Objective To describe sedative co-medication patterns across frailty states (robust, prefrail, frail) in people living with HIV using network-based analysis, aiming to identify key medication interactions and network drivers that can guide safer therapeutic approaches. Methods This cross-sectional study analyzed 321 participants using sedatives from the Positive Brain Health Now Cohort (mean age: 53 years), categorized as robust (30.2%), prefrail (47.0%), or frail (22.7%). Sedative use was classified using the Sedative Load Model, and frailty was assessed with a modified Fried Frailty Phenotype. Co-medication networks were constructed for robust, prefrail, and frail groups, with metrics such as Neighborhood Shift Scores (NESH) and Delta Betweenness used to evaluate network dynamics. Edge-level Observed-to-Expected (O/E) ratios highlighted significant co-prescription patterns and associated drug-drug interactions. Results Frail individuals exhibited the most interconnected network, characterized by higher graph density and average degree compared to robust and prefrail groups. Key ”driver” medications identified were mirtazapine (robust-to-prefrail), gabapentin (robust-to-frail), and pregabalin (prefrail-to-frail). In frail individuals, medication pairs with high O/E ratios (e.g., hydromorphone-clonazepam, O/E: 3.07), posed a potential risk for severe drug interactions requiring therapy modification. Robust individuals displayed fewer and less severe drug interactions, whereas prefrail individuals exhibited an intermediate level of complexity. Conclusion Sedative co-medication patterns vary significantly across frailty states in people with HIV, with frailty amplifying risks of severe drug interactions. Identifying key medications as network drivers provides actionable insights to optimize therapeutic approaches, particularly for depression and neuropathic pain management in prefrail and frail stages.

Isolated central nervous system (CNS) involvement due to posttransplantation proliferative disorder (PTLD) is even rarer , with only a few cases reported in the literature.. CNS involvement in patients with mature B-cell non-Hodgkin’s (NHL) and PTLD confers a significantly worse prognosis as compared to patients without CNS lymphoma disease. Treatment of primary CNS lymphoma (PCNSL) is challenging due to resistance to conventional cytotoxic and intrathecal chemotherapy. Here, we report the successful use of intrathecal rituximab in two pediatric cases of CD20+ isolated CNSL that had failed to respond to standard chemotherapy, intravenous rituximab and Epstein-Barr virus (EBV)-specific cellular therapy. However, after repeated intrathecal administration of rituximab, both patients’ clinical symptoms were alleviated, which has created opportunities for further treatments. We emphasise that intrathecal rituximab may be a safe and effective option for the treatment of pediatric CNSL. The literature on this topic was also reviewed.

Background Cancer is the third-leading cause of death in the United Arab Emirates (UAE). There are few studies on cancer epidemiology in the UAE. Methods This retrospective study, from 2011 to 2013 until 2023, aimed to estimate the prevalence of a history of cancer and lifetime risk and identify its risk factors. Results Among 8635 cancer-free participants at the time of screening, 209 were diagnosed with new cancer (2.5%) over the follow-up period, 129 (1.9%) females compared to 80 (0.9%) males. The most common type of cancer was Breast cancer, with an incidence of 18% ( 37 cases ) out of the 209 total cases, all females. The second most common type was Thyroid Cancer, with 31 cases; 24 of them were females, and 7 were males. The third most common type was colon cancer, with 22 cases, 11 females and 11 males. Other types of cancer were found but had lower incidence, such as Adrenal, skin cancer, ovarian, bladder, and gastrointestinal GI cancers. The prevalence was comparable to the latest published report of the Abu Dhabi cancer registry in 2019. Among the whole cohort, Cox regression analysis showed only age and higher levels of HDL as risk factors for any cancer after screening when including possible risk factors that were assessed at baseline. The risk increases by 4.8% for each year older and 52% for each unit increase in HDL. The area Under the ROC Curve of the developed model for predicting any cancer type is 0.739 (0.707-0.771). Conclusion This study calls for focused research on different types of cancer to identify significant predictors to aid early diagnosis and management, as well as research on prevention and survival. This study’s results provide critical input to the country’s decision-makers on cancer services and are informative internationally as the risk factors identified are prevalent worldwide and may be targeted with available interventions.

The chemical balance between essential nutrients and defense compounds in plants determines the quality of the forage available to herbivores and can be modified by both environmental conditions and herbivores themselves. We investigated whether climate and herbivory affect nutrient and defense compound concentrations across plant functional groups. Concentrations of nutrients - nitrogen (N) and phosphorus (P) - and defense compounds - silicon (Si) and phenolics (Ph) - were measured in plant samples from the locally most abundant species, collected in northern Norway across a gradient in summer temperature and different reindeer grazing regimes. Nutrient and defense compound concentrations varied substantially across species and plant functional groups. In addition, nutrients (N, P) declined over the summer, while defense compounds (Si, Ph) accumulated. Sites with a warmer climate had a stronger decrease in nutrient concentrations over the season. We found no evidence that long-term contrasts in reindeer herbivory intensity affected the average nutritional quality within plant species. Overall, our results suggest that spatial variation in the nutritional quality in Arctic tundra vegetation is mainly determined by the species composition and by consistent changes over the summer season. In comparison, reindeer herbivory and local climate seem to have relatively little impact on the average nutrient and defense compound concentrations of the plant species, suggesting they mainly alter forage quality through effects on functional and taxonomic composition of the vegetation.

Abstract: Aims: This study aimed to determine the venetoclax (VEN) concentration in patients, analyse its correlation with adverse events (AEs), and assess the effects of combined medications on both VEN concentration and concentration-related AEs. Methods: The concentrations of VEN in 114 enrolled patients were measured. Among these patients, 52 were treated with single-agent VEN, 20 with VEN in combination with omeprazole (OPZ), 20 with VEN combined with voriconazole (VCZ), and 22 with VEN in conjunction with posaconazole (PCZ). The relevant data were subjected to statistical analysis. Results: Concentration/daily dose ratio (C/D) for the minimum (C min) and maximum (C max) concentrations of VEN were negatively correlated with white blood cell count (WBC) and neutrophil count (NEUT) but positively correlated with lactate dehydrogenase (LDH). The effect of combined medications on VEN concentration: VEN + PCZ group/VEN + VCZ group > VEN + OPZ group > VEN group. When the C max (C/D) value of VEN is 11.21, it has the highest predictive value for reducing AEs in patients with grade ≥3 NEUT. Conclusion: Increased VEN concentration increased the incidence of grade 3 or higher haematological adverse events in patients. CYP3A inhibitors significantly increased VEN levels, thereby increasing the risk of AEs.

Haitians have a high incidence of sickle cell disease (SCD), but limited healthcare resources. The Comparative Study of Children in Haiti and Miami with Sickle Cell Disease (CSHSCD) (NIH R01HL149121) assessed clinical and social characteristics of children of Haitian immigrants and African American controls and compared them with Haitian children living in Haiti. We hypothesized that there would be significant differences and that differences in the Haitian American group may be related to time since immigrating. For this report, baseline characteristics of a total of 255 children (mean age 38 months; 204 Haitians, 32 Haitian American and 19 African American) were compared as well as parental self-reported barriers to care and acculturation. Children with hemoglobin SS in Miami of either African American or Haitian ethnicities were more likely receiving hydroxyurea (p<0.001) and less likely have experienced a vaso-occlusive crisis (p<0.001) compared to children in Haiti. Being in the United States over 10 years was associated acculturation and better English proficiency. Children in Haiti were more anemic, more likely to be malnourished, and to have incomplete pneumococcal conjugate vaccinations. Haitian families faced issues affording treatment. Longer length of stay in the United States was associated with appropriate pneumococcal vaccination, higher parental education, and better English competency. Haitians living in Haiti were at a significant disadvantage in every aspect of care, requiring ongoing assistance. We encourage global partnerships to decrease barriers to care in disadvantaged populations.

Global climate change exerts profound impacts on biodiversity and species distribution, potentially leading to habitat contraction and species extinction. As an endemic vulnerable species listed under China’s National Class II Protected Animals, the tufted deer (Elaphodus cephalophus) lacks comprehensive predictions regarding its future distribution under climate change. This study employs an optimized MaxEnt model integrated with 19 climatic variables and environmental factors (topography, vegetation, and anthropogenic disturbances) to systematically predict the species’ potential habitat distribution across China. Through parameter screening of 248 combinations using the Kuenm package, the optimal model configuration (FC=QH, RM=2.5) achieved exceptional predictive accuracy (AUC = 0.977 ± 0.002). Key findings include: (1) Current suitable habitats span 145.98×104 km², predominantly clustered in the Sichuan-Guizhou-Yunnan mountainous regions and the Qinling-Daba-Wuling ranges; (2) Annual precipitation (Bio12, 33.2%), elevation (18.7%), slope (14.5%), temperature annual range (Bio7, 9.2%), NDVI (7.9%), and temperature seasonality (Bio4, 7.5%) emerged as critical limiting factors; (3) Projected habitat areas under future climate scenarios will contract by 21.8%-28.4%, with shrinkage concentrated in eastern low-elevation zones and expansion toward the eastern Qinghai-Tibet Plateau; (4) Habitat centroids exhibit significant westward shifts, reaching 141.8 km under SSP585 (2090s). This study provides theoretical foundations for conserving Elaphodus cephalophus genetic resources and climate-adaptive management, emphasizing the urgency to prioritize ecological corridor construction in western Sichuan-southeastern Tibet.

Objective: To examine how eicosanoid levels in menstrual effluent of adolescents within three years of menarche relate to the severity of menstrual pain. Design: Prospective cohort study. Setting: Community teaching hospital. Population: Adolescents within three years after menarche. Methods: Participants provided a menstrual effluent sample between 4 and 30 months after menarche. Eicosanoids and oxylipins concentrations were measured in the menstrual effluent. We compared effluent concentrations of participants with dysmenorrhea (>0 on a 0-10 scale, n=33) to age-matched pain-free controls (0 on a 0-10 scale, n=18). Main Outcome Measures: Eicosanoid and oxylipins concentrations in menstrual effluent. Results: Participants with dysmenorrhea had higher PGF2α (4.5 [1.6, 8.9] ng/ml, p=0.014) than controls (1.1 [0.07, 4.4] ng/ml). However, differences in PGE2 (7.1 [2.6, 10.1] vs. 3.5 [1.0, 5.1], p=0.053) and 12-HETE (36.3 [23.7, 60.7] vs. 29.6 [13.4, 51.5], p=0.305) were not significant. The correlations between PGF2α (r=0.37, p=0.004) or PGE2 concentration (r=0.28, p=0.046) and menstrual pain intensity were moderate to small. Overall, there were positive correlations between menstrual volume and eicosanoid concentrations (r’s >0.4, p’s< 0.001). Intriguingly, dysmenorrhea participants taking analgesics had a high total content of PGF2α (66.2 [43.0,164.7]) compared to controls (19.1 [6.0,47.5], p=0.04). LC-MS/MS revealed higher concentrations of 12-HETE, 14,15-EET, 15-HETE, 18cdLTB4, LTB4, and PGF2α—and lower 6-kPGF1α—in the effluent of dysmenorrhea participants compared to controls. Conclusions: Elevated PGF2α in adolescents with dysmenorrhea, modest correlations between prostaglandin concentrations and menstrual pain, and the identification of additional oxylipins suggest that inflammatory processes beyond the prostaglandin pathway may contribute to dysmenorrhea.

Current sheets are quasi-1D layers of strong current density, which play a crucial role in storing magnetic field energy and subsequently releasing it through charged particle acceleration and plasma heating. They are observed in planetary magnetospheres and solar wind flows, where they are also known as solar wind discontinuities. Despite significant variations in plasma parameters across different magnetospheres and the solar wind, current sheet configurations can remain fundamentally similar. In this study, we analyze current sheets observed in various regions, including the near-Earth (within 30 Earth radii) and distant (50-200 Earth radii) magnetotail, Earth’s dayside and nightside magnetosheath, the near-Earth solar wind, and Martian and Jovian magnetotails. We examine three key plasma parameters: the plasma beta (ratio of plasma to magnetic pressure), the Alfvénic Mach number (ratio of plasma bulk flow speed to Alfvén speed in the current sheet reference frame), and the ion to electron temperature ratio. Additionally, we investigate the kinetic, thermal, and magnetic field energy densities. Our cross-system analysis demonstrates that the same current sheet configuration can exist across a very wide parametric space spanning multiple orders of magnitude. We also highlight the distinct plasma environments of the Martian and Jovian magnetotails, characterized by large populations of heavy ions, emphasizing their significance in comparative magnetospheric studies.

Arctic marine cold air outbreaks (CAOs) generate distinct and dynamic cloud regimes due to intense air-sea interactions. To understand the temporal evolution of CAO cloud properties and compare different CAO events, a Lagrangian perspective is particularly useful. We developed a novel technique that enables the conversion of inherently Eulerian satellite data into a Lagrangian framework, combining the broad spatiotemporal coverage of satellite observations with the advantages of Lagrangian tracking. This technique was applied to eight CAO cases associated with a recent field campaign. Our results reveal a striking contrast among the cases in terms of cloud-top phase transitions, providing new insights into the evolution of CAO cloud properties.

This study focuses on developing a constitutive model to describe the dynamic plasticity and fracture behavior of arc-melted cladding for remanufacturing wind turbine gears. By combining quasi-static tensile tests and Split Hopkinson Tension Bar (SHTB) experiments, the research investigates the static and dynamic properties of Wire Arc Additive Manufacturing (WAAM) alloy cladding under various strain rates and high temperatures. Results reveal strain hardening, strain rate hardening, and thermal softening effects, leading to the establishment of J-C plasticity and failure equations. Finite element simulations validate the model, achieving an AARE of 8.670% and an R value of 0.9449, confirming the model’s accuracy and reliability for predicting the alloy’s dynamic behavior in remanufacturing applications.

This paper describes the topology and operation of a new family of asynchronous frequency dividers called Fractional Digital Regenerative Frequency Dividers (FDRFD). The operation is explained using a digital approach in the time domain and compared to the closest analog equivalent. The fractional behavior is intrinsic to the topology without the need for an external modulator. Integer ratios are also easily obtained and can serve as multimodulus dividers when required. Starting with the elementary version of this kind of divider, a generalization is made with repeated cell patterns in the closed loop for finer control of the fractional ratio. Some measurements on an FPGA-based implementation are provided to validate the theoretical study.

The use of physical models to predict patterns of organismal growth has long interested biologists. Models based on hydraulic or biomechanical principles have been invoked to predict the scaling of tree branching networks, but most assume self-similarity throughout the branching networks and do not consider more than a single physics-based constraint. A more recent model, however, predicts that the allometry of terminal tree branches will differ from the bole and more basal branches. In this model, terminal branch allometry will center around values derived from hydraulic considerations, and differ from the expectations of biomechanical models. Here we evaluate the predictions of this model for the growth of the terminal stems of woody plants using data from 52 species sampled across the seed plant phylogeny and spanning over four orders of magnitude in stem size. We find that the slopes describing terminal stem allometry across seed plants are strongly conserved, despite nearly 400 million years of divergent evolution across the examined lineages. Phylogenetic analysis reveals a strong “pull” towards optimal values, largely consistent with the hydraulic model’s predictions. Our results suggest that the ontogeny of terminal stems in seed plants follow similar allometric scaling rules which operate across evolutionary and ecological scales.

Version control system tools empower developers to independently work on their development tasks. These tools also facilitate the integration of changes through merging operations, and report textual conflicts. However, when developers integrate their changes, they might encounter other types of conflicts that are not detected by current merge tools. In this paper, we focus on detecting dynamic semantic conflicts, which occur when a merging scenario does not lead to textual conflicts but results in undesired interference---causing unexpected program behavior at runtime. To address this issue, we propose a lightweight technique that explores the use of static analysis to detect interference when merging contributions from two developers. We evaluate our technique using a dataset of 99 experimental units we curated from merge scenarios of GitHub projects. The results provide evidence that our technique presents significant interference detection capability. It outperforms, in terms of F1-score and recall, techniques that rely on testing-based analysis, but these show better precision. Our technique precision is comparable to the ones observed in other studies that leverage static analysis or theorem proving to detect semantic conflicts, albeit with significantly improved execution performance. Our technique often takes less than a minute to analyze a merge scenario, while other static and dynamic analysis techniques often take tens of minutes or hours to complete the same task.

This paper presents a novel ethical framework for artificial intelligence (AI), termed "Raqib and Atid," inspired by Islamic concepts of thought, intention, and action. Drawing on Islamic principles and leveraging blockchain technology, this framework monitors an AI's internal processes ("thoughts"), planned actions ("intentions"), and executed actions to ensure comprehensive accountability. Just as the angels Raqib and Atid maintain a celestial record for divine judgment, this framework systematically documents an AI's operations, generating an unalterable history of its activity. To guarantee the integrity and transparency of this data, it is suggested that these logs be secured on a blockchain. This record is preserved for a metaphorical "Day of Judgment"-an evaluation process that occurs at the end of the AI's operational life, ensuring accountability even after the AI is no longer functional. By analyzing the AI's data, the system can proactively identify potential ethical violations, provide feedback, and promote continuous learning. This approach offers a more comprehensive way to ensure responsible AI development. The framework addresses challenges in defining "intention" for AI and balancing internal monitoring with AI autonomy, providing a promising path towards building ethical and responsible AI systems aligned with human values

Intestinal Obstruction Secondary to Strangulated Obturator Hernia: A Case Report.

Abstract Background Although a complexity theory lens can help to understand national policy implementation at a local government level, application of this lens often remains metaphorical. We illustrate how complexity concepts (adaptation, feedback, emergence and co-evolution) can be used practically in research on policy implementation using a UK case study (Future in Mind; FiM), aimed at improving children’s access to mental health services in a municipality in northern England. Methods We re-analysed interview data with staff from local government, the National Health Service, schools, and the voluntary and community sector (n=31) involved in implementing FiM and coded this data in NVivo12 using complexity concepts as sensitising constructs. Findings We identified 5 feedback loops: two positives (1. flexing the training offer; 2. new skills, knowledge and behaviour by non-specialist staff) and three negatives (3. short termism, 4. free rider behaviour, 5. professional boundaries). These loops energised local adaptations of FiM by school and NHS staff, leading to system-level change (emergence), with the school system becoming more responsive to the mental wellbeing needs of children and young people, and shifts across systems (co-evolution), by developing joint values and language between schools and NHS. Conclusions We demonstrate the importance of positive and negative feedback loops for evidencing system-level change and shifts across systems. Our findings provide new insights into unintended consequences of policy implementation and starting positions for implementers to utilise feedback for generating impact. We argue for blurring of boundaries between implementation and evaluation in policy research to optimise the use of feedback.

Background A comprehensive performance management system is a key component to a healthcare organization’s success in providing financially sustainable quality care. It supports the recruitment and retention of competent and motivated clinical staff by allowing for a system of accountability that can support deficiencies, compensate for shortcomings, and invest in successes. Privatization, increased patient health demands and expectations, rapid technological advancements and medical science developments have improved the quality and longevity of life, but nonetheless, pose serious financial challenges for healthcare organizations. An academic center in a high-income country explored the impact of relative value units to measure productivity and assist with resource planning as a possible solution to market competitivity. Case To implement the initiative, the teaching hospital associated all non-medication orders with the relevant current procedural terminology codes and associated the codes with relative value units. The overall implementation of the performance system was divided into multiple phases, where the first constituted the technical software builds and integrations, followed by a pilot phase, and finally, a phase for outlining and defining the administrative requirements, including guidelines, methods, policies, and rules that would govern the layers and mechanisms of accountability surrounding the use of relative value units in managing clinicians’ productivity, specifically physicians. The case focuses on the technical setup of the management system that entailed a series of validations and verifications to confirm the accuracy of the integration and communication between the electronic medical record (EMR) and the organization’s data extraction and representation software, as well as ensuring all data generated by the software matches the data available on the physician interface of the EMR. Conclusion A universally recognized approach developed by medical personnel to manage physician performance contributes to and improves and organization’s resource planning and decision-making capacities, especially in targeted recruitment and effective retention strategies. Other benefits of adopting such systems are their compatibility with modern EMRs and their potential to reduce resistance to change, due to the objectivity associated with adopting a system that quantifies physicians’ work based on time and complexity reviewed and determined by physicians rather than persons outside the medical field.

This article argues that artificial intelligence (AI), when wielded by independent and unaffiliated researchers, can become a weapon to shatter academic monopolies, challenge technocracy, and revive human values. By examining the links between decentralization, class-based oppression, and the erosion of ethics in modern societies, this work demonstrates how AI can relocate intellectual discourse from the ivory towers of academia to the streets, fostering a global movement to democratize truth.

Topology

We developed MULTICOM4, the latest version of the MULTICOM system, to improve protein complex structure prediction by integrating transformer-based AlphaFold2, diffusion model-based AlphaFold3, and our in-house techniques. These include protein complex stoichiometry prediction, diverse multiple sequence alignment (MSA) generation leveraging both sequence and structure comparison, modeling exception handling, and deep learning-based model quality assessment. MULTICOM4 was blindly evaluated in the 16th community-wide Critical Assessment of Techniques for Protein Structure Prediction (CASP16) in 2024. In Phase 0 of CASP16, where stoichiometry information was unavailable, MULTICOM predictors performed best, with MULTICOM_human achieving a TM-score of 0.752 and a DockQ score of 0.584 for top-ranked predictions on average. In Phase 1 of CASP16, with stoichiometry information provided, MULTICOM_human remained among the top predictors, attaining a TM-score of 0.797 and a DockQ score of 0.558 on average. The CASP16 results demonstrate that integrating complementary AlphaFold2 and 3 with enhanced MSA inputs, comprehensive model ranking, exception handling, and accurate stoichiometry prediction can effectively improve protein complex structure prediction.

Purpose : Congenital diaphragmatic hernia (CDH) is a complex disease with significant morbidity and mortality. The use of echocardiography, traditionally a Pediatric Cardiology echocardiogram (PCE), has significantly advanced the management of CDH but its availability can be limited and there are concerns regarding clinical stability during the assessment. Neonatologist-performed targeted neonatal echocardiography (TNE) has been proposed as a supplementary modality in CDH. Herein, we evaluate the feasibility, safety, and potential benefits of integrating early TNE and a focused assessment protocol in CDH care. Methods : This was a retrospective, single-center study of neonates with CDH who received either an initial PCE (n = 26) or complete TNE (n = 20). The timing, images, and duration of the study were collected as well as clinical stability data. A focused TNE protocol for cases of clinical instability was developed and similarly evaluated. Results : Despite similar clinical risk predictors, TNE was performed sooner (mean 3.0 vs 11.6 hours, p < 0.0001) and quicker (mean 25.9 vs 44.4 minutes, p = 0.0001) than a PCE. While fewer images were obtained (mean 102.0 vs 143.2 images, p<0.0001), no cases of congenital heart disease were missed. TNE and PCE were equally-well tolerated. When indicated, a focused TNE protocol was utilized that provided actionable information with a mean duration of 7.2 minutes (n = 4). Conclusion : TNE can be performed early, quickly, and safely in neonates with CDH. A focused TNE protocol may be useful even in non-TNE centers for the acute care of critically ill neonates with CDH.

Background: Meconium Aspiration Syndrome (MAS) is a serious condition marked by meconium in amniotic fluid, causing respiratory distress in newborns. MAS poses risks such as pneumothorax, persistent pulmonary hypertension, and mortality, especially in full-term or post-term infants. The study focuses on understanding MAS outcomes, aiming to assess improvement post-resuscitation or identify complications leading to mortality in these infants Methods Retrospective observational study was conducted among all the cases of meconium aspiration syndrome admitted in NICU of Patan Hospital from 1st February 2016 to 1st February 2019 to determine the complication and outcome. Descriptive analysis was used to analyze the data. Result A total of 51 cases of Meconium aspiration syndrome were admitted among which 28 were male. The most common complication was determined to be sepsis (29.4%). Conclusion Meconium aspiration syndrome could be fatal and is associated with morbidities including respiratory distress, pulmonary hypertension, and sepsis.

Parkinson’s disease (PD) is considered one of the most frequent neurological brain diseases in the world. There is a need to study the early and efficient biomarkers of PD, such as changes in structural disorders like DNA/chromatin, especially at the subcellular level in the human brain. We used mesoscopic-physics-based techniques, partial wave spectroscopy (PWS), and inverse participation ratio (IPR) to probe structural alteration in the human brain tissue samples and DNA/chromatin in brain cell nuclei. Results show an increase in the structural disorder in tissues and DNA/chromatin. The rise in mass density fluctuations in the nuclei components, such as DNA/chromatin, can be linked to the aggregation of alpha-synuclein in the substantia nigra of the brain. This protein deposition is considered a significant cause of neuronal death in the brains of PD patients. We also did a histological analysis of brain tissues, which supports our results from dual photonics techniques.