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Glanzmann thrombasthenia (GT) and GT-like phenotype represent inherited platelet disorders caused by defects in platelet glycoprotein αIIbβ3 (encoded by ITGA2B and ITGB3) or RASGRP2 and FERMT3 mediated platelet intracellular signaling, respectively. While globally rare, prevalence of these bleeding phenotypes is notably higher in regions with high consanguinity, including Pakistan, with limited data on GT-associated variants. Compared to traditional diagnostic approaches, Next-generation sequencing (NGS) offers comprehensive detection of known and novel variants, enhancing diagnostic accuracy in genetic heterogeneous disorders like GT. This study investigated the mutational spectrum of GT and GT-like phenotype in 67 patients from 55 unrelated Pakistani families using a targeted gene panel. Variant annotation and pathogenicity assessments were performed using established guidelines. Structural modeling and molecular dynamics simulations were used to predict the functional consequences of selected novel variants. A total of 21 distinct variants were identified (15 in ITGA2B and 6 in ITGB3), achieving an 87.3% diagnostic yield. Ten were novel, including missense, frameshift, splice-site, and CNV variants. Two recurrent ITGA2B frameshift variants suggested possible founder effect. Analysis of RASGRP2 revealed two novel homozygous variants in GT-like cases. A genotype-phenotype association analyses suggested a severe bleeding diathesis in GT patients harboring truncating mutations in an age dependent manner, and, clinical diversity among GT patients with same genetic variant. This study expands the mutational spectrum of GT and GT-like bleeding diathesis in Pakistani population, identifying novel and recurrent mutations, which highlights the diagnostic value of NGS.

Wearable and textile-based technologies are transforming health monitoring by enabling continuous, non-invasive, and context-aware assessment of physiological and biochemical signals in daily life. Advances in flexible electronics, conductive fibers, smart materials, and artificial intelligence have driven a shift from rigid, device-centric wearables toward textile-integrated and garment-based systems capable of distributed sensing, actuation, energy harvesting, storage, and communication. This roadmap provides a textile-centric overview of the current state and future trajectory of wearable technologies for healthcare, with electronic textiles positioned as a distinct and strategically important class within the broader wearable ecosystem. We synthesize progress across textile-integrated sensing, therapeutic and protective garments, textile body-area networks, energy-autonomous systems, and embedded computing, while critically examining challenges related to signal reliability, manufacturability, scalability, data governance, regulation, and equity. Market trends and adoption patterns are discussed to contextualize translational pathways from laboratory prototypes to clinically deployable and scalable textile systems. By identifying key scientific, technological, and societal priorities, this roadmap outlines actionable directions to accelerate the integration of textile-based wearable technologies into preventive, personalized, and decentralized healthcare.

We present a genome assembly from an individual female Platyrhinus resinosus (Cramp-ball Fungus Weevil; Arthropoda; Insecta; Coleoptera; Anthribidae). The assembly contains two haplotypes with total lengths of 764.04 megabases and 758.34 megabases. Most of haplotype 1 (97.93%) is scaffolded into 11 chromosomal pseudomolecules, including the X sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 17.22 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces genomes for eukaryotic species found in Britain and Ireland.

The global mining industry is growing in footprint and continues to occupy new locations globally in support of the energy transition. Associated mining activities like land clearing, blasting and truck haulage are known to generate dust, creating a range of environmental and health hazards. However, research tracking the global spatial and temporal patterns of mine-related dust has been lacking. This study assesses global spatio-temporal patterns of mine dust and factors that influence those distributions both globally and in localized Australian contexts through generalized additive models (GAMs). Spatial patterns of mine dust are evaluated using Local Indicators of Spatial Association (LISA), and the results indicate significant geographic heterogeneity - elevated levels of Aerosol Optical Depth (AOD) were identified in tropical mining areas in South Asia, West Africa, and Southeast Asia, whereas lower levels of AOD were observed in the United States and Australia. Our statistical analysis indicates that GAMs effectively captured the variability in AOD (global R2 = 0.71; local R2 = 0.62). However, ground-based PM₁₀ measurements were a more reliable indicator of site-specific mining activity, showing a stronger relationship with mine production (r = 0.6). This study highlights key data uncertainties and complexities influencing our understanding of the impacts of mine dust beyond the local scale. Notably, it highlights an inconsistent disconnect between mines influencing regional dust levels, versus regional dust levels impacting mine operations themselves. It also underscores the importance of developing a standardized method for on-site dust monitoring at all mines worldwide and an improved network of in-situ measurement stations in support of better outcomes for the environment and human health.

Cuffless blood pressure (BP) monitoring technologies, primarily based on pulse transit time (PTT) or photoplethysmography (PPG), frequently suffer from calibration drift due to their reliance on blood volume surrogates rather than direct pressure measurement. To address this physiological limitation, this study presents a multi-modal deep learning framework that integrates superficial temporal artery tonometry (STAT), which captures high-fidelity pressure waveform morphology, with electrocardiography (ECG) and PPG signals. &#xD;&#xD;Approach: A custom wearable device was developed to simultaneously acquire these signals during dynamic perturbations. Extracted features included heart rate (HR) from ECG, PTT from ECG-PPG pairs, and BP-related metrics derived from PTT and STAT. Signal quality indices for ECG, PPG, and STAT signals were also computed to assess signal reliability. A temporal convolutional network (TCN) model was designed to capture the complex, non-linear dependencies between these multi-modal features and beat-to-beat BP. &#xD;&#xD;Main results: The approach was rigorously validated using Leave-One-Subject-Out Cross-Validation (LOSOCV) on 29 recordings from ten healthy volunteers undergoing isometric handgrip exercises. The proposed TCN model significantly outperformed traditional PTT and STAT-only baselines, achieving a Mean Absolute Difference (MAD) of 5.58 mmHg for Systolic BP (SBP), 4.39 mmHg for mean BP (MBP) and 4.34 mmHg for diastolic BP (DBP). Notably, the TCN model exhibited significantly lower errors (p < 0.05, Wilcoxon Test) during dynamic BP fluctuations compared to baseline models. &#xD;&#xD;Significance: The study demonstrates that fusing tonometry-derived pressure morphology with hemodynamic timing features effectively mitigates the limitations of conventional PTT methods. This approach offers a robust solution for continuous, calibration-resilient BP estimation. &#xD.

We present a genome assembly from an individual male Aethes tesserana (Downland Conch; Arthropoda; Insecta; Lepidoptera; Tortricidae). The assembly contains two haplotypes with total lengths of 486.12 megabases and 482.92 megabases. Most of haplotype 1 (99.81%) is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.54 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces genomes for eukaryotic species found in Britain and Ireland.

Monolayer and multilayer MoS2are extremely fascinating materials for optoelectronics, particularly in scenarios involving high excitation carrier densities. Consequently, it is essential to understand the various processes and their associated time scales in monolayer and multilayer two-dimensional materials under such high excitation densities. Here, We demonstrate that carrier dynamics in monolayer and multilayer MoS2exhibit distinctly different behaviors above the Mott density, with monolayers showing faster carrier relaxation and enhanced many-body interactions compared to multilayers. Despite the similarity in band structure near theK-point and the formation of A-excitons, pronounced differences in the transient response are observed, highlighting the influence of the overall band structure. Exciton dissociation, bandgap renormalization, and intervalley relaxation play a consequential role in dictating the ultrafast transient properties of these samples. The study in this paper provides a detailed understanding of the fundamental optoelectronic properties of the two-dimensional MoS2at high excitation densities, paving the way for its potential applications in various photonic and optoelectronic domains.

Introduction Large language models (LLMs) are increasingly used for clinical decision support and show high adherence to clinical practice guidelines. However, LLM-generated responses may translate guideline recommendations into definitive clinical advice without adequately reflecting the underlying strength of recommendations or the quality of supporting evidence. This study aimed to evaluate the risk of guideline overselling in GPT-generated responses based on guidelines. Methods Four ESGE colorectal guidelines were selected. All guideline statements were extracted together with their strength of recommendation and the quality of evidence. For each statement, a clinical vignette and related question were submitted to GPT-5 using both generic and guideline-oriented prompts. Three independent experts assessed each response for adherence to guideline content and calibration of wording. Results Overall, GPT-generated responses showed high adherence to guideline content with generic prompts (54/59, 91.5%), whereas calibration to recommendation strength and evidence quality was lower (44/59, 74.6%). Calibration was significantly reduced for weak versus strong recommendations (33.3% vs. 86.4%, P < 0.001) and for statements supported by low-quality versus high- or moderate-quality evidence (44.4% vs. 90.2%, P < 0.001). After prompt calibration experiment, adherence increased to 96.6% (57/59), while calibration markedly improved to 94.9% (56/59), mainly through reduced overly assertive wording for low-certainty recommendations. Conclusions GPT-5 demonstrated high guideline adherence but limited calibration to the quality of evidence underlying individual recommendations, with the potential to amplify the perceived certainty of low-quality evidence. Explicit incorporation of recommendation strength and evidence quality within prompts substantially improves calibration and may mitigate this risk in clinical use.

Pancreatic cancer has very low survival due to late diagnosis. Symptoms are often non-specific, complicating early detection in primary care. The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) algorithm uses weight change, glycaemic control, and age at diabetes onset to identify new-onset diabetes (NOD) patients at increased pancreatic cancer risk. It was developed in the USA and has not been validated in the UK. Aim To validate ENDPAC in a UK primary care population and assess its predictive utility. Design and setting Retrospective cohort study using ORCHID, a national primary care sentinel network. Method Adults aged &#x2265;50 with NOD and requisite glycated haemoglobin (HbA1c) and weight data were included. ENDPAC scores were calculated. Model performance was evaluated via discrimination, calibration, sensitivity, specificity, PPV and NPV. The Youden index identified optimal cutoffs. Sensitivity analyses assessed measurement timing, repeat HbA1c testing and multiple values. Results Among 70,050 individuals, 185 (0.26%) developed pancreatic cancer. Cases were older with higher HbA1c and greater weight loss at diagnosis. ENDPAC achieved an area under the curve (AUC) of 0.733. An optimal cutoff of &#x2265;3 classified 27.6% of individuals as high-risk, with 62.6% sensitivity, 72.3% specificity, 0.6% PPV and 99.9% NPV. Sensitivity analyses showed similar performance across measurement windows and handling of multiple values. ENDPAC shows moderate discrimination in UK primary care. Although it has a relatively low PPV (0.6%), integration into routine systems could provide scalable, low-cost automated risk stratification, identifying people with NOD at higher pancreatic cancer risk as part of a sequential diagnostic pathway.

We present a genome assembly of Astragalus glycyphyllos (Wild Liquorice; Streptophyta; Magnoliopsida; Fabales; Fabaceae). The genome sequence has a total length of 680.28 megabases. Most of the assembly (99.71%) is scaffolded into 8 chromosomal pseudomolecules. The mitochondrial sequences have lengths of 173.12 and 189.37 kilobases and the plastid genome assembly has a length of 124.0 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

The diversity of healthcare systems across Europe has predictably resulted in significant variations in point-of-care ultrasound (PoCUS) training and practice for emergency medicine (EM). To encourage a more synchronized approach and address these inconsistencies, the European Society of Emergency Medicine (EUSEM) chartered its ultrasound section to develop a comprehensive curriculum compendium that should serve as a foundational guide for European Emergency Medicine PoCUS clinical and educational guidelines and policies. Under the leadership of a dedicated task force, the EUSEM ultrasound section developed this compendium to provide a structured, tiered framework designed to meet the needs of physicians at every skill level, from novice to advanced users. The compendium emphasizes applications that are currently practiced in different and diverse emergency departments in Europe, including a broad range of topics. An important goal was allowing flexibility to accommodate the unique resources and challenges of different healthcare environments, so that EM physicians can achieve PoCUS competencies matching their local circumstances and needs. To achieve this goal, good educational and clinical stewardship throughout this process is a key part to the success of advancing PoCUS in European EM. This compendium is intended as a resource for creating standardized yet adaptable training pathways. It represents a major step toward harmonizing and advancing PoCUS practice in European EM. Die Vielfalt der verschiedenen Gesundheitssysteme in Europa hat dazu gef&#xfc;hrt, dass grosse Unterschiede in der Ausbildung und Anwendung des Point-of-Care-Ultraschalls (PoCUS) in der Notfallmedizin bestehen. Um einen st&#xe4;rker synchronisierten Ansatz zu f&#xf6;rdern und diesen Unterschieden zu begegnen, hat die Europ&#xe4;ische Gesellschaft f&#xfc;r Notfallmedizin (EUSEM) ihre Ultraschallsektion damit beauftragt, ein umfassendes Curriculum-Kompendium zu entwickeln. Dieses soll als ein Leitfaden f&#xfc;r Europ&#xe4;ische Richtlinien und Standards f&#xfc;r PoCUS in der klinischen Ausbildung in der Notfallmedizin dienen. Unter der Leitung einer Task Force hat die Ultraschallsektion der EUSEM dieses Kompendium erarbeitet, um Rahmenbedingungen zu schaffen, die den Bed&#xfc;rfnissen von &#xc4;rztinnen und &#xc4;rzten auf jedem Kompetenzniveau - vom Einsteiger bis zum fortgeschrittenen Anwender - gerecht werden. Das Kompendium beinhaltet Ultraschallanwendungen, die in derzeit sehr diversen Notfallstationen in ganz Europa praktiziert werden, und deckt daher ein breites Spektrum PoCUS-Anwendungen in der Notfallmedizin ab. Ein zentrales Ziel dieser Arbeit war es, Flexibilit&#xe4;t zu erm&#xf6;glichen, um die spezifischen Merkmale wie auch Ressourcen der jeweiligen Gesundheitssysteme zu ber&#xfc;cksichtigen, sodass Notfallmediziner:innen PoCUS-Kompetenzen erwerben k&#xf6;nnen, die ihren lokalen Gegebenheiten und Anforderungen entsprechen. Um das Ziel der Weiterentwicklung von PoCUS in der europ&#xe4;ischen Notfallmedizin zu erreichen, ist ein entscheidender Erfolgsfaktor eine gute Begleitung sowohl in der klinischen Anwendung, wie auch in der Ausbildung. Dieses Kompendium soll als Grundlage zur Entwicklung standardisierter, zugleich aber anpassungsf&#xe4;higer Ausbildungspfade dienen. Es stellt einen wichtigen Schritt zur Harmonisierung und Weiterentwicklung des PoCUS in der europ&#xe4;ischen Notfallmedizin dar.

We model the cardiorespiratory interaction as arising within a collection of coupled, non-autonomous, nonlinear oscillators with explicitly time-dependent frequency modulation. The resulting system is analysed in terms of phase tracking and stability using finite-time Lyapunov exponents. We show that synchronisation emerges from the interplay between coupling strength, intrinsic frequency mismatch, and modulation amplitude, giving rise to regimes of stable entrainment, intermittent synchronisation, and desynchronised dynamics. The transitions between these regimes are governed by the system's ability to track time-dependent attractors rather than by fixed phase-locking conditions. Numerical simulations, together with physiological recordings, demonstrate that time-varying modulation and interaction structure are both essential to reproduce observed cardiorespiratory behaviour. In particular, the data indicate that coupling is not stationary but evolves over time, contributing significantly to the observed variability in synchronisation patterns. These results suggest that the cardiorespiratory interaction is more naturally interpreted as an emergent property of a non-autonomous dynamical system with evolving interaction geometry and moving attractors, rather than as a stationary coupling process between autonomous oscillators.

Modelling micro- and meso-scopic scale thermodynamic and transport properties of soft condensed matter hinges upon its representation. This is especially relevant for polar solvents such as water, since these require effective representation of their dielectric nature as driven by molecular charge distributions and molecular network structuring. The dielectric nature of a medium leads to complex phenomena such as local polarisability response and restructuring near interfaces in reaction to changes in local charge distributions. Inclusion of such phenomena when using larger-than-atomistic techniques such as coarse-grained molecular dynamics (CG-MD) and dissipative particle dynamics (DPD) is still an open question, to which we provide a novel way to consider and justify the necessary and suitable coarse-graining level, enabling us to compare new polar CG models' performance against that of an underlying atomistic model. We polarise our previous non-polar \nDPD\ water model to prepare it for use in simulations of liquid electrolytes as well as solvated organic membranes and measure its fitness to serve as a dielectric medium by comparing its properties to those of the TIP3P water model, while simultaneously observing changes to properties already represented well by the non-polar model.

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Mycolic acids are key components of the mycobacterial cell envelope, contributing to its structural integrity and intrinsic resistance to environmental stress. The polyketide synthase Pks13 catalyzes the final Claisen condensation step in mycolic acid biosynthesis and is conserved across Corynebacteriales. While the catalytic cysteine within the ketosynthase (KS) domain is established as essential for activity, the role of surrounding residues in supporting catalysis remains less well understood. Herein, we utilized a Mycobacterium smegmatis conditional pks13 mutant, and subsequent complemented strains harbouring a plasmid-borne copy of pks13 to probe the functional importance of selected residues within the KS domain from previous structural studies. These site-directed mutagenesis studies identified Asp264 as critical for Pks13 function. The D264A strain showed severely impaired growth along with a pronounced loss of mycolate synthesis and mycolate-containing lipids: trehalose dimycolate (TDM) and trehalose monomycolate (TMM). In contrast, other mutations had either little or no significant effect on cell viability or mycolate synthesis or mycolate-containing lipids. Structural modelling of the KS domain suggests that loss of Asp264 disrupts the local active-site environment, resulting in compaction of the binding pocket and altered conformation of a loop proximal to the catalytic residue Cys267. Together, these findings demonstrate that Asp264 is essential for Pks13 function and likely contributes to maintaining the structural environment of the KS domain.

We present a genome assembly from an individual femal Neoascia tenur (hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence has a total length of 491.77 megabases. Most of the assembly (97.23%) is scaffolded into 4 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 16.31 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces genomes for eukaryotic species found in Britain and Ireland.

On the occasion of the Annual National Conference of Indian Psychiatric Society 2025 (ANCIPS 2025), which was held from January 22 to January 25, 2025 with the Theme: "Neurobiology of Illness to Wellness," the organizing committee has prepared the "Hyderabad Declaration on Collaboration for Global Mental Health: From Illness to Wellness." The draft for this declaration has been prepared in consensus with the world leaders of various psychiatric associations belonging to India (IPS), America (APA), Canada (ICPA), and Britain (BIPA). This declaration consists of various key principles. These key principles are made highlighting the shift of the paradigm from illness to wellness, need to empower the health care fraternities, integrating the physical health with mental health, and need for increasing the sensitization and access to mental health and decreasing the stigma on mental health, thus motivating the health fraternities to have a collaborative approach to empower the community with special focus on vulnerable populations including youth and women.

Sodium chloride (NaCl) has been proposed as a retrospective and prospective dosemeter for optically stimulated luminescence (OSL) dosimetry. The potential for NaCl pellets for individualised in situ dose assessment during a radiological or nuclear (R/N) emergency was enhanced by their suitability with a portable OSL reader. The current paper studies the possibility of developing a public dosimetric badge, based on NaCl pellets and commonly available low-cost materials.Copper, aluminium and polylactic acid (PLA) were tested for reducing the overresponse to low X-ray energies, and the results indicated that copper is the best candidate-material for filtering purposes. Furthermore, the ratio between filtered and unfiltered samples may potentially be used to determine the mean energy of the exposure field in some circumstances. In addition, the NaCl pellets exhibit constant response for air kerma rates between 0.006 to 1.9 Gy/min. The fading of the pellets does not present any energy dependence. Air kerma reconstruction with three stimulation modes was investigated, and the reconstructed air kerma deviated from the nominal value between 0.8 and 7.9%, which were within measurement uncertainties.The discrepancy between Monte Carlo simulations of the exposed pellets and the experimental data is possibly due to the intrinsic luminescent efficiency of the salt, which in the current study is assumed constant for the entire energy regime.Alanine, exposed together with the NaCl pellets, was studied for the intercomparison and air kerma rate experiments, and showed accurate air kerma reconstruction, with deviation from the actual doses within ~1&#x3c3;, and no significant variation with the air kerma rate. Analysis of the alanine dose estimations investigated the conventional peakto-peak method alongside a fitting method, which did not lead to any improvements in measurement accuracy.

New adult tuberculosis (TB) vaccines are in clinical trials and may be licensed as soon as 2028. However, vaccine rollout requires addressing multiple contextual factors beyond clinical trial findings. This study explored stakeholders' perspectives on the introduction of a new TB vaccine in Indonesia. We used a mixed-methods approach combining a stakeholder consultation in Jakarta (13/03/2025) among 28 participants with diverse expertise and follow-up interviews with two of those participants. Participants completed a structured questionnaire (via Slido) consisting of closed- and open-ended questions, adapted into Bahasa. Questions explored factors to be considered regarding vaccine introduction, target populations, delivery strategies, regulatory considerations, and lessons from other vaccine programs. Quantitative data were analysed descriptively, and qualitative responses underwent thematic analysis. All participants agreed on the importance of TB vaccine introduction. Key concerns were minimum efficacy of 50% and comparative effectiveness against other interventions, such as TB preventive treatment. Most agreed that vaccine introduction should not depend on local manufacturing capacity, administration route, or dosage. Critical enablers identified were adequate funding, strong political commitment, and demand generation through public acceptance. Priority target populations included people living with HIV/AIDS, individuals with diabetes, household contacts of TB patients, adolescents, and healthcare workers. Major challenges highlighted were vaccine hesitancy, halal issues, misinformation, and limited healthcare worker knowledge. Opinions diverged regarding the feasibility of vaccine rollout without Interferon-Gamma Release Assay (IGRA) testing: nine opposed vaccinating those with IGRA-negative status, six abstained, and three argued that IGRA-testing was unnecessary and cost-inefficient due to its high price. Regulatory and budgeting processes were cited as additional barriers. Introducing new TB vaccines in Indonesia will be complex and concerns extend beyond efficacy. Its success will depend on coordinated strategies to define target populations, design tailored delivery approaches, address vaccine hesitancy, and navigate regulatory and financing challenges.