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Background: Young males experience markedly poorer mental health outcomes. Organised sport settings provide novel prospects to improve the mental health of this subpopulation., Aim: This systematic review aimed to evaluate interventions targeted at the promotion of mental health and wellbeing among young males in organised sporting contexts., Methods: Six databases (SportDiscus, PsycInfo, Medline, Web of Science, Scopus, CINAHL) were searched from inception to June 2022 (and updated in September 2023). Eligible studies examined interventions targeting the mental health and wellbeing (e.g., depression, anxiety, resilience) or mental health literacy (e.g., stigmatising attitudes, help-seeking) of young males aged 10-24 years (or associated stakeholder samples; e.g., parents or coaches of male youth)., Results: A total of 15 studies were included in this review. Overall, the findings indicate promising effects of sport-based interventions on the mental health and mental health literacy outcomes of young males., Conclusions: This review suggests that there is scope to improve the capacity of sports-based interventions to affect positive change in the mental health of male youth. The findings from this review also have important implications for the development and evaluation of sports-based interventions targeted at young males in future., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With the advent of machine learning (ML) and deep learning (DL) empowered applications for critical applications like healthcare, the questions about liability, trust, and interpretability of their outputs are raising. The black-box nature of various DL models is a roadblock to clinical utilization. Therefore, to gain the trust of clinicians and patients, we need to provide explanations about the decisions of models. With the promise of enhancing the trust and transparency of black-box models, researchers are in the phase of maturing the field of eXplainable ML (XML). In this paper, we provided a comprehensive review of explainable and interpretable ML techniques for various healthcare applications. Along with highlighting security, safety, and robustness challenges that hinder the trustworthiness of ML, we also discussed the ethical issues arising because of the use of ML/DL for healthcare. We also describe how explainable and trustworthy ML can resolve all these ethical problems. Finally, we elaborate on the limitations of existing approaches and highlight various open research problems that require further development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: Previous studies from the U.S. and Canada report deficiencies in informed decision making and a need to improve end-of-life (EoL) care in patients undergoing dialysis. However, there is a paucity of literature on these issues in Pakistani dialysis patients, who differ from Western patients in culture, religion, and available health care services., Objectives: To study informed dialysis decision-making and EoL attitudes and beliefs in Pakistani patients receiving dialysis., Methods: We used convenience sampling to collect 522 surveys (90% response rate) from patients in seven different dialysis units in Pakistan. We used an existing dialysis survey tool, translated into Urdu, and backtranslated to English. A facilitator distributed the survey, explained questions, and orally administered it to patients unable to read., Results: Less than one-fourth of the respondents (23%) felt informed about their medical condition, and 45% were hopeful that their condition would improve in the future. More than half (54%) wished to know their prognosis, and 80% reported having no prognostic discussion. Almost 63% deemed EoL planning important, but only 5% recalled discussing EoL decisions with a doctor during the last 12 months. Nearly 62% of the patients regretted their decision to start dialysis. Patients' self-reported knowledge of hospice (5%) and palliative care (7.9%) services was very limited, yet 46% preferred a treatment plan focused on comfort and symptom management rather than life extension., Conclusion: Pakistani patients reported a need for better informed dialysis decision making and EoL care and better access to palliative care services. These findings underscore the need for palliative care training of Pakistani physicians and in other developing countries to help address communication and EoL needs of their dialysis patients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the fact that the transcription factor ATOH1 is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependent oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, which is one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression. Moreover, ATOH1 overexpression in these cells changed their growth characteristics from adherent to suspension and/orspheroidal growth, that is, resembling the neuroendocrine growth pattern of classical MCC cell lines. Notably, ectopic expression of different Merkel cell polyomavirus (MCPyV)-derived truncated large T antigens induced ATOH1 expression in fibroblasts, which was paralleled by miR-375 expression and similar morphologic changes. In summary, MCPyV-associated carcinogenesis is likely to induce the characteristic neuroendocrine features of MCC via induction of ATOH1; thus, ATOH1 can be regarded as a lineage-dependent oncogene in MCC., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An anatomic severity grade (ASG) score to categorize and to define anatomic factors for abdominal aortic aneurysm (AAA) repair was proposed. Other studies have previously reported that aortic anatomic complexity is a marker of survival and resource utilization after repair, although it remains unclear whether individual components of the ASG score independently contribute to survival. This study analyzed and validated an aortic and iliac artery calcium scoring system that can potentially predict survival after AAA repair., Methods: Patients who underwent infrarenal AAA repairs from July 2007 to May 2012 were analyzed using complete 5-year records. Those who died ≤30 days of surgery were excluded. Calcium score (CS) was defined using the ASG scoring system for its basis by preoperative imaging <6 months before surgery. A CS for any patient was 0 to 5 points, the sum of the points assigned to aortic neck (2 points total) and iliac artery (3 points total) calcification. A receiver operating characteristic curve was used to determine a CS threshold for mortality. The 5-year survivors and deaths were compared in regard to comorbidities, pharmacology, and CS at or above the defined threshold. Each variable with a P value <.1 between the groups was then placed into a Cox proportional hazards model, with statistical significance of P < .05., Results: There were 356 patients who underwent AAA repair with complete 5-year follow-up data; 26% died within 5 years of surgery. Of these, 13% had CS of 0 with 15% mortality, 28% had CS of 1 with 21% mortality, 24% had CS of 2 with 24% mortality, 23% had CS of 3 with 35% mortality, 10% had CS of 4 with 40% mortality, and 2% had CS of 5 with 17% mortality. The receiver operating characteristic curve demonstrated an appropriate threshold of CS 3. Of these patients, 65% had a CS <3, whereas 35% had a CS ≥3. Patients with a CS ≥3 had a lower 5-year survival probability (P = .003). Comparing 5-year survivors and deaths in a Cox proportional hazards analysis, CS ≥3 was associated with a hazard ratio of 1.579 (95% confidence interval, 1.038-2.402; P = .0328)., Conclusions: A CS ≥3 is linked to a lower 5-year survival after AAA repair in our population. This system potentially can be another measure for risk stratification and serve as a means to predict midterm mortality in AAA repairs. Future study will be needed for further validation to predict midterm mortality and to better guide surgical decision-making., (Published by Elsevier Inc.)

Objective: This study examined the relationship between two new variables, tumor distance to base of skull (DTBOS) and tumor volume, with complications of carotid body tumor (CBT) resection, including bleeding and cranial nerve injury., Methods: Patients who underwent CBT resection between 2004 and 2014 were studied using a standardized, multi-institutional database. Demographic, perioperative, and outcomes data were collected. CBT measurements were determined from computed tomography, magnetic resonance imaging, and ultrasound examination., Results: There were 356 CBTs resected in 332 patients (mean age, 51 years; 72% female); 32% were classified as Shamblin I, 43% as Shamblin II, and 23% as Shamblin III. The mean DTBOS was 3.3 cm (standard deviation [SD], 2.1; range, 0-10), and the mean tumor volume was 209.7 cm 3 (SD, 266.7; range, 1.1-1642.0 cm 3 ). The mean estimated blood loss (EBL) was 257 mL (SD, 426; range, 0-3500 mL). Twenty-four percent of patients had cranial nerve injuries. The most common cranial nerves injured were the hypoglossal (10%), vagus (11%), and superior laryngeal (5%) nerves. Both Shamblin grade and DTBOS were statistically significantly correlated with EBL of surgery and cranial nerve injuries, whereas tumor volume was statistically significantly correlated with EBL. The logistic model for predicting blood loss and cranial nerve injury with all three variables-Shamblin, DTBOS, and volume (R 2  = 0.171, 0.221, respectively)-was superior to a model with Shamblin alone (R 2  = 0.043, 0.091, respectively). After adjusting for Shamblin grade and volume, every 1-cm decrease in DTBOS was associated with 1.8 times increase in risk of >250 mL of blood loss (95% confidence interval, 1.25-2.55) and 1.5 times increased risk of cranial nerve injury (95% confidence interval, 1.19-1.92)., Conclusions: This large study of CBTs demonstrates the value of preoperatively determining tumor dimensions and how far the tumor is located from the base of the skull. DTBOS and tumor volume, when used in combination with the Shamblin grade, better predict bleeding and cranial nerve injury risk. Furthermore, surgical resection before expansion toward the base of the skull reduces complications as every 1-cm decrease in the distance to the skull base results in 1.8 times increase in >250 mL of blood loss and 1.5 times increased risk of cranial nerve injury., (Copyright © 2017. Published by Elsevier Inc.)

Background: Potential cost effectiveness of endovascular aneurysm repair (EVAR) compared with open aortic repair (OAR) is offset by the use of intraoperative adjuncts (components) or late reinterventions. Anatomic severity grade (ASG) can be used preoperatively to assess abdominal aortic aneurysms, and provide a quantitative measure of anatomic complexity. The hypothesis of this study is that ASG is directly related to the use of intraoperative adjuncts and cost of aortic repair., Methods: Patients who undergo elective OAR and EVAR for abdominal aortic aneurysms were identified over a consecutive 3-year period. ASG scores were calculated manually using three-dimensional reconstruction software by two blinded reviewers. Statistical analysis of cost data was performed using a log transformation. Regression analyses, with a continuous or dichotomous outcome, used a generalized estimating equations approach with the sandwich estimator, being robust with respect to deviations from model assumptions., Results: One hundred forty patients were identified for analysis, n = 33 OAR and n = 107 EVAR. The mean total cost (± standard deviation) for OAR was per thousand (k) $38.3 ± 49.3, length of stay (LOS) 13.5 ± 14.2 days, ASG score 18.13 ± 3.78; for EVAR, mean total cost was k $24.7 ± 13.0 (P = .016), LOS 3.0 ± 4.4 days (P = .012), ASG score 15.9 ± 4.13 (P = .010). In patients who underwent EVAR, 25.2% required intraoperative adjuncts, and analysis of this group revealed a mean total cost of k $31.5 ± 15.9, ASG score 18.48 ± 3.72, and LOS 3.9 ± 4.5, which were significantly greater compared with cases without adjunctive procedures. An ASG score of ≥15 correlated with an increased propensity for requirement of intraoperative adjuncts; odds ratio, 5.75 (95% confidence interval, 1.82-18.19). ASG >15 was also associated with chronic kidney disease, end stage renal disease, hypertension, female sex, increased cost, and use of adjunctive procedures., Conclusions: Complex aneurysm anatomy correlates with increased total cost and need for adjunctive procedures during EVAR. Preoperative assessment with ASG scores can delineate patients at greater risk for increased resource use. Patient comorbid factors are associated with anatomic complexity defined according to ASG. A critical examination of the relationship between anatomic complexity and finances is required within the context of aggressive endovascular treatment strategies and shifts toward value-based reimbursement., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the rate at which clinically normal eyes in unilateral keratoconus (KC) patients progress to KC and to identify the risk factors that might predict the development of KC in a longitudinal study., Design: Prospective observational study., Participants: We recruited 778 patients with KC and 252 normal controls in Los Angeles, California. One hundred sixteen of 778 patients (14.9%) were diagnosed with clinically unilateral KC at baseline., Methods: Both eyes of these unilateral KC patients were examined at baseline, and 85 patients were followed up with clinical evaluation and videokeratography for a period ranging from 6 months to 8 years., Main Outcome Measures: Progression to clinical KC from previously normal fellow eyes. Quantitative and qualitative videokeratography variables, contact lens wear, and demographic variables were analyzed as potential predictive factors for this progression., Results: During the follow-up period, 30 of 85 (35.3%) clinically normal fellow eyes had KC develop, and 25 of these 30 (83.3%) had KC develop within the first 6 years after the initial KC diagnosis. By use of the time period from the patients' first diagnosis of unilateral KC to the end of the follow-up period (range, 6 months-41 years), the median time (estimated from the survival analysis) to the development of KC was 16.7 years (95% confidence interval, 11.34, 28.91). Fellow eyes with higher inferior-superior dioptric asymmetry value (I-S) or KC percentage index (logKISA) values had higher risk for KC developing (I-S, risk ratio [RR] = 1.348, P = 0.022; log(KISA), RR = 4.245, P = 0.003). Asymmetric patterns also showed an increased risk for KC developing (P = 0.03), especially the asymmetric bowtie with skewed radial axes (AB/SRAX) pattern., Conclusions: Approximately 50% of clinically normal fellow eyes will progress to KC within 16 years. The greatest risk is during the first 6 years of the onset. Quantitative indices (I-S and KISA values) and qualitative patterns (AB/SRAX) might predict this progression.

The mechanism linking the APOE4 gene with increased susceptibility for Alzheimer's disease (AD) and poorer outcomes following closed head injury and stroke is unknown. One potential link is activation of the innate immune system in the CNS. Our previously published data demonstrated that apolipoprotein E regulates production of nitric oxide, a critical cytoactive factor released by immune active macrophages. To determine if immune regulation is different in the presence of apolipoprotein E4 compared to apolipoprotein E3, we have measured NO production by peritoneal and CNS macrophages (microglia) cultured from transgenic mice that only express the human apoE4 or apoE3 protein isoform. Significantly more NO was produced in APOE4 mice compared to APOE3 transgenic mice that only express human apoE3 protein. Similarly, monocyte derived macrophages from humans carrying APOE4 gene alleles also produce significantly greater NO than those individuals with APOE3. The mechanism for this isoform-specific difference in NO production is not known and multiple sites in the NO production pathway may be affected. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein are not significantly different between the APOE3 and APOE4 mice, suggesting that induction of iNOS is not a primary cause of the increased NO production in APOE4 animals. One alternative regulatory mechanism that demonstrates isoform specificity is arginine transport, which is greater in microglia from APOE4 transgenic mice compared to microglia from APOE3 mice. Increased transport is consistent with an increased production of NO and may reflect a direct or indirect effect of the APOE genotype on microglial arginine uptake and microglial activation in general. Overall, greater NO production in APOE4 carriers where characteristically high levels of oxidative/nitrosative stress are found in diseases such as AD provides a mechanism that potentially explains the genetic association between APOE4 and human diseases., (Copyright 2002 Elsevier Science Inc.)

Objective: The emerging role of transforming growth factor beta in hypertension, kidney disease, and trophoblast differentiation promoted our interest in evaluating the clinical value of assaying maternal serum TGF-beta2 levels in pregnancies complicated by preeclampsia and eclampsia. We wished to determine these levels in relation to the severity of the disease, the degree of renal involvement, and fetal outcome., Methods: A prospective study was carried out in 50 pregnant patients with preeclampsia (PE) and eclampsia and these women were compared to 20 pregnant normotensive controls. Preeclamptic patients were subdivided into 20 cases of mild PE, 20 cases of severe PE, and 10 cases of eclampsia. Maternal serum levels of TGF-beta2 were determined in all cases by enzyme immunoassay. Maternal serum creatinine and uric acid were measured, together with an assessment of fetal well being, using the Biophysical Profile Score., Results: Maternal serum TGF-beta2 levels were significantly increased in cases of severe preeclampsia and eclampsia compared to controls. This increase was positively correlated with elevated levels of serum creatinine and uric acid, as well as poor biophysical profile scores (BPS), and low birth weight (LBW)., Conclusion: Measurement of maternal serum TGF-beta2 levels in preeclampsia may be a useful biomarker for the assessment of the severity of disease and fetal outcome in PE.

Purpose: To determine the efficacy of simultaneous peripheral crescentic lamellar keratoplasty (LK) and central penetrating keratoplasty (PK) for advanced pellucid marginal degeneration (PMD)., Design: Retrospective, noncomparative, interventional case series., Participants: Five patients with advanced PMD., Method: Simultaneous peripheral crescentic LK and central PK followed by selective suture removal and astigmatic keratotomy in the postoperative period., Main Outcome Measures: These included interval of time required for visual rehabilitation, best spectacle-corrected visual acuity achieved, and amount of corneal astigmatism, as measured by videokeratography. Measuring the change in corneal astigmatism by videokeratography over the subsequent follow-up period after spectacle correction had been prescribed assessed stability of the achieved refraction., Results: Visual acuity results were 20/40 in three eyes, 20/80 in one eye, and 20/400 in one eye. The latter two had decreased acuity from posterior subcapsular cataract formation, which may have been caused by topical steroid use. The time required for visual rehabilitation ranged from 5.13 to 10.93 (mean, 9.92) months, and the amount of corneal astigmatism at the end of this period ranged from 0.3 diopters (D) to 5.3 D. A tendency for an increase in "with the rule astigmatism" after the rehabilitation period was noted. Two patients had elevations of intraocular pressure that responded to reduction in topical steroid dose., Conclusions: The short-term results with this technique are excellent in that it provides early and stable visual rehabilitation in patients with advanced PMD. Low to moderate levels of postkeratoplasty astigmatism were achieved in all the eyes treated. The usual tendency of an increase in "against the rule astigmatism" that occurs when PK alone is done for PMD was eliminated.