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Belzutifan (Welireg, Merck & Co., Inc., Rahway, NJ, USA) is an oral, potent hypoxia‐inducible factor‐2α inhibitor, recently approved in the United States for the treatment of von Hippel–Lindau (VHL) disease‐associated renal cell carcinoma (RCC) and other VHL disease‐associated neoplasms. Safety and efficacy were investigated in two clinical studies: a Phase 1 dose escalation/expansion study in solid tumors and RCC and a Phase 2 study in VHL‐RCC. A population pharmacokinetic model was used to estimate belzutifan exposures to facilitate exposure–response (E‐R) analyses for efficacy and safety endpoints. Relationships between exposure and efficacy (overall response rate, disease control rate, progression‐free survival, best overall tumor size response, and other endpoints), safety outcomes (Grade ≥3 anemia, Grade ≥3 hypoxia, and time to first dose reduction/dose interruption), and pharmacodynamic biomarkers (erythropoietin [EPO] and hemoglobin [Hgb]) were evaluated using various regression techniques and time‐to‐event analyses. Efficacy E‐R was generally flat with non‐significant positive trends with exposure. The safety E‐R analyses demonstrated a lack of relationship for Grade ≥3 hypoxia and a positive relationship for Grade ≥3 anemia, with incidences also significantly dependent on baseline Hgb. Exposure‐dependent reductions in EPO and Hgb were observed. Based on the cumulative benefit–risk assessment in VHL disease‐associated neoplasms using E‐R, no a priori dose adjustment is recommended for any subpopulation. These analyses supported the benefit–risk profile of belzutifan 120 mg once daily dosing in patients with VHL‐RCC for labeling and the overall development program. [ABSTRACT FROM AUTHOR]

Aims: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance. [ABSTRACT FROM AUTHOR]

This article examines the real-world use and effectiveness of baricitinib, a small molecule inhibitor, for the treatment of moderate-to-severe atopic dermatitis (AD). The study, conducted in the TREATgermany registry with over 1600 patients, found that a majority of patients had previously tried other systemic therapies before using baricitinib. The results showed that after 3 months of treatment, there was a positive response in terms of disease severity, and the treatment was well-tolerated. The study was supported by various pharmaceutical companies, and the authors acknowledge the contributions of patients, physicians, clinical staff, and the TREATgermany Study Group. [Extracted from the article]

Objective: To explore the usefulness of the 'differential renal length index' (iDRL) before and after pyeloplasty, as the anteroposterior diameter is commonly used to quantify hydronephrosis but inaccuracies arise due to interobserver variability, hydration status and pure intra‐renal dilatation. Patients and Methods: Prospectively collected data, from two centres, of all children undergoing pyeloplasty for isolated unilateral pelvi‐ureteric junction obstruction (PUJO) (2015–2021) were analysed. Subgroup analysis was undertaken: Group A – differential renal function (DRF) ≥40%, Group B – subnormal DRF (20–39%), and Group C – symptomatic. Children with structural anomalies of upper and lower urinary tract, bilateral involvement, and subnormal DRF (<20%) were excluded. All the children had a pre‐ and postoperative ultrasound scan and Tc99m mercapto‐acetyltriglycine (MAG3) renograms. The iDRL was calculated as follows: iDRL = ([a – b]/b) × 100, where 'a' is the length of hydronephrotic kidney (cm) and 'b' is the length of contralateral normal kidney (cm). The mean difference and standard error of mean (SEM) between the pre‐ and postoperative iDRL was evaluated using the paired Student's t‐test, with P < 0.05 considered statistically significant. Results: A total of 119 children with 1‐year follow‐up were included. For the entire cohort, the mean (SEM) preoperative iDRL was 27.7 (1.4) and postoperatively was 12.5 (1.1), with a mean (range) DRF improvement of 54% (44–66%) (P < 0.001). In Group A (n = 97), the mean (SEM) preoperative iDRL was 26.6 (1.5) and postoperatively was 13.1 (1.2), with a mean (range) DRF improvement of 50% (38–63%) (P < 0.001). In Group B (n = 22), the mean (SEM) preoperative iDRL was 32.6 (3.5) and postoperatively was 10.0 (2.8), with a mean (range) DRF improvement of 69% (49–89%) (P < 0.001). In Group C (n = 28), the mean (SEM) preoperative iDRL was 19.9 (2.3) and postoperatively was 7.7 (1.9), with a mean (range) DRF improvement of 61% (38–85%) (P < 0.001). Conclusion: Our study identifies the iDRL as a useful measure of improvement following successful pyeloplasty. In the subgroup with DRF of >39% minimum improvement was >37%. Similar minimum DRF improvement was also noted (>37%) in hypo‐functioning kidneys and symptomatic PUJO. [ABSTRACT FROM AUTHOR]

Global challenges, such as the COVID‐19 impacts, climate crisis, and geopolitical tensions, have prompted economic transformations. These issues have led to macroeconomic data assuming non‐normal distributions, necessitating a nonlinear analytical approach. As a result, this study unveils the influence of energy intensity, renewable energy, economic growth, and financial development on carbon dioxide emissions in Iceland from 1995Q1 to 2020Q4 using the Quantile‐on‐Quantile Kernel‐Based Regularized Least Squares (QQKRLS) and Wavelets Quantile Correlation (WQC) methods. The QQKRLS results showed that energy intensity, renewable energy, and economic growth are negatively associated with carbon dioxide emissions across various quantiles, while financial development is positively linked with carbon dioxide emissions. Furthermore, the WQC outcomes confirm the results of the QQKRLS. In addition, in the short and medium term, financial development negatively affects carbon dioxide emissions across various quantiles, while in the long term, financial development positively influences carbon dioxide emissions. In light of the results gleaned from this study, Iceland should continue on its path of renewable energy investments, create policies that will completely decouple economic growth from carbon dioxide emissions, and ensure that the development of the financial system is funding clean energy activities. This provides a roadmap for sustainable economic and environmental development. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to explore the possibility to perform an asymmetric reduction, utilising a CBS‐type catalyst, of prochiral aryl methyl ketones under electrochemical conditions to generate the needed BH3 upon oxidation of NaBH4 with in situ generated I2 in the anode compartment. Therefore, various electrochemical parameters were optimised to conduct the desired formation of the chiral secondary alcohols in high to quantitative yields with a high stereochemical induction, although the catalyst loading had to be chosen relatively high to concur with the racemic reduction of the ketones by the electrogenerated BH3. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a rarely reported arrhythmia in otherwise healthy newborn foals, with a single case of cardioversion using procainamide administration described in the literature. Two neonatal Thoroughbred colts were presented to an equine hospital because of an irregularly irregular tachyarrhythmia and poor latching when trying to nurse. History, physical examination, and initial diagnostic testing including ECG and echocardiography confirmed AF without structural heart disease. The 1st foal converted into normal sinus rhythm after treatment with IV metoprolol and quinidine. The 2nd foal converted to normal sinus rhythm after a single IV dose of metoprolol, intended for rate control. Demeanor and nursing behavior improved markedly after conversion. The 2 foals had normal heart rates and sinus rhythm that persisted for 6 weeks until euthanasia in the 1st foal and for 2 years in the 2nd foal. Rate control and cardioversion should be considered as a treatment for persistent lone AF in neonatal foals. [ABSTRACT FROM AUTHOR]

Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia‐reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N‐acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90‐minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N‐acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P <.05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric‐reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P <.001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy. [ABSTRACT FROM AUTHOR]

The quest for augmenting dropwise condensation heat transfer performance has been the driving force behind the exploration of innovative techniques and approaches to fulfill the desired objective. Mostly, earlier research on dropwise condensation was devoted to study condensation from horizontal tubes and plates but, rarely, addressed dropwise condensation from vertical tubes. An interesting topic of current research in dropwise condensation is to explore the application of Slippery Liquid Infused Porous Surfaces (SLIPSs) to improve the condensation performance. The aforesaid facts are the motivation behind the topics of interest in the present study. In this study, we explore the applicability of semisolid lubricant‐impregnated porous surfaces in enhancing dropwise condensation performance of a vertical condenser tube. The experiments conducted over a wide range of subcooling (5°C ≤ ΔT ≤ 65°C) in saturated steam environment showed significant improvement in condensation heat transfer coefficient of a vertical condenser tube impregnated with semisolid lubricants when compared to bare vertical condenser tube. The highest enhancement is found to be 280% at a subcooling of 40°C. Furthermore, these surfaces proficiently sustain dropwise condensation over a period of 72 hours without compromising heat transfer performance. The devised fabrication method is simpler, more cost‐effective, and less time‐consuming than earlier techniques used for creating SLIPSs. Additionally, an approach based on numerical optimization by a stochastic global optimization technique, namely, Genetic Algorithm, is proposed to retrieve the coefficients and the exponent in the mathematical expression of overall resistance, that is being used to compute the tube‐side dropwise convection heat transfer coefficient. [ABSTRACT FROM AUTHOR]

Cannabis‐infused foods are currently on the rise in markets all around the world. Meanwhile, there are concerns over the health implications for consumers. Studies have explored the therapeutic potential and nutritional and economic benefits of cannabis usage. Yet, the phytonutrients, processing methods, and health implications of cannabis‐infused foods have not been well explored. This review evaluates existing evidence on the nutritional, processing, safety, and phytonutrient composition of cannabis‐infused food products and their medicinal and functional prospects. Cannabis seeds contain the highest amount of dietary nutrients, while flowers contain the highest amount of bioactive constituents. Oils, butter, seeds, flowers, and leaf extracts are the plant forms currently incorporated into food products such as beverages, baked products, cooking ingredients, functional foods, nutraceuticals, and nootropics. Cannabis‐infused foods have been found to offer therapeutic benefits for pain management, brain function, gut health, and certain cancers. Findings also show significant constraints associated with cannabis‐infused foods regarding dosage guidelines, limited research, efficacy, and long‐term health effects on consumers. This is further worsened by the lack of policies that regulate the industry. To realize the full potential of cannabis use in the food and health industries and in research, regulatory guidelines are needed to control dosages and improve its efficient use in these industries. This will go a long way to ensure the safety of cannabis users and enhance responsible production, marketing, and distribution. [ABSTRACT FROM AUTHOR]

The role of runoff in providing nutrients to runon loci in deserts was not extensively explored. Here we report 2 years of measurements of the chemical composition of rain and runoff (three events for each year, which correspond to the long‐term runoff events) in plots that were constructed over four biocrust types in the Negev Desert, Israel. The enrichment ratios showed high variability, being high for K+ (3.7), moderately high for NH4+ (1.6) and slightly high for Mg2+ and SO42− (1.2). It was low for Cl− and NO3− (0.5), moderately lower for Ca2+ (0.7) and slightly lower for Na+ and HCO3− (0.8). When examined per rain event, significant higher concentrations were found for K+ and Mg2+ while NO3− exhibited significantly lower concentration. The high enrichment of K+ and the enrichment of Mg2+ may point to a biogenic origin. While K+ enrichment is suggested to result from K+ excretion by the cyanobacteria, bacteria, and possibly by the mosses following cell wetting and the K+ role in cell osmoregulation, decomposition and erosion of the chlorophyll pigment may result in Mg2+ release. On the other hand, the data point out that despite the crust capability to fix nitrogen and thus to provide its own needs for nitrogen, NO3− was depleted from the runoff water, a phenomena that may be explained by the crust preference to utilise available low‐cost nitrogen provided by rain. Due to runoff accumulation at small depressions within the interdune and at the dune‐interdune interface, runoff may contribute additional amount of nutrients to these habitats. For the dune‐interdune interface it may account for an addition of 273.8% and 35.3% of the total potassium and nitrogen, respectively. The addition of water and nutrients may have important contribution to the growth of the moss‐dominated biocrusts and the shrubs at the dune‐interdune interface, being responsible for the formation of 'mantles and islands of fertility' at the dune‐interdune interface. It also points to the possible role that biocrusts may play in agroforestry practices. [ABSTRACT FROM AUTHOR]

Introduction: Simultaneous pancreas–kidney transplantation (SPK) is the preferred treatment for individuals with type‐1 diabetes and end‐stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. Methods: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain‐dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg. Results: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re‐exploration. During a 5–27‐month follow‐up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%–5.2%), with 100% graft and patient survival. Conclusion: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk–benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates. [ABSTRACT FROM AUTHOR]

Among phytophagous insects, life history often evolves as a strategy to cope with seasonality in host plant availability. Whereas specialization often leads to dormancy, aestivation, or longevity, polyphagous species bridge between periods of host availability by exploiting alternative host plants. The aim of the present work was to characterize the life histories of four species of specialist and generalist uni‐ and multivoltine frugivorous fruit flies – Ceratitis capitata Wiedemann, Anastrepha fraterculus Wiedemann, Rhagoletis blanchardi Aczel, and Rhagoletotrypeta pastranai Aczel (all Diptera: Tephritidae) – inhabiting in sympatry in Las Yungas phytogeographical province in Tucumán (northwestern Argentina). For this purpose, infested host plant fruits were sequentially collected during two consecutive years, and flies recovered from these fruits were subjected to demographic experiments to establish longevity and overwintering mechanisms. The results indicated that life cycles were tightly related to host fruit availability, where multivoltine species sequentially exploit different host plants over the year, whereas univoltine species must undergo pupal dormancy to reach the next host fructification period and may extend the duration of dormancy when climatic conditions are acyclic and unpredictable. The present study may broaden knowledge about diapausing Tephritidae in subtropical regions and may contribute to an increased conceptual basis for the improvement of pest control strategies, such as the sterile insect technique (SIT). [ABSTRACT FROM AUTHOR]

Hawassa is a rapidly developing city in Lake Hawassa watershed of Ethiopia. Analyzing the effect of land cover dynamics on surface runoff remains imperative to adaptive urban stormwater management. This study quantified spatial variation of land cover and sensitivity of stormwater management response. Historical 30 years of daily annual rainfall, three satellite imageries, DEM, and hydrological soil group data were analyzed. A statistical‐based combined approach of geospatial techniques and Soil Conservation Service‐Curve Number (SCS‐CN) model was employed. CN and surface runoff depth for the delineated urban watersheds were determined. The result revealed that the built‐up area increased by 30.9 km2, where the rate varies spatially. The variation of impervious land cover explains 58.6% of change in CN with coefficient of 0.352. While CN is inversely correlated with agricultural and vegetation land cover variations. The finding suggests CN explains 96.78% of the change in surface runoff with a significant correlation coefficient of 3.91. The proposed integrated model approach justifies the potential to reorganize the relationship between the spatial effect of land cover variation on surface runoff at the urban watersheds. Thus, suitable local‐specific solutions can be devised for effective management of flood risk and optimize the drainage system of urban areas. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to understand the effect of time to remission of acromegaly on survival in people living with acromegaly. Design, Patients and Measurement: This cross‐sectional study used data from the UK Acromegaly Register. We considered remission of acromegaly growth hormone controlled at ≤2 μg/L following the diagnosis of acromegaly. We used the accelerated failure time model to assess the effect of time to remission on survival in acromegaly. Results: The study population comprises 3569 individuals with acromegaly, with a median age of diagnosis of 47.3 (36.5–57.8) years, 48% females and a majority white population (61%). The number of individuals with the first remission of acromegaly was 2472, and the median time to first remission was 1.92 (0.70–6.58) years. In this study, time to first remission in acromegaly was found to have a significant effect on survival (p <.001); for every 1‐year increase in time to first remission, there was a median 1% reduction in survival in acromegaly. In an analysis adjusted for covariates, the survival rate was 52% higher (p <.001) in those who underwent surgery as compared to those who did not have surgery, 18% higher (p =.01) in those who received treatment with somatostatin analogues (SMA) as compared to those with dopamine agonists and 21% lower (p <.001) in those who received conventional radiotherapy as compared to those who did not receive radiotherapy. Conclusion: In conclusion, this population‐based study conducted in patients with acromegaly revealed that faster remission time, surgical intervention and treatment with SMA are linked to improved survival outcomes. [ABSTRACT FROM AUTHOR]

An efficient strategy has been developed for the synthesis of 3‐substituted lawsones using a catalytic amount of Sc(OTf)3 in toluene at −78 °C through a Buchner‐Curtius‐Schlotterbeck reaction. It is a versatile method to produce a large number of 3‐aryl, 3‐styryl, 3‐alkyl, and 3‐heteroaryl substituted lawsones under mild conditions. This is a first report on the synthesis of 3‐substituted lawsones in high yields with in short reaction times. [ABSTRACT FROM AUTHOR]

Verbal working memory (vWM) is an essential limited‐capacity cognitive system that spans the fronto‐parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high‐definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high‐density magnetoencephalography (MEG). Significant neural responses at the sensor‐level were imaged using a beamformer and whole‐brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD‐tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion The single simple question (SSQ), “What percentage of normal (0%–100%) do you feel regarding your disease?” has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes.A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch‐built Overall Disability Scale (RODS).The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = −.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%–70%, and 34% with SSQ >70%).The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length‐dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP. [ABSTRACT FROM AUTHOR]

Sustainable growth and the reduction of environmental pressures are important priorities that are issues of concern for both developed and developing countries. However, while carbon emissions and ecological footprint are commonly used by researchers in the context of environmental deterioration, a broader and more extensive metric for ecological quality is considered necessary. From this perspective, the load capacity factor provides a more detailed sustainable environment appraisal by simultaneously considering biocapacity and ecological footprint. Limited studies have examined the determinants of load capacity factor (LCAP). This survey attempts to fill the gap, using the case of Japan. Employing the dynamic ARDL approaches, the present research investigates the effect of renewable energy usage, economic growth, economic complexity, financial development, and trade globalization on load capacity factor in Japan for the period between 1980 and 2017. The empirical evidence indicates that economic complexity, economic growth, and financial development adversely impact LCAP, whereas renewable energy usage and trade globalization positively affect LCAP. Hence, we recommend that it is essential for Japan to attain self‐sufficiency in essential goods and minimize its reliance on the rest of the world. Furthermore, policymakers should capitalize on the benefits of trade globalization by adopting additional measures aimed at facilitating trade liberalization. [ABSTRACT FROM AUTHOR]

Objective: To understand US hospitals' initial strategic responses to the federal price transparency rule that took effect January 2021. Data Sources and Study Setting: Primary interview data collected from 12 not‐for‐profit hospital organizations in six US metropolitan markets. All but one organization were multihospital systems; the 12 organizations represent a total of 81 hospitals. Study Design: Exploratory, cross‐sectional, qualitative interview study of a convenience sample of hospital organizations across six geographically and compliance diverse markets. Data Collection/Extraction Methods: In‐depth, semi‐structured, qualitative interviews with 16 key informants across sampled organizations between November 2021 and March 2022. Interviews solicited data about internal organizational factors and external market factors affecting strategic responses. Transcribed interviews were de‐identified, coded, and analyzed using the constant comparative method. Principal Findings: Hospitals' strategic responses were influenced internally by the degree of the regulation's alignment with organizational values and goals, and task complexity vis‐a‐vis available resources. We found extensive variation in organizational capabilities to comply, and all but one organization relied on consultants and vendors to some degree. Key external factors driving strategic responses were hospitals' variable perceptions about how available price information would affect their competitive position, bottom line, and reputation. Organizations with more confidence in their interpretation of the environment, including how peers or purchasers would behave, and greater clarity in their own organization's position and goals, had more definitive initial strategic responses. In the first year, organizations' strategic responses skewed toward compliance, especially for the rule's consumer shopping requirements. Conclusions: A deeper understanding of the realities of operationalizing price transparency policy for hospitals is needed to improve its impact. [ABSTRACT FROM AUTHOR]

Background: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long‐term outcomes of PTLD following pancreas transplantation at a single center. Methods: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas–kidney transplants (SPK), and pancreas after kidney transplants (PAK). Results: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30‐year incidence of PTLD did not differ by transplant type—7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein‐Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD‐specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). Conclusions: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV‐negative recipients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ptosis associated with rhinosinusitis may indicate orbital or cavernous sinus involvement, typically accompanied by various other symptoms. However, isolated ptosis is a rare occurrence. This explains the diverse treatment approaches found in this literature review, ranging from conservative management to surgery. Imaging plays a crucial role in diagnosis and treatment planning. Isolated upper lid ptosis is a rare manifestation of acute rhinosinusitis, typically occurring without other neuro‐ophthalmological or orbital signs. This report presents a case of unilateral isolated ptosis in an adult male with acute rhinosinusitis. A 30‐year‐old male with asthma and bipolar disorder, and recent intranasal drug use, presented with nasal congestion, facial pressure, headache, and left eye droopiness. Neurological examination found left ptosis as the only abnormality. Lab results were normal, and COVID‐19 PCR was negative. Imaging showed pansinusitis without complications. The patient received IV antibiotics and steroids, followed by oral antibiotics and steroids. Ptosis resolved within 3 days and did not recur at three‐month follow‐up. Only seven cases of isolated ptosis with rhinosinusitis have been reported, all in males, most recovering with medical therapy alone. This is the first case treated with high‐dose steroids in addition to antibiotics. Isolated ptosis may be due to inflammation of the oculomotor nerve's distal branch or related muscular structures. Isolated ptosis in rhinosinusitis has a favorable prognosis. Imaging is crucial to exclude severe complications. The role of steroids needs further evaluation, and the timing for considering surgery remains to be defined. [ABSTRACT FROM AUTHOR]

Background: Many instructors transitioned their courses from face‐to‐face environments to computer‐mediated learning environments (CMLEs) following the onset of the coronavirus disease 2019 (COVID‐19) pandemic. However, little was known about how teleconferencing platforms and their corresponding functions affect student learning when the COVID‐19 pandemic began. Objectives: The aim of this study was to provide more clarity on the conditions through which online teleconferencing platforms influence student achievement. More specifically, this study investigated how displaying lecture‐relevant and lecture‐irrelevant messages in a chat box during a video lecture delivered via the Zoom teleconferencing platform affected student learning and note taking. Methods: Participants viewed the video lecture either with (relevant or irrelevant) or without messages appearing in the chat box of the Zoom window. Participants completed a learning test immediately following the lecture. Results and Conclusions: No difference regarding student achievement was observed between the three groups. However, results revealed that students in the relevant‐lecture messages group reported a higher extraneous cognitive load than the other groups even if they reported positive attitudes about the messages appearing on the chat box. Students in the lecture‐relevant group also recorded more notes during the lecture compared to the two other groups, but this result did not reach significance. This study extends previous research that investigated how messaging influences learning in classroom settings. Findings suggest that allowing relevant discussions is not the best strategy to promote learning in CMLEs as this information seems to compete with the other relevant information being presented during the ongoing lecture. Lay Description: What is already known about this topic: In video lectures, the chat box has been identified as the function most often used to support students' learning.Responding to lecture‐relevant messages can enhance students' learning.However, it remains unknown how simply reading, but not responding to, lecture‐relevant and lecture‐irrelevant messages can affect learning and note taking. What this paper adds: In previous studies, researchers examined how messaging affects learning in a classroom setting, but not within a computer‐mediated lecture environment.The present study extends previous research that investigated how messaging influences learning in classroom settings.This study provides more clarity on the conditions through which online teleconferencing platforms affect student learning and note taking.Findings suggest that allowing relevant discussions is not the best strategy to promote learning in CMLEs as this information seems to compete with the other relevant information being presented during the ongoing lecture. Implications for practitioners: The features of video lectures are critical factors, as they influence students' learning and should therefore be taken into account when designing educational materials.Instructors should not allow students to engage in lecture‐relevant and irrelevant messaging and discussion during video lectures as it competes with the other relevant information being presented. [ABSTRACT FROM AUTHOR]

Background: The American Academy of Physical Medicine and Rehabilitation (AAPM&R) conducted a comprehensive review in 2021 to identify opportunities for enhancing the care of adult and pediatric patients with spasticity. A technical expert panel (TEP) was convened to develop consensus‐based practice recommendations aimed at addressing gaps in spasticity care. Objective: To develop consensus‐based practice recommendations to identify and address gaps in spasticity care. Methods: The Spasticity TEP engaged in a 16‐month virtual meeting process, focusing on formulating search terms, refining research questions, and conducting a structured evidence review. Evidence quality was assessed by the AAPM&R Evidence, Quality and Performance Committee (EQPC), and a modified Delphi process was employed to achieve consensus on recommendation statements and evidence grading. The Strength of Recommendation Taxonomy (SORT) guided the rating of individual studies and the strength of recommendations. Results: The TEP approved five recommendations for spasticity management and five best practices for assessment and management, with one recommendation unable to be graded due to evidence limitations. Best practices were defined as widely accepted components of care, while recommendations required structured evidence reviews and grading. The consensus guidance statement represents current best practices and evidence‐based treatment options, intended for use by PM&R physicians caring for patients with spasticity. Conclusion: This consensus guidance provides clinicians with practical recommendations for spasticity assessment and management based on the best available evidence and expert opinion. Clinical judgment should be exercised, and recommendations tailored to individual patient needs, preferences, and risk profiles. The accompanying table summarizes the best practice recommendations for spasticity assessment and management, reflecting principles with little controversy in care delivery. [ABSTRACT FROM AUTHOR]

Delay discounting refers to the behavioral tendency to devalue rewards as a function of their delay in receipt. Heightened delay discounting has been associated with substance use disorders and multiple co‐occurring psychopathologies. Human and animal genetic studies have established that delay discounting is heritable, but only a few associated genes have been identified. We aimed to identify novel genetic loci associated with delay discounting through a genome‐wide association study (GWAS) using Heterogeneous Stock (HS) rats, a genetically diverse outbred population derived from eight inbred founder strains. We assessed delay discounting in 650 male and female HS rats using an adjusting amount procedure in which rats chose between smaller immediate sucrose rewards or a larger reward at various delays. Preference switch points were calculated and both exponential and hyperbolic functions were fitted to these indifference points. Area under the curve (AUC) and the discounting parameter k of both functions were used as delay discounting measures. GWAS for AUC, exponential k, and one indifference point identified significant loci on chromosomes 20 and 14. The gene Slc35f1, which encodes a member of the solute carrier family, was the sole gene within the chromosome 20 locus. That locus also contained an eQTL for Slc35f1, suggesting that heritable differences in the expression might be responsible for the association with behavior. Adgrl3, which encodes a latrophilin subfamily G‐protein coupled receptor, was the sole gene within the chromosome 14 locus. These findings implicate novel genes in delay discounting and highlight the need for further exploration. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic intestinal failure (CIF) are at increased risk of developing renal impairment. The aim of this study was to evaluate the occurrence of chronic kidney disease (CKD) in patients dependent on home parenteral nutrition (HPN) and assess risk factors for renal impairment, including patients with all mechanisms of CIF. Methods: This was a cohort study of patients initiated on HPN between March 1, 2015, and March 1, 2020, at a national UK IF Reference Centre. Patients were followed from their first discharge with HPN until HPN cessation or the end of follow‐up on December 31, 2021. Results: There were 357 patients included in the analysis. Median follow‐up time was 4.7 years. At baseline, >40% of patients had renal impairment, with 15.4% fulfilling the criteria for CKD. Mean estimated glomerular filtration rate (eGFR) decreased significantly during the first year after initiation of HPN from 93.32 ml/min/1.73 m2 to 86.30 ml/min/1.73 m2 at the first year of follow‐up (P = 0.002), with sequential stabilization of renal function. Increased age at HPN initiation and renal impairment at baseline were associated with decreased eGFR. By the end of follow‐up, 6.7% patients developed renal calculi and 26.1% fulfilled the criteria for CKD. Conclusion: This is the largest study of renal function in patients receiving long‐term HPN. After the first year following HPN initiation, the rate of decline in eGFR was similar to that expected in the general population. These findings should reassure patients and clinicians that close monitoring of renal function can lead to good outcomes. [ABSTRACT FROM AUTHOR]

Background: Cutaneous manifestations of drug‐induced type IV reactions vary widely, with symmetrical drug‐related intertriginous and flexural exanthema (SDRIFE) being a less common presentation. Corticosteroids (CS), primarily known for their anti‐inflammatory effects, rarely induce hypersensitivity reactions. Objective: The aim of this case series is to report four cases of SDRIFE following systemic prednisolone therapy and to review existing CS classification proposals to better understand cross‐reactivity of CS. Patients/Methods: Patients recruited at a German dermatology centre underwent allergologic evaluation including prick and patch testing with various CS. Positive cases underwent oral challenge testing with alternative agents. The classification systems of Coopman et al. and Baeck et al. were taken into account. Discussion: Despite a paucity of literature, CS‐induced type IV reactions do occur, including SDRIFE. Classification systems based on chemical structure provide insight into cross‐reactivity patterns. Provocation tests with alternative CS highlight the complexity of managing CS hypersensitivity. Conclusion: SDRIFE may develop following systemic prednisolone therapy. Classification systems are helpful in understanding cross‐reactivity and help in the selection of alternative preparations but are not always reliable. Individualised assessment is crucial for managing CS hypersensitivity, with consideration of alternative agents and emergency use of CS when necessary. [ABSTRACT FROM AUTHOR]

Many Australians who work outdoors (notably, farmers and graziers) routinely kill venomous snakes. We argue that this attitude is misguided and dangerous. Despite their fearsome reputation, venomous Australian snakes pose little risk to human health (snakes kill an average of less than three people per year in Australia). Also, snakes confer a substantial benefit by consuming agricultural pests such as rodents. We estimate the magnitude of that benefit with data on snake diets, feeding rates and abundances. The most valuable rodent‐controllers are Brownsnakes (genus Pseudonaja), which are rodent‐specialists as adults and are abundant in agroecosystems across much of Australia. We calculate that a free‐living adult Eastern Brownsnake consumes at least 50 mice per year (probably twice that number), and that population densities of Brownsnakes in agricultural areas can exceed 100 per km2. Thus, Brownsnakes remove thousands of mice per square kilometre of farmland per year. That offtake plausibly reduces rodent densities because Brownsnakes take all age classes and both sexes of rodents by hunting in burrows. Tolerating Brownsnakes also would benefit the environment (e.g. less reliance on toxic chemicals) and the health of humans and domestic pets (fewer rodent‐mediated diseases) and counter‐intuitively, might reduce rates of snakebite (because many bites occur when a snake is attacked). In summary, a societal policy of coexisting with highly venomous snakes would confer multiple benefits to Australian farmers. [ABSTRACT FROM AUTHOR]

Survival analysis is a fundamental area of focus in biomedical research, particularly in the context of personalized medicine. This prominence is due to the increasing prevalence of large and high‐dimensional datasets, such as omics and medical image data. However, the literature on nonlinear regression algorithms and variable selection techniques for interval‐censoring is either limited or nonexistent, particularly in the context of neural networks. Our objective is to introduce a novel predictive framework tailored for interval‐censored regression tasks, rooted in Accelerated Failure Time (AFT) models. Our strategy comprises two key components: (i) a variable selection phase leveraging recent advances on sparse neural network architectures; (ii) a regression model targeting prediction of the interval‐censored response. To assess the performance of our novel algorithm, we conducted a comprehensive evaluation through both numerical experiments and real‐world applications that encompass scenarios related to diabetes and physical activity. Our results outperform traditional AFT algorithms, particularly in scenarios featuring nonlinear relationships. [ABSTRACT FROM AUTHOR]

All‐small‐molecule organic solar cells (ASM‐OSCs) offer advantages like well‐defined molecular structures and excellent reproducibility. However, lower photovoltaic efficiencies hinder their adoption due to limitations in designing small molecular electron donors (SMEDs) with optimal energy levels, light absorption, and optoelectronic properties. The present study addresses this gap by rationally designing a series of SMEDs (DBT‐2FA1 to DBT‐2FA6) through terminal acceptors engineering into dibenzothiophene core with diphenylamine side donors for potential applications in ASM‐OSCs. Density functional theory simulations are carried‐out to establish structure‐property relationships based on structural, electrochemical, photophysical, and charge transfer (CT) properties. Results show that the SMEDs exhibit low‐lying HOMOs for suitable energy level alignment with benchmark Y6 acceptor, promoting open‐circuit voltage and charge separation. The panchromatic absorption spectra covering Vis‐NIR region and maximum light harvesting efficiency are beneficial for high current‐density in ASM‐OSCs. Notably, the push‐pull mechanism within SMEDs results in dominant intramolecular CT with above 70% CT excitations. Whereas, a moderate variation in dipole moments and electrostatic potential differences with acceptor material led to 99.9% intermolecular CT, thus ensuring robust exciton dissociation and efficient photocurrent generation. Overall, this work provides a molecular‐level understanding of designing novel SMEDs and their compatibility with acceptor materials for developing future high‐performance ASM‐OSCs. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. Methods: We included adult patients with BD‐I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. Results: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). Conclusions: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples. [ABSTRACT FROM AUTHOR]

Aims: We aimed to analyse the characteristics and in‐hospital outcomes of patients hospitalized for heart failure (HF) with co‐morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. Methods and results: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co‐morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in‐hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co‐morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in‐hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60–2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in‐hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44–2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05–0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: −4780 to 5178; P = 0.93). Conclusions: In patients hospitalized for HF, those with SSc were noted to have higher odds of in‐hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co‐morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Best practice of infection prevention and control (IPC) is a hallmark for the patient care in health care settings, but it is a major problem in developing countries like Ethiopia where resources are limited. Ethiopia Federal Ministry of Health working to strengthen its IPC program, but still it there is no organized study conducted on assessment of performance gaps and implementation challenges of IPC practice faced by hospital staffs particularly among sanitary workers (SWs) at public hospitals inline to national and international guidelines. Aim: This study focuses on compliance and determinants of IPC among sanitary worker in public hospitals in eastern Ethiopia: A cross sectional study design. Method: A cross‐sectional study was conducted among 809 SWs and eight IPC experts in public hospitals, eastern Ethiopia, from May to August 2023. A standard questionnaire was used to collect data. Face‐to‐face interview was conducted. Ten (10) question pursued to answer YES/NO were prepared. The cut point for categories of IPC practice was 1: Good (16–20 scores), 2: Fair (10–15 scores), and 3: Poor (<10 scores). The cut point for compliance and noncompliance of IPC practice among hospitals was mean (500.1). Multi‐level ordinal logistic regression models was applied to explore the association of dependent and independent variables at individual level (Model 1), hospital level (Model 2) and at both (Model 3). Crude odds ratio (COR) and adjusted odds ratio (AOR) at 95% confidence interval (CI) were used to report the result. Result: The compliance of IPC practice among SWs was 36.21% (32.72, 39.82%). The Multilevel ordinal logistic regression model shows that SWs who have good knowledge of IPC trend (AOR: 4.70, 95% CI: 2.11–10.46), SWs who are not addictive with alcohol (AOR: 2.35, 95% CI: 1.15,4.78) and chew Khat (AOR: 1.62, 95% CI: 1.06,2.46) and smoke cigarette (AOR: 3.15, 95% CI: 2.35–5.41), and SWs without job stress (AOR: 1.46, 95% CI: 0.86–2.48) were more compliant to IPC practice. Similarly, those who do not have workload (AOR: 2.74, 95% CI: 1.56–4.82), work <8 h/day (AOR: 1.46, 95% CI: 0.92–2.30), and those who have good social recognition in hospitals (AOR: 6.08, 95% CI: 4.24–8.71) were more likely to increase the compliance of IPC practice among SWs. The multilevel random‐effect model revealed 93.71% of the variability of compliance of IPC practice explained by both individual and hospital level factors. Conclusion: The overall study found that inadequate IPC practice was reported among SWs as well as by IPC experts due to poor knowledge of IPC trend and individual behaviors and working environment. Thus, the study advised that hospitals have to develop and establish IPC implementation guidelines in order to solve the concerns among these groups; national IPC office should follow its implementation across health care settings particularly at public hospitals. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence and sociodemographic and clinical risk factors associated with birth asphyxia and the immediate neonatal outcomes of birth asphyxia in Nigeria. Design: Secondary analysis of data from the Maternal and Perinatal Database for Quality, Equity and Dignity Programme. Setting: Fifty‐four consenting referral‐level hospitals (48 public and six private) across the six geopolitical zones of Nigeria. Population: Women (and their babies) who were admitted for delivery in the facilities between 1 September 2019 and 31 August 2020. Methods: Data were extracted and analysed on prevalence and sociodemographic and clinical factors associated with birth asphyxia and the immediate perinatal outcomes. Multilevel logistic regression modelling was used to ascertain the factors associated with birth asphyxia. Main outcome measures: Incidence, case fatality rate and factors associated with birth asphyxia. Results: Of the available data, 65 383 (91.1%) women and 67 602 (90.9%) babies had complete data and were included in the analysis. The incidence of birth asphyxia was 3.0% (2027/67 602) and the case fatality rate was 16.8% (339/2022). The risk factors for birth asphyxia were uterine rupture, pre‐eclampsia/eclampsia, abruptio placentae/placenta praevia, birth trauma, fetal distress and congenital anomaly. The following factors were independently associated with a risk of birth asphyxia: maternal age, woman's education level, husband's occupation, parity, antenatal care, referral status, cadre of health professional present at the birth, sex of the newborn, birthweight and mode of birth. Common adverse neonatal outcomes included: admission to a special care baby unit (SCBU), 88.4%; early neonatal death, 14.2%; neonatal sepsis, 4.5%; and respiratory distress, 4.4%. Conclusions: The incidence of reported birth asphyxia in the participating facilities was low, with around one in six or seven babies with birth asphyxia dying. Factors associated with birth asphyxia included sociodemographic and clinical considerations, underscoring a need for a comprehensive approach focused on the empowerment of women and ensuring access to quality antenatal, intrapartum and postnatal care. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence, perinatal outcomes and factors associated with neonatal sepsis in referral‐level facilities across Nigeria. Design: Secondary analysis of data from the Maternal and Perinatal Database for Quality, Equity and Dignity Programme in 54 referral‐level hospitals across Nigeria. Setting: Records covering the period from 1 September 2019 to 31 August 2020. Population: Mothers admitted for birth during the study period, and their live newborns. Methods: Analysis of prevalence and sociodemographic and clinical factors associated with neonatal sepsis and perinatal outcomes. Multilevel logistic regression modelling identified factors associated with neonatal sepsis. Main outcome measures: Neonatal sepsis and perinatal outcomes. Results: The prevalence of neonatal sepsis was 16.3 (95% CI 15.3–17.2) per 1000 live births (1113/68 459) with a 10.3% (115/1113) case fatality rate. Limited education, unemployment or employment in sales/trading/manual jobs, nulliparity/grand multiparity, chronic medical disorder, lack of antenatal care (ANC) or ANC outside the birthing hospital and referral for birth increased the odds of neonatal sepsis. Birthweight of <2500 g, non‐spontaneous vaginal birth, preterm birth, prolonged rupture of membranes, APGAR score of <7 at 5 min, birth asphyxia, birth trauma or jaundice were associated with neonatal sepsis. Neonates with sepsis were more frequently admitted to a neonatal intensive care unit (1037/1110, 93.4% vs 8237/67 346, 12.2%) and experienced a higher rate of death (115/1113, 10.3% vs 933/67 343, 1.4%). Conclusions: Neonatal sepsis remains a critical challenge in neonatal care, underscored by its high prevalence and mortality rate. The identification of maternal and neonatal risk factors underscores the importance of improved access to education and employment for women and targeted interventions in antenatal and intrapartum care. [ABSTRACT FROM AUTHOR]

Aims: Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self‐management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. Methods and results: The VECTOR‐HF I and IIa studies are prospective, single‐arm, open‐label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)‐guided HF management using PSM in New York Heart Association class II and III HF patients. Physician‐prescribed LAP thresholds trigger patient self‐adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure‐ or device‐related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6‐min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. Conclusions: Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations. [ABSTRACT FROM AUTHOR]

Introduction: Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. Patients and methods: The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non‐surgical methods failed. Results: Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10–90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10–90) to 15 degrees (range: 0–40), with only minor loss of flexion from 105 (range: 60–155) to 90 degrees (range: 30–150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non‐surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. Conclusion: This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non‐surgical methods, even without prophylactic factor replacement. [ABSTRACT FROM AUTHOR]

Summary: Containers have taken over large swaths of cloud computing as the most convenient way of packaging and deploying applications. The features that containers offer for packaging and deploying applications translate to high performance computing (HPC) as well. At The National Oceanic and Atmospheric Administration, containers provide an easy way to build and distribute complex HPC applications, allowing faster collaboration, portability, and experiment computer environment reproducibility amongst the scientific community. The challenge arises when applications rely on message passing interface (MPI). This necessitates investigation into how to properly run these applications with their own unique requirements and produce performance on par with native runs. We investigate the MPI performance for benchmarks and containerized climate models for various containers covering selection of compiler and MPI library combinations from the Cray provided programming environments on the Cray XC supercomputer GAEA. Performance from the benchmarks and the climate models shows that for the most part containerized applications perform on par with the natively built applications when the system optimized Cray MPICH libraries are bound into the container, and the hybrid model containers have poor performance in comparison. We also describe several challenges and our solutions in running these containers, particularly challenges with heterogeneous jobs for the containerized model runs. [ABSTRACT FROM AUTHOR]

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6–14 years‐old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole‐brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone‐related effects in theta (4–7 Hz) and alpha (8–14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left‐lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex‐specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age. [ABSTRACT FROM AUTHOR]

Key points Heart failure (HF) is a heterogeneous condition that can be categorized according to the left ventricular ejection fraction (EF) into HF with reduced (HFrEF) or preserved (HFpEF) EF. Although HFrEF and HFpEF share some common clinical manifestations, the mechanisms underlying each phenotype are often found to be distinct. Identifying shared and divergent pathophysiological features might expand our insights on HF pathophysiology and assist the search for therapies for each HF subtype. In this study, we evaluated and contrasted two new murine models of non‐ischaemic HFrEF and cardiometabolic HFpEF in terms of myocardial structure, left ventricular function, gene expression, cardiomyocyte calcium handling, mitochondrial polarization and protein acetylation in a head‐to‐head fashion. We found that in conditions of similar haemodynamic stress, the HFrEF myocardium underwent a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation was greater in the HFpEF myocardium. We observed opposing features on calcium release, which was diminished in the HFrEF cardiomyocyte but enhanced in the HFpEF cardiomyocyte. Mitochondria were less polarized in both HFrEF and HFpEF cardiomyocytes, reflecting similarly impaired metabolic capacity. Hyperacetylation of cardiac proteins was observed in both models, but it was more accentuated in the HFpEF heart. Despite shared features, unique triggering mechanisms (neurohormonal overactivation in HFrEF vs. inflammation in HFpEF) appear to determine the distinct phenotypes of HF. The findings of the present research stress the need for further exploration of the differential mechanisms underlying each HF subtype, because they might require specific therapeutic interventions. The mechanisms underlying heart failure with either reduced (HFrEF) or preserved (HFpEF) ejection fraction are often found to be different. Previous studies comparing pathophysiological traits between HFrEF and HFpEF have been conducted on animals of different ages and strains. The present research contrasted two age‐matched mouse models of non‐ischaemic HFrEF and cardiometabolic HFpEF to uncover divergent and shared features. We found that upon similar haemodynamic stress, the HFrEF heart experienced a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation appeared to be greater in the HFpEF myocardium. Calcium release was diminished in the HFrEF cardiomyocyte and enhanced in the HFpEF cardiomyocyte. Mitochondria were comparably less polarized in both HFrEF and HFpEF myocytes. Hyperacetylation of proteins was common to both models, but stronger in the HFpEF heart. Casting light on common and distinguishing features might ease the quest for phenotype‐specific therapies for heart failure patients. [ABSTRACT FROM AUTHOR]

This article is concerned with sample size determination methodology for prediction models. We propose to combine the individual calculations via learning‐type curves. We suggest two distinct ways of doing so, a deterministic skeleton of a learning curve and a Gaussian process centered upon its deterministic counterpart. We employ several learning algorithms for modeling the primary endpoint and distinct measures for trial efficacy. We find that the performance may vary with the sample size, but borrowing information across sample size universally improves the performance of such calculations. The Gaussian process‐based learning curve appears more robust and statistically efficient, while computational efficiency is comparable. We suggest that anchoring against historical evidence when extrapolating sample sizes should be adopted when such data are available. The methods are illustrated on binary and survival endpoints. [ABSTRACT FROM AUTHOR]

Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions. Synopsis: Three molecules of cardiolipin, the signature mitochondrial phospholipid, tightly interact with the ADP/ATP carrier (AAC/ANT). This study demonstrates that each cardiolipin-AAC/ANT interaction is structurally and functionally important. Negatively charged mutations into the cardiolipin binding sites of yeast Aac2 disrupted cardiolipin-Aac2 interaction. Aac2 tertiary structure was destabilized in the mutants with disrupted cardiolipin binding. Disruption of cardiolipin binding impaired Aac2 transport activity in a site-specific manner. A disease-associated mutation in human ANT1 compromises ANT1 structure and transport activity due to a disturbed cardiolipin-ANT1 interaction. The binding of three cardiolipin molecules to the mitochondrial ADP/ATP carrier supports the protein's tertiary structure and transport activity. [ABSTRACT FROM AUTHOR]