resistance from one focused on the “drug–resistance mutation” pair to one focused on the “activating mutation–drug–resistance mutation” trio. This has broad implications across clinical oncology.

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Inherited genetic variation profoundly influences cancer risk and outcome. While the impact of germline single nucleotide polymorphisms has been well-studied in several cancer types, the effects of germline structural variants (gSVs) on cancer biology and clinical outcomes is largely unknown. From our cohort of 300 men with localized, intermediate risk prostate cancer, we identified 6,003 gSVs present in at least 3% of patients; 48 were associated with recurrent somatic alterations or clinical outcome. Of these, approximately 50% were associated with expression of nearby genes or intersected with exons or regulatory regions. Using external cohorts, we validated three gSVs that were strongly associated with poor clinical outcomes, including an inversion at chr14q24.1 present in ~20% of patients. Notably, a strong synergistic effect on outcome was observed in patients with somatic TP53 alterations or high genomic instability, defining a new aggressive prostate cancer subtype with chr14INV as a novel, recurrent biomarker. Citation Format: Nicholas K. Wang, Alexandre Rouette, Kathleen E. Houlahan, Takafumi N. Yamaguchi, Julie Livingstone, Chol-Hee Jung, Peter Georgeson, Michael Fraser, Yu-Jia Shiah, Cindy Q. Yao, Vincent Huang, Natalie S. Fox, Natalie Kurganovs, Katayoon Kasaian, Veronica Y. Sabelnykova, Jay Jayalath, Kenneth Weke, Helen Zhu, Theodorus van der Kwast, Tony Papenfuss, Housheng H. He, Niall M. Corcoran, Robert G. Bristow, Alexandre R. Zlotta, Christopher Hovens, Paul C. Boutros. Germline structural variants shape prostate cancer clinical and molecular evolution. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4305.

Objectives The objective of this study is to elucidate the impact of income on short-term outcomes in a cerebellopontine angle (CPA) tumor resection population. Design This is a retrospective regression analysis. Setting This study was done at a single, multihospital, urban academic medical center. Participants Over 6 years (from June 7, 2013, to April 24, 2019), 277 consecutive CPA tumor cases were reviewed. Main Outcome Measures Outcomes studied included readmission, emergency department evaluation, unplanned return to surgery, return to surgery after index admission, and mortality. Univariate analysis was conducted among the entire population with significance set at a p-value Results Regression analysis of 273 patients demonstrated decreased rates of unplanned reoperation (p = 0.015) and reoperation after index admission (p = 0.035) at 30 days with higher standardized income. Logistic regression between the lowest (Q1) and highest (Q4) socioeconomic quartiles demonstrated decreased unplanned reoperation (p = 0.045) and decreasing but not significant reoperation after index admission (p = 0.15) for Q4 patients. No significant difference was observed for other metrics of morbidity and mortality. Conclusion Higher socioeconomic status is associated with decreased risk of unplanned reoperation following CPA tumor resection.

The application of Markov chains to modelling refugee crises is explored, focusing on local migration of individuals at the level of cities and days. As an explicit example, we apply the Markov chains migration model developed here to United Nations High Commissioner for Refugees data on the Burundi refugee crisis. We compare our method to a state-of-the-art ‘agent-based’ model of Burundi refugee movements, and highlight that Markov chain approaches presented here can improve the match to data while simultaneously being more algorithmically efficient.

Suicide and depression among orthopaedic surgeons have recently emerged as rising concerns. Prior research has suggested that orthopaedic surgeons have the highest prevalence of suicide among surgical specialties. We sought to determine the factors associated with depression and suicidal ideation (SI) in orthopaedics, including subspecialty.A survey including demographic questions, the Beck Depression Inventory, and the Columbia-Suicide Severity Rating Scale was administered electronically via a listserv to the orthopaedic subspecialties of trauma, adult reconstruction, hand and upper extremity, shoulder and elbow, foot and ankle, spine, pediatrics, sports medicine, and oncology. The responses were quantified according to previously published criteria. The associations of demographic factors, training, and current practice environment with depression and suicidality were assessed using Fisher exact tests. Reverse stepwise multivariable logistic regression models were developed to identify factors associated with depression and SI.The responses were obtained from 661 board-certified, practicing orthopaedic surgeons. In this study, 156 surgeons (23.6%) endorsed some level of active SI in their lifetime, 200 surgeons (30.3%) reported either active or passive SI in their lifetime, and 33 surgeons (5%) reported that, on at least 1 occasion in their lifetime, they had experienced active SI with a specific plan and intention to harm themselves. Gender, relationship status, having children, and residency and/or current practice region were significantly associated with depression and/or SI. Younger age, divorce, adult reconstruction and foot and ankle subspecialties, and attending residency in the Western U.S. were found on multivariable testing to be associated with symptoms of depression and SI (odds ratios, 1.03 [per 1-year decrease in age] to 8.28).Symptoms of depression and suicidality are not uncommon among orthopaedic surgeons, and variation by gender, relationship status, and geographic location are supported by prior research. Based on our results, depression and/or SI likely affect someone close to you or someone with whom you work. The normalization of discussions surrounding emotional well-being, depression, and SI is imperative.

Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour telomere lengths are associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling are correlated with tumour telomere length at all levels of the central dogma. Telomere length is also associated with multiple clinical features of a tumour. Longer telomere lengths in non-tumour samples are associated with a lower rate of biochemical relapse. In summary, we describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer., Despite the known role of telomere length in cancer, its association with genomic features remains unclear. Here, the authors integrate telomere length, genomics, transcriptomics and proteomics in localized prostate cancer and reveal links between telomere maintenance, disease drivers and clinical outcomes.