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Introduction: Surgical procedures in contemporary practice frequently employ energy-based devices, yet comprehensive education surrounding their safety and effectiveness remains deficient. We propose an innovative course for residents that aims to provide basic electrosurgery knowledge and promote the safe use of these devices. Methods: We developed a simulated training course for first-year general surgery and orthopedic residents. First, a survey was conducted regarding their knowledge perception about energy devices. The course consisted of two online theoretical sessions, followed by three in-person practical sessions. First-year residents performed three video-recorded attempts using a cadaveric model and were assessed through a digital platform using the Objective Structured Assessment of Technical Skill (OSATS), a Specific Rating Scale (SRS), and a surgical energy-based devices scale (SEBS). Third-year residents were recruited as a control group. Results: The study included 20 first-year residents and 5 third-year residents. First-year residents perceived a knowledge gap regarding energy devices. Regarding practical performance, both OSATS and checklist scores were statistically different between novices at their first attempt and the control group. When we analyzed the novice's performance, we found a significant increase in OSATS (13 vs 21), SRS (13 vs 17.5), and SEBS (5 vs 7) pre- and post-training scores. The amount of feedback referred to skin burns with the electro-scalpel reduced from 18 feedbacks in the first attempt to 2 in the third attempt (p-value = 0.0002). When comparing the final session of novices with the control group, no differences were found in the SRS (p = 0.22) or SEBS (p = 0.97), but differences remained in OSATS (p = 0.017). Conclusion: This study supports the implementation of structured education in electrosurgery among surgical trainees. By teaching first-year residents about electrosurgery, they can acquire a skill set equivalent to that of third-year residents. The integration of such courses can mitigate complications associated with energy device misuse, ultimately enhancing patient safety. [ABSTRACT FROM AUTHOR]

Forkhead box P3 (FOXP3) has been identified as a novel molecular marker in various types of cancer. The present study assessed the expression of FOXP3 in patients with head and neck squamous cell carcinoma (HNSCC) and its potential as a clinical prognostic indicator, and developed a radiomics model based on enhanced computed tomography (CT) imaging. Data from 483 patients with HNSCC were downloaded from the Cancer Genome Atlas for FOXP3 prognostic analysis and enhanced CT images from 139 patients included in the Cancer Imaging Archives, which were subjected to the maximum relevance and minimum redundancy and recursive feature elimination algorithms for radiomics feature extraction and processing. Logistic regression was used to build a model for predicting FOXP3 expression. A prognostic scoring system for radiomics score (RS), FOXP3, and patient clinicopathological factors was established to predict patient survival. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration curve and decision curve analysis (DCA) were used to evaluate model performance. Furthermore, the relationship between FOXP3 and the immune microenvironment, as well as the association between RS and immune checkpoint-related genes, was analyzed. Results of analysis revealed that patients with HNSCC and high FOXP3 mRNA expression exhibited better overall survival. Immune infiltration analysis revealed that FOXP3 had a positive correlation with CD4 + and CD8 + T cells and other immune cells. The 8 best radiomics features were selected to construct the radiomics model. In the FOXP3 expression prediction model, the AUC values were 0.707 and 0.702 for the training and validation sets, respectively. Additionally, the calibration curve and DCA demonstrated the positive diagnostic utility of the model. RS was correlated with immune checkpoint-related genes such as ICOS, CTLA4, and PDCD1. A predictive nomogram was established, the AUCs were 0.87, 0.787, and 0.801 at 12, 24, and 36 months, respectively, and DCA demonstrated the high clinical applicability of the nomogram. The enhanced CT radiomics model can predict expression of FOXP3 and prognosis in patients with HNSCC. As such, FOXP3 may be used as a novel prognostic marker to improve individualized clinical diagnosis and treatment decisions. [ABSTRACT FROM AUTHOR]

This study aimed to examine self-report of financial leverage, conflict, and satisfaction pertaining to representative payeeship for persons with mental illness, which research has not examined in the past decade. Sixty representative payee recipients with mental illness residing across the U.S. completed an online survey, with most (n = 50) receiving representative payeeship by family members/friends. Wilcoxon-Mann-Whitney tests and Spearman correlations were computed. One-third of participants reported experiencing financial leverage and conflict "sometimes" or more often and were dissatisfied with their representative payee arrangement. With the exception of use of alcohol and/or drugs, no participant characteristic was associated with financial leverage, conflict, or satisfaction. Financial leverage was reported to be greater when representative payees were family members/friends. Financial leverage and conflict were positively associated with each other and negatively associated with satisfaction. It is advisable that satisfaction with representative payeeship be increased and conflict resulting from representative payeeship be minimized. [ABSTRACT FROM AUTHOR]

Introduction: Blood pressure (BP) variability (BPV) has emerged as an indicator of subclinical organ damage and an independent predictor of cardiovascular disease (CVD) morbidity and mortality in high-risk populations. Aim: We aimed to assess short-term variability of both brachial and aortic BP in psoriasis, a common immune-mediated inflammatory disorder characterized by increased CVD risk. Methods: Psoriasis patients and non-psoriasis individuals had their BP assessed throughout a 24 h period (Mobil-O-Graph device). Brachial and aortic BPV during the 24 h and the respective daytime and nighttime periods was calculated from relevant ambulatory BP profiles. In-house software was applied to automatically calculate average real variability (ARV) of brachial and aortic systolic (bSBP, aSBP) and diastolic BP (bDPB, aDBP), and the weighted standard deviation (wSD) of 24 h bSBP/aSBP. 24 h pulse wave velocity (PWV) and augmentation index (AIx) were used as widely applied markers of arterial stiffness. Results: Psoriasis patients (n = 74) presented increased ARV of 24 h and daytime bSBP/aSBP, and increased ARV of 24 h and daytime bDBP/aDBP, compared to controls (n = 40). PWV and AIx correlated with ARV of 24 h bSBP/aSBP, daytime bSBP/aSBP, while PWV further correlated with ARV of nighttime aSBP. The observed associations with PWV, yet not AIx, with indices of BPV remained significant after adjusting for CVD risk factors. Conclusions: This is the first study reporting increased 24 h variability of both brachial and aortic BP in psoriasis. The association of short-term BPV with arterial stiffness implies a potential role of BPV in terms of CVD risk stratification in patients with chronic immune-mediated inflammation. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient's perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient's experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument. Methods: Data from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima's graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls. Results: EFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB). Discussion: Using two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated. Conclusions: This analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience. [ABSTRACT FROM AUTHOR]

Purpose: There have been no reports on the application of salivary iodine concentration (SIC) in evaluating iodine nutrition in pregnant women. This study aimed to clarify the relationship between SIC and indicators of iodine nutritional status and thyroid function during pregnancy, to investigate whether salivary iodine can be applied to the evaluation of iodine nutritional status in pregnant women, and to provide a reference basis for establishing a normal range of salivary iodine values during pregnancy. Methods: Pregnant women were enrolled in the Department of Obstetrics, the people's hospital of Yuncheng Country, Shandong Province, from July 2021 to December 2022, using random cluster sampling. Saliva, urine, and blood samples were collected from pregnant women to assess iodine nutritional status, and venous blood was collected to determine thyroid function. Results: A total of 609 pregnant women were included in this study. The median spot urinary iodine concentration (SUIC) was 261 μg/L. The median SIC was 297 μg/L. SIC was positively correlated with SUIC (r = 0.46, P < 0.0001), 24-h UIC (r = 0.30, P < 0.0001), 24-h urinary iodine excretion (24-h UIE) (r = 0.41, P < 0.0001), and estimated iodine intake (EII) (r = 0.52, P < 0.0001). After adjusting for confounders, there was a weak correlation between SIC and serum total iodine and serum non-protein-bound iodine (P = 0.02, P = 0.04, respectively). Pregnant women with a SIC < 176 μg/L had a higher risk of insufficient iodine status (OR = 2.07, 95% CI 1.35–3.19) and thyroid dysfunction (OR = 2.71, 95% CI 1.18–6.21) compared to those with higher SIC. Those having SIC > 529 μg/L were more likely to have excessive iodine status (OR = 2.82, 95% CI 1.81–4.38) and thyroid dysfunction (OR = 3.04, 95% CI 1.36–6.78) than those with lower SIC values. Conclusion: SIC is associated with urinary iodine concentration and thyroid function in pregnant women. SIC < 176 μg/L was associated with an increased risk for iodine deficiency and hypothyroxinemia, while SIC > 529 μg/L was related to excess and thyrotoxicosis. SIC can be used as a reference indicator for evaluating the iodine nutrition status of pregnant women, but it needs further investigation and verification. Trial registration: NCT04492657(Aug 9, 2022). [ABSTRACT FROM AUTHOR]

Autism is associated with genomic instability, which is regulated by telomere length (TL) and index of global methylation (LINE-1). This study will determine relative TL (RTL) and LINE-1 methylation percentage for 69 patients and 33 control subjects to evaluate their potential role as biomarkers for autism. The results displayed a significant decrease of both RTL and LINE-1 methylation in autistic cases relative to controls (P < 0.001). Analysis of receiver operating characteristics curve revealed that both of RTL and LINE-1 methylation percentage have the ability to serve as autism biomarkers (area under the curve = 0.817 and 0.889, respectively). The statistical analysis revealed positive correlation between the two biomarkers (correlation coefficient = 0.439 and P < 0.001). [ABSTRACT FROM AUTHOR]

Background: Video-assisted thoracoscopic surgery (VATS) often induces significant postoperative pain, potentially leading to chronic pain and decreased quality of life. This study aimed to evaluate the acetaminophen/ibuprofen combination effectiveness in reducing analgesic requirements and pain intensity in patients undergoing VATS. Study design: This is a double-blinded randomized controlled trial. Methods: Adult patients scheduled for elective VATS for lung resection were randomized to receive either intravenous acetaminophen and ibuprofen (intervention group) or 100 mL normal saline (control group). Treatments were administered post-anesthesia induction and every 6 h for three cycles. The primary outcome was total analgesic consumption at 24 h postoperatively. Secondary outcomes were cumulative analgesic consumption at 2 and 48 h; analgesic-related side effects at 2, 24, and 48 h; quality of recovery at 24 h and 48 h postoperatively; pain intensity at rest and during coughing; and rescue analgesics use. Chronic postsurgical pain (CPSP) was assessed through telephone interviews 3 months postoperatively. Results: The study included 96 participants. The intervention group showed significantly lower analgesic consumption at 24 h and 48 h postoperatively (24 h: median difference: − 100 µg equivalent intravenous fentanyl [95% confidence interval (CI) − 200 to − 5 μg], P = 0.037; 48 h: median difference: − 140 μg [95% CI − 320 to − 20 μg], P = 0.035). Compared to the controls, the intervention group exhibited a significantly lower quality of recovery 24 h post-surgery, with no significant difference at 48 h. All pain scores except for coughing at 48 h post-surgery were significantly lower in the intervention group compared to the controls. No significant differences were observed between the groups in postoperative nausea and vomiting occurrence, hospital stay length, and CPSP. Conclusion: Perioperative administration of acetaminophen/ibuprofen significantly decreased analgesic needs in patients undergoing VATS, providing an effective postoperative pain management strategy, and potentially minimizing the need for stronger analgesics. [ABSTRACT FROM AUTHOR]

The aim of the study is to examine the relationship between spiritual well-being, prenatal stress and attachment level of Turkish women conceiving spontaneously or with assisted reproductive techniques (ART). The comparative descriptive study type was conducted between November 2021 and June 2022 with 202 pregnant women, including 87 women conceiving with ART and 115 women conceiving spontaneously, who applied for routine prenatal care checkup in a state hospital in the west of Turkey. Both groups have a high level of spiritual well-being. Pregnant women in the ART group experience higher prenatal distress (9.6% for spontaneous, 12.6% for ART, p = 0.487) and low level of attachment (69.72 ± 7.98 for spontaneous, 66.24 ± 8.88 for ART, p = 0.006) compared to the other group. Additionally, as insufficient partner involvement in the prenatal process increases in pregnant women in both groups, prenatal attachment decreases. It is extremely important that midwives and nurses evaluate the spiritual well-being of pregnant women and provide holistic care in line with their spiritual needs. [ABSTRACT FROM AUTHOR]

Background: PET/CT is currently the gold standard for lung cancer staging, and it is also used to identify distant and nodal metastases. High-resolution MRI can also be used to diagnose and provide morphological details about lung cancer. Standardized uptake value 'SUV' calculated from PET/CT gives information about tumor behavior where the SUV reflects metabolic tumor activity. Apparent diffusion coefficient 'ADC' calculated from DW-MRI is a quantitative imaging marker aiming to assess tumor cellularity which reflects tumor behavior. The study aimed to correlate ADC assessed by DW-MRI and metabolic activity determined by SUV max in PET/CT in local and nodal staging of newly diagnosed NSCLC. Results: Our study involved twenty-one patients who were pathologically proven to be NSCLC, 19 males (90.5%) and 2 females (9.5%), with a median age of 61 years (ranging from 37 to 84 years). Among all NSCLC primary mass lesions, we observed a statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR (r = − 0.509 and p = 0.019, r = − 0.472 and p = 0.031 and r = − 0.434 and p = 0.049 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively). Additionally, we observed another statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR in NSCLC mediastinal lymph nodes (r = − 0.699 and p = 0.011, r = − 0.58 and p = 0.048 and r = − 0.629 and p = 0.028 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively). Conclusions: ADC values calculated from DW-MRI might act as a new prognostic tool owing to its significant inverse correlation with SUV max achieved from PET/CT in NSCLC primary mass lesions as well as mediastinal lymph nodes. [ABSTRACT FROM AUTHOR]

Purpose: Calcaneal fractures (CFs) are rare but potentially debilitating injuries. Apart from the open, far lateral or sinus tarsi approach, operative treatment can be performed minimally invasive and percutaneously with intramedullary nailing. In this study, we sought to investigate the functional outcome of severe CFs treated with the C-Nail® implant. Methods: Twenty-two CFs (9 × Sanders III and 8 × Sanders IV), operated between 2016 and 2019, were followed up with a mean duration of 36 (± 11) months. The AOFAS score, pre- and postoperative Böhler angles, wound healing disorders, and patient-reported outcome measures (PROMs) like pain levels and return to work/sport levels were assessed. Results: The mean AOFAS score was 72.0 (± 9.8). Four patients sustained wound healing disorders, yet no implant-associated surgical revision was required. Fifty percent of patients were pain-free within 1 year. Within 1 year, about 50% of the patients could return to sports, and about 80% of the patients could return to work. PROMs and functional results align with those from other implants reported in the literature. Conclusion: Intramedullary nailing of severe CFs with the C-Nail® implant can be considered a safe treatment alternative that yields acceptable results at mid-terms. [ABSTRACT FROM AUTHOR]

Background: The evidence on the relationship between adiposity and disease outcomes in paediatric Crohn's disease (CD) is limited and lacks consensus. Aim: To investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes. Design: Clinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m2) and high (≥25 kg/m2) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11–14 years) and post-puberty (15–17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables. Results: 848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = −0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001). Conclusions: A higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation. [ABSTRACT FROM AUTHOR]

Background: Revisional bariatric surgery after an index adjustable gastric band (AGB) may be indicated to remedy weight relapse or band-related complications. We examined outcomes five years following revision from AGB to laparoscopic sleeve gastrectomy (AGB-LSG) or to Roux-en-Y gastric bypass (AGB-RYGB). Methods: We conducted a retrospective review to identify patients (men and women, age 18–80) who underwent one revisional bariatric procedure with AGB as the index procedure at two medical centers in our healthcare system between January 2012 and February 2017. We only included patients with a pre-revision BMI > 30 kg/m2 for whom 5-year follow-up data were available. We compared 5-year weight loss and remission of comorbidities in patients undergoing AGB-LSG and AGB-RYGB conversion. Results: A total of 114 patients met inclusion criteria (65 AGB-LSG, 49 AGB-RYGB). At 5-year post-revision, percent total weight loss (3.4% vs 19.9%; p < 0.001), percent excess weight loss (7.0% vs 50.8%; p < 0.001) and decrease in BMI (1.5 vs 8.8; p < 0.001) was greater in AGB-RYGB vs. AGB-LSG. No significant difference in remission or development of new comorbidities was observed. Conclusion: Conversion of AGB to RYGB is associated with superior intermediate-term weight loss compared to conversion of AGB to LSG. Future multicenter studies with larger sample sizes are necessary to further describe the intermediate-term outcomes of revisional bariatric surgery. [ABSTRACT FROM AUTHOR]

Background: Hormonal doping in recreational sports is a public-health concern. The World Anti-Doping Agency (WADA) promoted the creation of the Athlete Biological Passport, aiming to monitor athlete's biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. We have determined in recreational bodybuilders the metabolic effects associated with different patterns of hormone abuse. All analyses were conducted using Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Chicago, IL). Results: We have assessed plasma concentrations of selected metabolic markers and fatty acid content in erythrocyte membranes of 92 male bodybuilders and in 45 healthy controls. Hormonal abuse was identified by anonymous questionnaires. 43% (%) of recruited bodybuilders regularly abused hormones, i.e., anabolic androgenic steroids (95%) often associated with GH (30%) and/or insulin (38%). HDL-cholesterol was lower in insulin and/or GH abusers. Alanine (ALT) and aspartic (AST) transaminases were greater in hormone abusing bodybuilders than in non-doping bodybuilders and controls. Insulin doping was selectively associated with increased plasma ALT-to-AST ratio. In erythrocyte membranes, elongase activity (i.e., stearic-to-palmitic ratio) was lower in insulin and/or growth hormone doping, whereas increased Δ-9 desaturase activity (i.e., palmitoleic-to-palmitic ratio) was selectively associated with insulin doping. Conclusions: In conclusion, our study demonstrates that insulin and GH abuse are characterized by multiple alterations of specific metabolic markers. Although further studies are needed to test whether longitudinal monitoring of selected metabolic marker such as muscle contraction time, HDL levels, ALT-AST ratio as well as the activities of selected enzymes (e.g. Δ-9 desaturase and elongase), could contribute to the detection of insulin and GH abuse in sport. Key Points: Drug abuse is common among bodybuilder athletes. Substances combinations can result in significant health risks, including cardiovascular events, hormonal imbalances, and metabolic complications. The World Anti-Doping Agency promoted the creation of the Athlete Biological Passport, aiming to monitor athlete's biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. The present study investigates the effects of insulin, GH, and AAS abuse on selected metabolic parameters of recreational bodybuilders to identify selective, sensitive markers useful in longitudinal doping detection and, possibly, to be incorporated in the WADA Athlete Biological Passport. [ABSTRACT FROM AUTHOR]

Background: Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. Objective: The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). Methods: CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥ 2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Results: Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Conclusions: Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. Trial Registration: ClinicalTrials.gov, NCT04040192, 31 July 2019. Plain Language Summary: Atopic dermatitis (AD) is an immuno-inflammatory skin disease that can last a long time. It causes skin lesions and intense itching. Topical AD treatments used reactively often fail to control the disease over a long period of time. Many are associated with safety concerns that limit long-term use. Crisaborole ointment is a nonsteroidal treatment for the skin and is used to treat mild-to-moderate AD. Previous studies showed that using crisaborole twice daily was effective and had few side effects in patients with mild-to-moderate AD. This study evaluated how effective and safe long-term treatment with once-daily crisaborole was compared with an ointment with no drug (vehicle). The study included patients aged ≥ 3 months with mild-to-moderate AD whose AD improved after previous treatment with twice-daily crisaborole. This study was designed to investigate how much crisaborole reduced the incidence of AD flares over 52 weeks in these patients. The study included 270 patients whose AD had improved after treatment with twice-daily crisaborole. Of these patients, 135 were randomly assigned to receive crisaborole once a day and 135 to receive vehicle once a day. Patients who received crisaborole had a significantly longer time before experiencing AD flares than those who received vehicle. Crisaborole was well tolerated, and no new or unexpected side effects were found when used as a once-daily maintenance treatment for 52 weeks. These results indicate that once-daily treatment with crisaborole could be a potential long-term maintenance treatment option in children and adults with mild-to-moderate AD. [ABSTRACT FROM AUTHOR]

The Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration (FDA) have been leaders in protecting and promoting the U.S. public health by helping to ensure that safe and effective drugs and biological products are available in the United States for those who need them. The null hypothesis significance testing approach, along with other considerations, is typically used to demonstrate the effectiveness of a drug or biological product. The Bayesian framework presents an alternative approach to demonstrate the effectiveness of a treatment. This article discusses the Bayesian framework for drug and biological product development, highlights key settings in which Bayesian approaches may be appropriate, and provides recent examples of the use of Bayesian approaches within CDER and CBER. [ABSTRACT FROM AUTHOR]

Purpose: The anterolateral distal tibial rim (anterior malleolus, AM) is frequently fractured in malleolar fractures. The aim of this study was to evaluate the medium-term outcomes of malleolar fractures involving the AM. Methods: Among 100 patients with AM fractures that were treated over a 10-year period, 50 patients were available for follow-up. Outcome was assessed with the Olerud Molander Ankle Score (OMAS), the Foot Function Index (FFI-D), the EuroQol (EQ)-5D-5L Index, the EQ-VAS and the AOFAS Ankle-Hindfoot Score. Type 1 AM fractures (bony syndesmotic avulsions) were fixed surgically with either a suture anchor or a transosseous suture in 11 of 22 cases (50%). Among type 2 AM fractures (with incisura and joint involvement), 68% were treated surgically with screw fixation. All three type 3 AM fractures (anterolateral tibial plafond impaction) were treated surgically with either screw or plate fixation. Results: At follow-up, the median OMAS was 75, the FFI-D 19, the EQ-5D-5L-Index 0.88, the EQ-VAS 70, and the AOFAS score 93. Assuming that the fracture severity increases from Supination–External Rotation to Pronation–External Rotation and Pronation–Abduction injuries, the AOFAS score (p < 0.001), OMAS score (p = 0.009), and FFI-D (p = 0.041) all showed a significantly inferior clinical outcome with increasing fracture severity. Patients who required surgical revision (n = 5) showed a significantly inferior outcome with the OMAS (p = 0.019). Conclusions: A differentiated treatment protocol tailored to dislocation, size, incisura involvement and joint impaction leads to favourable outcomes in complex malleolar fractures involving the AM. More data are needed on the outcome of AM fractures that are still commonly underestimated and overlooked. [ABSTRACT FROM AUTHOR]

The manual segmentation of muscles on magnetic resonance images is the gold standard procedure to reconstruct muscle volumes from medical imaging data and extract critical information for clinical and research purposes. (Semi)automatic methods have been proposed to expedite the otherwise lengthy process. These, however, rely on manual segmentations. Nonetheless, the repeatability of manual muscle volume segmentations performed on clinical MRI data has not been thoroughly assessed. When conducted, volumetric assessments often disregard the hip muscles. Therefore, one trained operator performed repeated manual segmentations (n = 3) of the iliopsoas (n = 34) and gluteus medius (n = 40) muscles on coronal T1-weighted MRI scans, acquired on 1.5 T scanners on a clinical population of patients elected for hip replacement surgery. Reconstructed muscle volumes were divided in sub-volumes and compared in terms of volume variance (normalized variance of volumes – nVV), shape (Jaccard Index—JI) and surface similarity (maximal Hausdorff distance—HD), to quantify intra-operator repeatability. One-way repeated measures ANOVA (or equivalent) tests with Bonferroni corrections for multiple comparisons were conducted to assess statistical significance. For both muscles, repeated manual segmentations were highly similar to one another (nVV: 2–6%, JI > 0.78, HD < 15 mm). However, shape and surface similarity were significantly lower when muscle extremities were included in the segmentations (e.g., iliopsoas: HD –12.06 to 14.42 mm, P < 0.05). Our findings show that the manual segmentation of hip muscle volumes on clinical MRI scans provides repeatable results over time. Nonetheless, extreme care should be taken in the segmentation of muscle extremities. [ABSTRACT FROM AUTHOR]

An inverse relationship between religiousness/spirituality (R/S) and psychometric intelligence (IQ) is well-documented in previous literature. However, the studies that have examined group differences on IQ regarding R/S have limited generalizability. The present study contributed to the literature by evaluating IQ among participants identifying as differentially religious/spiritual (i.e., religious only, spiritual only, both religious and spiritual, or neither religious nor spiritual) and among those classified as either Christian/Catholic, Atheist, or Agnostic. Four hundred and thirty-two participants (M age = 37.9; 36% men) participated online via Amazon's Mechanical Turk as part of a larger study and completed a brief measure of IQ, a scale of religiousness and spirituality, and a demographics questionnaire. Correlations between IQ and self-reported religiousness/spirituality were small and negative (Mean r = −0.17), consistent with previous literature. Multivariate analyses of covariance (MANCOVAs) controlling for age, gender, education, and socioeconomic status (operationalized by estimated annual household income) indicated that IQ scores tended to be lowest (p < 0.001) for "religious only" participants (estimated marginal mean [EMM] = 93.0) and highest for "neither religious nor spiritual" participants (EMM = 103.7). Furthermore, IQ scores were significantly lower (ps < 0.001) for Christian/Catholic participants (EMM = 96.7) compared to both Atheist (EMM = 104.9) and Agnostic participants (EMM = 107.5). Discussion of these findings, relationships to previous theoretical and empirical work, limitations of the present study, and directions for future inquiry are provided. [ABSTRACT FROM AUTHOR]

Research on the relationship between rainfall variability and conflicts has yielded contradictory results. This study is the first to show that the significance of the impact of rainfall variability on conflicts depends on the temporal unit of analysis. We prove this point by comparing the statistical significance of the linkages between georeferenced conflicts and rainfall variabilities at the monthly and annual levels with panel data analyses from 1989 to 2020. We find that a 10 percent increase in monthly rainfall decreases the risk of conflict incidence by 0.0298 percent, but annual rainfall variability is not statistically linked to conflict outbreaks. These statistically significant disparities result from the aggregation of data dispersion and the disregard for the timing of the impact of rainfall on conflicts. These findings highlight the importance of information on monthly rainfall variation when estimating the impact of rainfall on conflicts. [ABSTRACT FROM AUTHOR]

Purpose: Endotrophin is a newly discovered adipokine, and its clinical utility in diagnosing gestational diabetes mellitus (GDM) remains unclear. We aimed to investigate the possible association between endotrophin and GDM and determine its correlation with maternal metabolic parameters. Methods: Screening and diagnosis for GDM were carried out between the 24th and 28th weeks of gestation. The study included 50 patients with GDM and 37 healthy pregnant women. Endotrophin was assayed by a commercially available enzyme-linked immunosorbent assay kit. Results: The endotrophin level was significantly higher in the GDM group compared to uncomplicated pregnancies (121.98 ± 104.08 vs 72.5 ± 76.2, p < 0.05). Furthermore, the fasting glucose, fasting insulin, and HOMA-IR values of and plasma glucose levels obtained at 1 and 2 h after 75 g oral glucose administration were significantly higher in the GDM group than in the control group (p < 0.05). The Spearman analysis showed a statistically significant correlation between the endotrophin level and the fasting glucose, first-hour glucose, fasting insulin, HOMA-IR, and pre-pregnancy and current body mass indexes (BMI) in the GDM group (p < 0.05). Conclusion: Although oral glucose tolerance test (OGTT) is still the gold standard in the diagnosis of GDM, considering the technical difficulties and disadvantages of OGTT, endotrophin measurement at 24–28 weeks of pregnancy in healthy risk-free pregnant women seems to be an appropriate approach to limit the use of OGTT. [ABSTRACT FROM AUTHOR]

The latest data from the T2K and NO ν A experiments show a tension in their preferred values of the oscillation parameters. In this work, we try to identify the source of the tension between the data from these two experiments. An analysis of their data from various channels (individually, and combined) shows that the tension arises primarily from the ν e appearance data, and is compounded by the ν ¯ μ disappearance data. We provide an explanation for the tension based on parameter degeneracies. Apart from the analysis with the standard matter effect, we also analyse the data with the vacuum oscillation hypothesis. We find that vacuum oscillations fit the data as well as matter effects do; and also reduce the tension between the two experiments. We have also done a study of the future run of NO ν A, T2K and DUNE in the context of establishing this tension with higher statistical significance. [ABSTRACT FROM AUTHOR]

Summary: Background. Resistance to radiation therapy poses a major clinical problem for patients suffering from head and neck squamous cell carcinoma (HNSCC). Transforming growth factor ß (TGF-ß) has emerged as a potential target. This study aimed to investigate the radiosensitizing effect of galunisertib, a small molecule TGF-ß receptor kinase I inhibitor, on HNSCC cells in vitro. Methods. Three HNSCC cell lines were treated with galunisertib alone, or in combination with radiation. Of those three cell lines, one has a known inactivating mutation of the TGF-ß pathway (Cal27), one has a TGF-ß pathway deficiency (FaDu) and one has no known alteration (SCC-25). The effect on metabolic activity was evaluated by a resazurin-based reduction assay. Cell migration was evaluated by wound-healing assay, clonogenic survival by colony formation assay and cell cycle by FACS analysis. Results. Galunisertib reduced metabolic activity in FaDu, increased in SCC-25 and had no effect on CAL27. Migration was significantly reduced by galunisertib in all three cell lines and showed additive effects in combination with radiation in CAL27 and SCC-25. Colony-forming capabilities were reduced in SCC-25 by galunisertib and also showed an additive effect with adjuvant radiation treatment. Cell cycle analysis showed a reduction of cells in G1 phase in response to galunisertib treatment. Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF-ß signaling in combination with radiation. [ABSTRACT FROM AUTHOR]

Purpose: Fluid management is challenging in malaria patients given the risks associated with intravascular fluid depletion and iatrogenic fluid overload leading to pulmonary oedema. Given the limitations of the physical examination in guiding fluid therapy, we evaluated point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) and lungs as a novel tool to assess volume status and detect early oedema in malaria patients. Methods: To assess the correlation between IVC and lung ultrasound (LUS) indices and clinical signs of hypovolaemia and pulmonary oedema, respectively, concurrent clinical and sonographic examinations were performed in an observational study of 48 malaria patients and 62 healthy participants across age groups in Gabon. Results: IVC collapsibility index (CI) ≥ 50% on enrolment reflecting intravascular fluid depletion was associated with an increased number of clinical signs of hypovolaemia in severe and uncomplicated malaria. With exception of dry mucous membranes, IVC-CI correlated with most clinical signs of hypovolaemia, most notably sunken eyes (r = 0.35, p = 0.0001) and prolonged capillary refill (r = 0.35, p = 0.001). IVC-to-aorta ratio ≤ 0.8 was not associated with any clinical signs of hypovolaemia on enrolment. Among malaria patients, a B-pattern on enrolment reflecting interstitial fluid was associated with dyspnoea (p = 0.0003), crepitations and SpO2 ≤ 94% (both p < 0.0001), but not tachypnoea (p = 0.069). Severe malaria patients had increased IVC-CI (p < 0.0001) and more B-patterns (p = 0.004) on enrolment relative to uncomplicated malaria and controls. Conclusion: In malaria patients, POCUS of the IVC and lungs may improve the assessment of volume status and detect early oedema, which could help to manage fluids in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare outcomes between open (OR) and endovascular repair following superficial femoral artery (SFA) injuries. Methods: This is a cross-sectional study querying the 2012–2014 National Inpatient Sample for SFA injuries. Patients were grouped into OR and stent-graft placement (SGP). Primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay (HLOS), fasciotomy and amputation rate, and cost. Wilcoxon rank-sum, Kruskal–Wallis, Chi-squared test with Bonferroni adjustment were used as appropriate; p < 0.05 was significant. Results: 255 Patients were identified. Mean age was 34.6 years and majority were males. OR was performed in 82.7%. Overall mortality rate was 3.7%. Median HLOS was 8 days. Fasciotomies were performed in 31% and lower limb amputations in 3.7%. Males more often underwent OR (89.0% vs. 73.1%, p < 0.01). SGP patients were significantly older (44.9 vs. 32.5 years; p < 0.01), and with Medicare insurance (20.5% vs. 6.5%; p < 0.01. Mortality, HLOS, and hospitalization cost were not significantly different. OR patients had higher rate of fasciotomy (35.4% vs. 15.4%; p < 0.01). Conclusions: Endovascular management is not inferior to OR following SFA injuries and both carry a low amputation rate. OR is associated with a higher fasciotomy rate. Endovascular repair should be considered when technically feasible. [ABSTRACT FROM AUTHOR]

Background: Progression-free survival (PFS) is frequently used as a primary endpoint in late-phase clinical trials for anti-metastatic cancer agents. Previous studies have indicated that the frequency of tumor assessment affects the statistical power for PFS because progression dates are inaccurate; however, this finding may be difficult to generalize because of its unrealistic assumptions. Therefore, we re-examined this issue under realistic assumptions and various scenarios that approximate actual clinical trials. Methods: Randomized clinical trials comparing two interventions against a solid tumor were simulated under conditions where progressive disease (PD)-dominant PFS or a non-negligible number of deaths (death-competitive PFS) contributed to PFS events, which are conditions that resemble clinical trials of first-line therapy and later-line therapy, respectively. We assessed the impact of tumor assessment frequency on the statistical power. Results: Under the PD-dominant PFS condition, even in extreme scenarios, statistical power loss was only approximately 3%. Under the death-competitive PFS condition, tumor assessment frequency affected the statistical power of PFS if the effect of the treatment on overall survival was lower than that on time to progression. In this case, loss of statistical power was often more than 10% in some realistic scenarios. Conclusion: In trials investigating first-line treatments (PD-dominant PFS), tumor assessment frequency has a negligible impact on statistical power, whereas in trials investigating late-line therapies (death-competitive PFS), the potential impact of tumor assessment frequency on statistical power should be carefully evaluated at the design stage. [ABSTRACT FROM AUTHOR]

Community detection is a fundamental procedure in the analysis of network data. Despite decades of research, there is still no consensus on the definition of a community. To analytically test the realness of a candidate community in weighted networks, we present a general formulation from a significance testing perspective. In this new formulation, the edge-weight is modeled as a censored observation due to the noisy characteristics of real networks. In particular, the edge-weights of missing links are incorporated as well, which are specified to be zeros based on the assumption that they are truncated or unobserved. Thereafter, the community significance assessment issue is formulated as a two-sample test problem on censored data. More precisely, the Logrank test is employed to conduct the significance testing on two sets of augmented edge-weights: internal weight set and external weight set. The presented approach is evaluated on both weighted networks and un-weighted networks. The experimental results show that our method can outperform prior widely used evaluation metrics on the task of individual community validation. [ABSTRACT FROM AUTHOR]

Purpose: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. Methods: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. Results: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. Conclusion: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs. [ABSTRACT FROM AUTHOR]