bluuebunny/crossref_metadata_2025_split huggingface dataset:
The international trial of nasal oxygen therapy after cardiac surgery (NOTACS) in patients at high risk of postoperative pulmonary complications: Economic evaluation protocol and analysis plan
Authors: Shetty Siddesh , Duckworth Melissa , Norman Richard , Affandi Jacquita , Dawson Sarah , Fox-Rushby Julia 
Published: October 2024

AbstractIntroductionHigh-Flow Nasal Therapy (HFNT) is an innovative non-invasive form of respiratory support. Compared to standard oxygen therapy (SOT), there is an equipoise regarding the effect of HFNT on patient-centred outcomes among those at high risk of developing postoperative pulmonary complications after undergoing cardiac surgery. The NOTACS trial aims to determine the clinical and cost-effectiveness of HFNT compared to SOT within 90 days of surgery in the United Kingdom, Australia, and New Zealand. This protocol describes the methods and analyses planned for economic evaluation embedded within the ongoing NOTACS trial.Methods and analysisThe economic evaluation will identify, measure and value resources and health outcomes in both trial arms and compare changes in costs with ‘days alive and at home’ and EQ-5D-5L quality adjusted life years (QALYs) from the perspective most relevant to the decision-making country. Results from pooling data across the trial will use health and social care sector perspective. All patient-specific data including hospital/community care and health outcomes will be collected prospectively. Unit costs will be sourced interpreted using recommended national cost-effectiveness thresholds.Registration detailsThe study is registered with ISRCTN (ISRCTN14092678) on 13/05/2020. ISRCTN is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set.
Determining the indirect costs of suicide in Sweden between 2010 and 2019 - A cost of illness study
Authors: Wikström Daniela , Nystrand Camilla , Hadlaczky Gergö , Gedin Filip 
Published: October 2024

AbstractBackgroundGlobally, more than 700 thousand people commit suicide annually. In Sweden, the yearly incidence is between 1000 and 1500 people, which is higher than the global average. Understanding the economic burden of suicide could help highlight the importance and urgency of finding more effective treatments and preventative measures to help people suffering from suicidal thoughts and support studies evaluating the cost-effectiveness of various interventions.MethodThis national population-based cross-sectional study estimated the indirect costs associated with all suicides in Sweden between 2010 and 2019. Indirect costs were estimated using the human capital approach. Data regarding average salaries and employment rates were extracted from publicly available data in Sweden. Productivity loss was estimated over two time horizons, the year following the suicide and over a lifetime horizon. Estimations were performed in total numbers for the yearly cohorts as well as per person.ResultsBetween 2010 and 2019, 1 406 to 1 591 suicides occurred every year in Sweden. In total, approximately 26 500 productive life years are lost every year due to suicide. In 2019, the productivity loss due to all suicides in Sweden was estimated to be 44 million euros over a one-year time horizon, where 10 million euros are direct losses in local and regional authority taxes. Over a lifetime, productivity losses amounted to 935 million euros. The corresponding estimations per person were 37 and 778 thousand euros respectively over a one-year and a lifetime time horizon Over a one-year time horizon, the productivity loss was highest in the older age groups.ConclusionsThis study provides valuable insights into the economic burden of suicide on Swedish society. It underlines the potential economic benefits of effective suicide prevention, aligning with previous research highlighting the substantial returns—both monetary and in terms of human well-being—that successful prevention strategies can yield.
Novel and optimized mouse behavior enabled by fully autonomous HABITS: Home-cage Assisted Behavioral Innovation and Testing System
Authors: Yu Bowen , Li Penghai , Xu Haoze , Wang Yueming , Xu Kedi , Hao Yaoyao 
Published: October 2024

AbstractMice are among the most prevalent animal models used in neuroscience, benefiting from the extensive physiological, imaging and genetic tools available to study their brain. However, the development of novel and optimized behavioral paradigms for mice has been laborious and inconsistent, impeding the investigation of complex cognitions. Here, we present a home-cage assisted mouse behavioral innovation and testing system (HABITS), enabling free-moving mice to learn challenging cognitive behaviors in their home-cage without any human involvement. Supported by the general programming framework, we have not only replicated established paradigms in current neuroscience research but also developed novel paradigms previously unexplored in mice, resulting in more than 300 mice demonstrated in various cognition functions. Most significantly, HABITS incorporates a machine-teaching algorithm, which comprehensively optimized the presentation of stimuli and modalities for trials, leading to more efficient training and higher-quality behavioral outcomes. To our knowledge, this is the first instance where mouse behavior has been systematically optimized by an algorithmic approach. Altogether, our results open a new avenue for mouse behavioral innovation and optimization, which directly facilitates investigation of neural circuits for novel cognitions with mice.
A patient-centric knowledge graph approach to prioritize mutants for selective anti-cancer targeting
Authors: Gorostiola González Marina , IJzerman Adriaan P. , van Westen Gerard J.P. 
Published: October 2024

AbstractPersonalized oncology has revolutionized cancer treatment by targeting specific genetic aberrations in tumors. However, the identification of suitable targets for anti-cancer therapies remains a challenge. In this study, we introduce a knowledge graph approach to prioritize cancer mutations with clinical, functional, and structural significance as potential therapeutic targets. Focusing on the human kinome, we integrate protein-protein interaction and patient-centric mutation networks to construct a comprehensive network enriched with transcriptomic, structural, and drug response data, together covering five layers of information. Moreover, we make the constructed knowledge graph publicly available, along with a plethora of scripts to facilitate further annotation and expansion of the network. Interactive visualization resources are also provided, ensuring accessibility for researchers regardless of computational expertise and enabling detailed analysis by cancer type and individual layers of information. This comprehensive resource has the potential to identify relevant mutations for targeted therapeutic interventions, thereby advancing personalized oncology and improving patient outcomes.
Patterns of leaf, flower and fruit phenology and environmental relationships in a seasonal tropical forest in the Indian Eastern Himalaya
Authors: Datta Aparajita , Banerjee Soumya , Naniwadekar Rohit , Thapa Khem , Rathore Akanksha , Thapa Kumar , Brah Turuk , Nabum Tali , Shukla Ushma , Sidhu Swati , Borawake Noopur 
Published: October 2024

ABSTRACTTree phenology plays an important role in determining the structure and function of tropical forest communities. However, there are few long-term studies on tree phenology from South Asia. We monitored 716 trees of 54 species monthly from 2011 to 2023 for leaf flush, flowering, and fruiting in Pakke Tiger Reserve, Arunachal Pradesh, India. We examined monthly patterns in the percentage of species and trees in leaf flush, flower and fruit and characterized phenological seasonality using circular statistics. Flowering periodicity was classified using Fourier analysis and we examined the relationships between phenological activity and temperature, rainfall, solar radiation and daylength using GAMLSS. Leaf flush and flowering were moderately seasonal, peaking in the warm dry season months of March to May. Fruiting patterns and their seasonality differed among dispersal modes. At the community level and for bird-dispersed species, fruiting was bimodal and relatively aseasonal, peaking in April and October. The highly seasonal fruiting of mammal-dispersed species peaked in October, while that of mechanically-dispersed species was bimodal and concentrated in the dry season months. The majority of species (78.13%) and trees (51.17%) flowered annually. Daylength, solar radiation and minimum temperature had significant nonlinear effects on phenology. This indicated the existence of narrow ranges of optimal climatic conditions for phenology, which could be affected by climate change. Our study emphasizes the need for long-term monitoring to rigorously quantify phenological patterns, particularly in the context of rapid global change.
Glycogen phosphorylase from the methanogenic archaeonMethanococcus maripaludis: Unique regulatory properties of a pyridoxal 5’-phosphate independent phosphorylase
Authors: González-Ordenes Felipe , Herrera-Soto Nicolas , Hernández-Cabello Leslie , Bustamante Catalina , Vallejos-Baccelliere Gabriel , Castro-Fernandez Victor , Guixé Victoria 
Published: October 2024

AbstractGlycogen phosphorylase (GP) is a critical enzyme in glycogen metabolism. Even though methanogens from the archaeal ordersMethanosarcinalesandMethanococcalesare unable to grow on sugars, they store glycogen, which is metabolized through the glycogenolysis and glycolytic pathways when the carbon source for methanogenesis is depleted. Under these metabolic conditions, the activity of the GP enzyme is essential. To be active, all phosphorylases characterized to date require the cofactor pyridoxal 5’-phosphate (PLP). This cofactor is covalently bound via Schiff base to a strictly conserved lysine residue at the active site. Extensive GP sequence analysis of organisms from different domains of life shows strict conservation of active site residues despite significant differences in sequence length. Interestingly, in GP sequences of organisms from the orderMethanococcalesof archaea, a threonine residue replaces the conserved lysine involved in PLP binding. The purification and characterization of recombinant GP fromMethanococcus maripaludisshow that the enzyme exhibits glycogen phosphorylase activity and high specificity for glycogen as a substrate. Analysis of the PLP content performed by several methods, such as absorbance, fluorescence, cyanohydrin adduct formation, and mass spectrometry, confirmed the absence of PLP. The results demonstrate that an archaeal GP from the orderMethanococcalesperforms catalysis without the PLP cofactor, deviating from the well-established phosphorylase catalytic mechanism and revealing new scenarios for the glucosyltransferase reaction. Moreover, analysis of enzyme regulation shows that the activity is affected by various molecules, including nucleotides, intermediates of carbon metabolism, and phosphate species. Most of these molecules have not previously been identified as regulators of glycogen phosphorylases in prokaryotes. These results suggest that other GPs fromMethanococcalescan undergo complex regulation.
Investigation of the effect of physiological factors on resting-state and task-based functional connectivity
Authors: Askarinejad S. Emad , Poline Jean-Baptiste , Mitsis Georgios D. 
Published: October 2024

AbstractUnderstanding the brain’s functional network through functional connectivity (FC) is crucial for gaining deeper insights into brain functional mechanism and identifying a potential biomarker for diagnosing neurological disorders. Despite the development of various FC measures, their reliability under different conditions remains under-explored. Moreover, physiological noise can obscure true neural activity, and accordingly, introduce errors into FC patterns. This issue necessitates further investigation. In this study, we evaluate and compare the performance of various methods using Local Field Potential and Blood-Oxygen-Level-Dependent signals across different conditions. We also examine the impact of physiological artifacts on BOLD-FC results. Our comprehensive assessment covers multiple modalities of brain signals, diverse task paradigms, and varying noise levels. Our findings reveal that while Granger Causality-based methods exhibit significant limitations, particularly with BOLD data, multivariate techniques (e.g. partial correlation) demonstrate greater robustness in distinguishing between different types of connections within the network. Notably, our results indicate that physiological artifacts substantially affect FC values, leading to erroneous connectivity estimates, especially with bivariate methods. This research offers a foundational analysis of the effects of physiological artifacts on FC results and provides valuable insights for future studies.
Characterization of newly isolated bacteriophages targeting carbapenem-resistantKlebsiella pneumoniae
Authors: Kim Bokyung , Kim Shukho , Choi Yoon-Jung , Shin Minsang , Kim Jungmin 
Published: October 2024

AbstractKlebsiella pneumoniae, a Gram-negative opportunistic pathogen, is increasingly resistant to carbapenems in clinical settings. This growing problem necessitates the development of alternative antibiotics, with phage therapy being one promising option. In this study, we investigated novel phages targeting carbapenem-resistantKlebsiella pneumoniae(CRKP) and evaluated their lytic capacity against clinical isolates of CRKP. First, 23 CRKP clinical isolates were characterized using Multi-locus Sequence Typing (MLST), carbapenemase test, string test, and capsule typing. MLST classified the 23K. pneumoniaeisolates into 10 sequence types (STs), with the capsule types divided into nine known and one unknown type. From sewage samples collected from a tertiary hospital, 38 phages were isolated. Phenotypic and genotypic characterization of these phages was performed using Random Amplification of Polymorphic DNA-PCR (RAPD-PCR), transmission electron microscopy (TEM), and whole genome sequencing (WGS) analysis. Host spectrum analysis revealed that each phage selectively lysed strains sharing the same STs as their hosts, indicating ST-specific activity. These phages were subtyped based on their host spectrum and RAPD-PCR, identifying nine and five groups, respectively. Fourteen phages were selected for further analysis using TEM and WGS, revealing 13Myovirusesand onePodovirus. Genomic analysis grouped the phages into three clusters: one closely related toAlcyoneusvirus, one toAutographiviridae, and others toStraboviridae. Our results showed that the host spectrum ofK. pneumoniae-specific phages corresponds to the STs of the host strain. These 14 novel phages also hold promise as valuable resources for phage therapy against CRKP.
Acceptability and implementation considerations of the patient-collected rectal swab for sexually transmitted infections testing among men who have sex with men and transgender women in Kigali, Rwanda
Authors: Twahirwa Rwema Jean Olivier , Okonkwo Nneoma E. , Hamill Matthew M. , Lyons Carrie E. , Prata Menezes Neia , Makuza Jean Damascene , Nyombayire Julien , Rwibasira Gallican Nshogoza , Kagaba Aflodis , Sullivan Patrick , Allen Susan , Karita Etienne , Baral Stefan D. 
Published: October 2024

BackgroundRectal sexually transmitted infections (STI) are prevalent among men who have sex with men (MSM) and transgender women (TGW). Self-collection of rectal specimens is widely used globally, but limited data exist on its implementation in Africa. We report experiences of MSM/TGW self-collecting rectal STI specimens in Kigali.MethodsFrom March to August 2018, 738 MSM/TGW were recruited in a cross-sectional study using respondent-driven sampling in Kigali. We tested forNeisseria gonorrheaandChlamydia trachomatisusing the Cepheid GeneXpert CT/NG platform on self-collected rectal swabs. Likert scales assessed self-collection difficulty and comfort. Ordered logistic regression analyses were performed to characterize factors associated with self-collection difficulty.ResultsOverall, 14%(106) identified as TGW. In total, 78%(577) found rectal swab self-collection easy/very easy, while 15%(108) found it difficult/very difficult. Most, 92%(679), were comfortable/very comfortable with the test, and 98%(730) said they would repeat the test in the future. In multivariable RDS-adjusted analyses, discomfort with the swab was positively associated with difficulty in self-collection (adjusted cumulative odds ratios ((aCOR): 7.9(95%CI: 4.9-12.8)) and having a prevalent rectal STI (aCOR: 4.19, 95%CI: 2.02-8.72) was significantly associated with difficulty.Furthermore, 10%(75) of rectal swabs returned indeterminate results (65 invalid results and 10 errors).ConclusionMost MSM/TGW found self-collection of rectal swabs easy, comfortable, and collected valid samples. Self-collection of rectal swabs could be used alongside clinic- and community-based STI testing to improve diagnosis and treatment in Rwanda. However, measures to optimize sample collection and processing are needed to reduce the cost and clinical implications of indeterminate results
I answer to clinical scenarios as a real doctor because I “Think”: “ChatGPTo1” new reasoning ability
Authors: Mondillo Gianluca , Colosimo Simone , Perrotta Alessandra , Frattolillo Vittoria , Masino Mariapia , Marzuillo Pierluigi 
Published: October 2024

AbstractThe adoption of the ChatGPT o1 model represents a significant advancement in the management of clinical cases due to the introduction of a new structured reasoning capability, the “chain-of-thought reasoning” (CoT). In this study, 350 general medicine clinical cases were tested using ChatGPT o1 and ChatGPT o1 mini, and their performance was compared with ChatGPT 4o and ChatGPT 4o mini to evaluate diagnostic accuracy. The results showed that ChatGPT o1 achieved a correct answer rate of 93.4%, outperforming both ChatGPT 4o (82.2%) and the mini versions (ChatGPT o1 mini: 70.2% and ChatGPT 4o mini: 66.2%). The CoT technique enabled the model to provide more coherent and transparent responses, reducing the occurrence of so-called “hallucinations.” This study highlights how the ChatGPT o1 model can be a valuable tool in clinical practice, although its use requires supervision to ensure patient safety, especially in critical settings.
Identification of novel nutrient sensitive human yolk sac functions required for embryogenesis
Authors: White M , Arif-Pardy J , Bloise E , Connor KL 
Published: October 2024

AbstractThe human yolk sac (hYS) is essential for embryo nutrient biosynthesis/transport and development. However, there lacks a comprehensive study of hYS nutrient-gene interactions. Here we performed a secondary analysis of hYS transcript profiles (n=9 samples) to identify nutrient-sensitive hYS genes and regulatory networks, including those that associate with adverse perinatal phenotypes with embryonic origins. Overall, 14.8% highly expressed hYS genes are nutrient-sensitive; the most common nutrient cofactors for hYS genes are metals and B-vitamins. Functional analysis of highly expressed hYS genes reveals that nutrient-sensitive hYS genes are more likely to be involved in metabolic functions than hYS genes that are not nutrient-sensitive. Through nutrient-sensitive gene network analysis, we find that four nutrient-sensitive transcription regulators in the hYS (with zinc and/or magnesium cofactors) are predicted to collectively regulate 30.9% of highly expressed hYS genes. Lastly, we identify 117 nutrient-sensitive hYS genes that associate with an adverse perinatal outcome with embryonic origins. Among these, the greatest number of nutrient-sensitive hYS genes are linked to congenital heart defects (n=54 genes), followed by microcephaly (n=37). Collectively, our study characterises nutrient-sensitive hYS functions and improves understanding of the ways in which nutrient-gene interactions in the hYS may influence both typical and pathological development.
Feasibility of an App-Assisted and Home-Based Video Version of the Timed up and Go Test for Patients with Parkinson Disease: vTUG
Authors: Grobe-Einsler Marcus , Gerdes Anna , Feige Tim , Maas Vivian , Matthews Clare , García Alejandro Mendoza , Fages Laia Comas , Davies Elin Haf , Klockether Thomas , Falkenburger Björn H. 
Published: October 2024

AbstractBackgroundParkinson Disease (PD) is a progressive neurological disorder. Current therapeutic trials investigate treatments that can potentially modify the disease course. Testing their efficiency requires frequent and precise clinical outcome assessments (COA) of symptoms that remain problematic under symptomatic treatments, such as gait and balance. Home-based examinations may enhance patient compliance and, in addition, produce more reliable results by assessing patients more regularly in their familiar surroundings.ObjectiveThe objective of this study was to assess the feasibility of a digitized COA designed to video record the Timed up and Go (vTUG) test at home via a study-specific smartphone app for patients with PD.MethodIn this study, 28 patients were recruited and asked to perform at home each week a set of three consecutive vTUG tests over a period of 12 weeks using an app. The videos were subjected to a manual review to ascertain the durations of the individual vTUG phases, as well as to identify any errors or deviations in the setup that might have influenced the result. To evaluate the usability and user-friendliness of the vTUG and app, the System Usability Scale (SUS) and User Experience Questionnaire (UEQ) were administered to patients at the study end.ResultsOverall, 19 patients completed the 12-week study, 17 of which recorded 10 videos or more. A total of 706 vTUGs with complete timings were recorded. Random Forest Regression yielded “time to walk up” as the most important segment of the vTUG for predicting the total time. Variance of vTUG total time was significantly higher between weeks than it was between the three consecutive vTUGs at one time point [F(254,23) = 6.50, p < 0.001]. The correlation between vTUG total time and UPDRS III total score was weak (r = 0.24). Yet, correlation between vTUG and a derived gait subscore (UPDRS III items 9-13) was strong (r = .59). A linear mixed-effects model revealed a significant effect of patient-reported motion status on vTUG total time. Including additional variables such as UPDRS III gait subscore, different footwear, and chairs used, further improved the model fit.ConclusionAssessment of gait and balance by home-based vTUG is feasible. Factors influencing the read-out were identified and could be controlled for future use and longitudinal trials.