bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and functional characterization of p.Lys322stop variant in the SERPINC1 gene causing severe thrombophilia
Authors: Zhang Haiyue , Yue Xinyang , Dai Tenglong , Wu Jun 
Published: December 2024

Abstract
Background
Identification of mutations in the SERPINC1 has illuminated the intricate pathways underlying antithrombin (AT) deficiency. Our group identified a variation in the SERPINC1 gene (c.964 A > T, p.Lys322stop) and further investigated the mechanism of this variant causing AT deficiency.

Methods
Multiple in silico tools were utilized to predict the conservation of mutations and their impact on the AT structure. The coagulation state was evaluated using the thrombin generation assay. Recombinant AT was overexpressed in HEK293T cells. Intracellular kinetics and extracellular secretion of recombinant AT-K322* were scrutinized by RT-qPCR, Western blotting, ELISA, and immunocytofluorescence.

Results
Analysis of conservation in silico indicated 43 out of the 143 amino acids deleted byAT-K322* in AT were highly conserved across homologous species. In vitro expression experiments showed that there was no significant difference in mRNA levels between the mutant (AT-K322*) and wild-type (AT-WT) forms of the protein. The truncated AT-K322* protein was clearly detected in cell lysates, but not in the culture medium.

Conclusion
AT-K322* resulted in the generation of a truncated protein, which in turn affected the secretion of AT, ultimately leading to AT deficiency.
Utilizing machine learning-based QSAR model to overcome standalone consensus docking limitation in beta-lactamase inhibitors screening: a proof-of-concept study
Authors: Pitakbut Thanet , Munkert Jennifer , Xi Wenhui , Wei Yanjie , Fuhrmann Gregor 
Published: December 2024

AbstractIn virtual drug screening, consensus docking is a standard in-silico approach consisting of a combined result from optimized docking experiments, a minimum of two results combination. Therefore, consensus docking is subjected to a lower success rate than the best docking method due to its mathematical nature, an unavoidable limitation. This study aims to overcome this drawback via random forest, an ensemble machine learning model. First, in vitro beta-lactamase inhibitory screening was performed using an in-house chemical library. The in vitro results were later used as a validation. Consequently, we optimized docking protocols for AutoDock Vina and DOCK6 programs. With an appropriate scoring function, we found that DOCK6 could identify up to 70% of all active molecules, double the inappropriate. Further consensus analysis reduced the success rate to 50%. Simultaneously, a false positive rate was down to 16%, which was experimentally favorable for a drug search. Finally, we trained two quantitative structure-activity relationship (QSAR) models using logistic regression as a reference model and a random forest as a test model. After combining consensus docking results, random forest-based QSAR outperformed a logistic regression by restoring the success rate to 70% and maintaining a low false positive rate of around 21%. In conclusion, this study demonstrated the benefit of using a random forest (machine learning)-based QSAR model to overcome a standard consensus docking limitation in beta-lactamase inhibitor search as a proof-of-concept.
The genetic diversity of Strongyloides papillosus in Pakistani goats revealed by whole genome sequencing
Authors: Afshan Kiran , Liu Yuchen , Viney Mark 
Published: December 2024

Abstract
Background
Strongyloides nematodes are livestock parasites, and Strongyloides papillosus infecting ruminant livestock can cause disease. Recent genomic analysis of several Strongyloides species is now facilitating population genomic analyses of natural Strongyloides infections, for example finding that Strongyloides ratti in wild UK rats exists as an assemblage of long-lived, asexual lineages.

Methods
Here we have initiated an investigation into the population genomics of S. papillosus in goats in Pakistan. We sampled Strongyloides from goat faeces and then whole genome sequenced individual larvae.

Results
We find that S. papillosus is common, with a prevalence of 28%; that the population is genetically diverse and that individual goats commonly have mixed-genotype infections, and that there is evidence of admixture in only ca. 20% of worms.

Conclusions
These results now provoke further questions about the host range of different S. papillosus genotypes that can be investigated by further population genomic analyses in the future.

Graphical Abstract
Mapping the dynamics of learning communities about Dutch healthy weight approaches: a causal loop diagram
Authors: ter Bogt Maud J. J. , Bevelander Kirsten E. , Kramer Esther A. H. , van der Wal Merel M. , Molleman Gerard R. M. , van den Muijsenbergh Maria , Fransen Gerdine A. J. 
Published: December 2024

Abstract
Background
Learning communities (LCs) are increasingly used among multidisciplinary public health challenges, such as local healthy weight approaches. LCs aim to stimulate learning, collaboration and actions. Previous research has provided insights into the underlying elements of multidisciplinary LCs, but little is known about the perceived causalities of these elements. Therefore, limited is known about what can be done to leverage LCs. This study aims to gain insights into the perceived dynamics of multidisciplinary LCs during the starting phase, including variables, and interconnectedness between variables.

Methods
To elucidate LC dynamics, all members of two separate LCs participated in a qualitative interview about experiences, perceived learning, and actions during the first six months. Interviews were analyzed thematically. Subsequently, a qualitative causal loop diagram was designed.

Results
The qualitative causal loop diagram showed three intertwined themes. The first theme explains why group dynamics are essential, and how jointly arranging the LC may optimize group dynamics. The second theme explains how insights are obtained through multidisciplinary knowledge exchange. The third theme explains how actions are executed when conditions are met. These LC group dynamics, learning and action influenced one another.

Conclusions
To optimize LCs, it is highly recommended that stakeholders arrange them jointly, involve the appropriate partners, match with LC members’ needs, and motivate members to execute action. LC facilitators are recommended to use the causal loop diagram to identify their bottlenecks and how to intervene in those to optimize the LC.
Supervisor-postgraduate relationship and perceived stress: the mediating role of self-efficacy and the moderating role of psychological resilience
Authors: Liu Shen , Wang Xuquan , Teng Han , Gao Wenxiao , Wang Jing , Xu Fan , Song Minghua , Yang Luna 
Published: December 2024

Abstract
Background
Postgraduate studies often entail significant stress, which can profoundly affect students’ well-being and academic performance. The supervisor-postgraduate relationship plays a pivotal role in shaping stress levels among postgraduate students. This study investigates the mediating role of self-efficacy and the moderating influence of psychological resilience in the link between supervisor-postgraduate relationships and perceived stress in postgraduate students.

Methods
This study employed a cross-sectional research design, conducting a survey among 609 postgraduate students selected through random sampling. The participants, aged between 20 and 53 years (M = 25.14, SD = 3.63), included 265 males and 344 females from various academic stages. Data were collected using validated scales to measure the supervisor-postgraduate relationship, perceived stress, self-efficacy, and psychological resilience. The moderated mediation model analysis was conducted to examine the hypothesized relationships and effects, utilizing SPSS with Hayes’ PROCESS macro to validate the statistical interactions.

Results
The results indicated a significant negative association between the supervisor-postgraduate relationship and perceived stress (β=–0.27, p < 0.01), with self-efficacy partially mediating this relationship (β=–0.14, p < 0.01). Additionally, psychological resilience moderated both the direct effect of the supervisor-postgraduate relationship on perceived stress and the indirect effect via self-efficacy (interaction effect β=–0.10, p < 0.01). These findings underscore the roles of self-efficacy and psychological resilience in reducing stress among postgraduate students, highlighting the importance of supportive supervisory relationships.

Conclusions
These findings underscore the critical importance of supportive supervisor-postgraduate relationships and highlight the roles of self-efficacy and resilience in alleviating stress among postgraduate students. This study offers valuable insights for cultivating positive supervisor-postgraduate relationships and enhancing well-being within postgraduate education.
Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study
Authors: Meng Qiuming , Seto Fumiko , Totsu Tokie , Miyashita Tomoyuki , Wu Songfei , Bougaki Masahiko , Ushio Michiko , Hiruma Takahiro , Trapnell Bruce C. , Uchida Kanji 
Published: December 2024

Abstract
Background
Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time-course immune reprogramming after sepsis was evaluated to explore whether the host is immunocompromised. Leukocyte kinetics in the lung tissue were evaluated in a male C57/BL6 mouse model of mild peritoneal sepsis induced by cecal ligation and puncture, with the survival rate exceeds 90%. Lung immune reactivity was evaluated by intratracheal instillation of lipopolysaccharide (LPS; 30 µg). Furthermore, the effect of interferon (IFN)-β in vivo and ex vivo was evaluated.

Results
Four days after sepsis, the lung water content remained high, even among mice in clinical recovery. While monocytes and neutrophils gradually accumulated in the lung interstitium, the inflammatory cytokine/chemokine expression levels in the lungs continued to decline. Intratracheal LPS instillation induced more leukocyte trafficking and protein leakage into the alveoli in the septic lung, indicating more severe lung injury. However, LPS stimulation-associated mRNA expression of tnf, il6, ccl2, and cxcl1 was suppressed. Intra-alveolar expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and keratinocyte-derived cytokine (KC) was also suppressed. Monocytes isolated from the lung tissue showed an impaired response in il6, ccl2, and cxcl1 to LPS. Systemic IFN-β restored the above impaired regulator function of monocytes, as did coculturing these cells from lung tissue with IFN-β.

Conclusions
Histologically accelerated inflammation and paradoxically suppressed immunological regulator signaling were observed in the early recovery phase of sepsis. This observation may provide a model for the immunologically irresponsive state that occurs in some patients with sepsis. Systemic IFN-β partly restored the post-septic immunocompromised state, indicating its therapeutic potential for the immunosuppressive state seen in some patients with sepsis/ARDS.
Sleeping Beauty? A Prospective Study on the Prevalence of Sleep Problems and Their Potential Determinants in Professional Dancers
Authors: Junge Astrid , van Rijn Rogier M. , Stubbe Janine H. , Hauschild Anja 
Published: December 2024

Abstract
Background
Sleep is important for health and performance but has rarely been studied in professional dancers. The aim was to analyse the prevalence of sleep problems in professional dancers and their potential determinants at the beginning of and during the season.

Methods
Professional dancers of six German companies answered a comprehensive baseline questionnaire on physical and mental health, including the Sleep Difficulty Score of the Athletic Sleep Screening questionnaire (ASSQ-SDS) in the beginning of the season and weekly health reports during the season. Numerical rating scales were used for severity of poor sleep, musculoskeletal pain, being stressed/overloaded, all health problems, impaired ability to dance, and workload in the previous seven days.

Results
Of the 147 dancers who answered the baseline questionnaire, 104 (70.7%) completed in total 3186 weekly health reports (response rate: 71.2%). In the beginning of the season 53% of the dancers reported sleep problems of mild (34.0%), moderate (13.6%) or severe extent (5.4%), without differences between sexes, age groups, ranks of the dancers, company sizes or dance styles. The average weekly prevalence of “poor sleep” during the season was 68.8%. Multivariate regression analyses showed that symptoms of depression were significant determinants of sleep problems and the rating of “poor sleep” at baseline; while musculoskeletal pain, being stresses/overloaded, all health problems, impaired ability to dance, and physical and mental workload were significant determinants of “poor sleep” during the season. Variables of the baseline questionnaire were not significantly related to the individual mean rating of “poor sleep” during the season, except of the quality and duration of sleep.

Conclusion
Sleep problems are frequent in professional dancers and related to their physical and mental health and workload. An assessment of sleep should be part of routine health screenings and interventions to improve sleep should be implemented, especially for dancers with pre-existing sleep problems and for periods of high workload.
Heterogeneity of the rearing environment enhances diversity of microbial communities in intensive farming
Authors: Ashrafi Roghaieh , Sundberg Lotta-Riina , Hyvärinen Pekka , Karvonen Anssi 
Published: December 2024

AbstractHeterogeneity of the rearing environment in farmed animals can improve welfare and stocking success by enhancing natural behaviours, reducing stress, and decreasing pathogen occurrence. Although microbial diversity is often associated with well-being, their direct and indirect effects on health of farmed animals remain underexplored. We examined the impact of structural heterogeneity of aquaculture tanks on microbial communities in tank biofilm and fish gut microbiome. Enrichment (stones and shelters) significantly promoted microbial diversity and community homogeneity in tank biofilm. However, diversity of gut microbiome did not depend on rearing treatment or microbial composition of the environment. Fish in enriched tanks exhibited greater compositional variation in gut microbiome than those in standard tanks. Tanks without enrichments had higher occurrence of potentially pathogenic bacterial families (Corynebacteriaceae and Staphylococcaceae), while enriched tanks had more beneficial gut microbes (Lactobacillus). Microbial diversity in tank biofilm was negatively associated with fish mortality during a natural epidemic of Flavobacterium columnare, suggesting a protective effect of diverse microbial communities. These findings support environmental enrichment in mitigating disease outbreaks through enhanced microbial diversity, providing important implications for disease control and sustainable health management in aquaculture.
Multi-parametric high resolution ultrasound assessment of tibial nerve in diabetic peripheral neuropathy
Authors: Elsayed Walaa Galal , Settein Magdy , Abd Elkhalek Ahmed Mohamed , Albehairy Ahmed , Tharwat Nehal 
Published: December 2024

Abstract
Background
Diabetic peripheral neuropathy (DPN) is a common and serious complication of diabetes occurring in about 50% of patients. It serves as a strong risk factor for disabling pain, foot ulcers and amputation that have a negative effect on the life quality and bring a heavy economic burden. Therefore, it is important to early diagnose DPN for taking influential targeted measures and preventing foot ulcers and amputations. The aim of this study was to assess the role of different high resolution ultrasound (HRUS) parameters in diagnosing DPN.

Results
This study included 60 participants classified into three groups [20 diabetic cases with DPN, 20 diabetic cases without peripheral neuropathy (PN) and 20 age-/sex-matched healthy control]. All cases underwent full clinical and laboratory investigations. HRUS examination including shear wave elastography (SWE) of the tibial nerve was also performed. Our study revealed statistically significant difference as regard maximum thickness nerve fascicles (MTNF) between DPN and control groups (P = 0.005) with a cutoff value of 0.45 mm yielding 85% sensitivity and 75% specificity. As regard nerve cross-sectional area (CSA), there was significant statistical difference between each of the three studied groups. A cutoff value of 17.5 mm2 was excellent in differentiating DPN group from control group with 80% sensitivity and 95% specificity. The highest mean nerve stiffness was noted among DPN group compared to diabetics without PN and control groups with significant statistical difference between each of the studied groups. The mean nerve stiffness was excellent in differentiating DPN group from control group with 100% sensitivity and 100% specificity. There was significant statistical positive correlation between neuropathy disability score and diabetes duration, HbA1c levels, MTNF, nerve CSA and stiffness.

Conclusions
Multi-parametric HRUS using MTNF, CSA and SWE is a promising quantitative technique that has an excellent additive value to the usual qualitative nerve examination. High image quality, real-time examination, non-invasiveness, low cost, wide availability and multi-parametric assessment make HRUS superior to nerve conduction test. It can serve as an accurate novel technique for screening and early diagnosis of DPN even with normal clinical and nerve conduction studies.
Economies Before Scale: I.T. Strategy and Performance Dynamics of Young U.S. Businesses
Authors: Jin Wang , McElheran Kristina 
Published: December 2024

We examine how dimensions of information technology (IT) strategy affect the performance of young businesses, as well as dynamics as they age. Drawing from lifecycle theory and firm boundary research, we derive the relationship between age-based performance differences and IT sourcing decisions. We highlight the dynamic tension between outsourcing’s support for accessing frontier inputs in the short term and ownership’s advantages for developing organization-specific resources and capabilities over time. Leveraging a large panel of Census Bureau microdata from 2006 to 2014, we provide the first systematic evidence that young manufacturing establishments (both startups and new units of existing firms) disproportionately benefit from modern IT outsourcing (ITO). The young also enjoy productivity benefits from owned IT capital (ITK), despite high uncertainty, smaller operational scale, and less complementary organizational capital. Although these returns appear commensurate with those of older producers, they are conditional on survival, which is improved by ITO but harmed by ITK accumulation. Combining flexibility-related gains from ITK with vintage-related advantages in early ITK investment, the young are revealed to have significantly greater IT productivity than older incumbents. A large battery of tests supports a causal interpretation, as well as mechanisms rooted in mitigating the effects of uncertainty (as opposed to size- or cost-related reasons). These findings illuminate an often-overlooked pattern of young-business dynamism relevant to economic trends and management practices in an increasingly digital age. This paper was accepted by DJ Wu, information systems. Funding: This work was supported by the Social Sciences and Humanities Research Council (SSHRC) of Canada, the National Bureau of Economic Research, and the Stanford Digital Economy Lab. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2019.03116 .
An Stochastic Differential Equation Perspective on Stochastic Convex Optimization
Authors: Rodrigo Maulén S. , Fadili Jalal , Attouch Hedy 
Published: December 2024

In this paper, we analyze the global and local behavior of gradient-like flows under stochastic errors toward the aim of solving convex optimization problems with noisy gradient input. We first study the unconstrained differentiable convex case, using a stochastic differential equation where the drift term is minus the gradient of the objective function and the diffusion term is either bounded or square-integrable. In this context, under Lipschitz continuity of the gradient, our first main result shows almost sure convergence of the objective and the trajectory process toward a minimizer of the objective function. We also provide a comprehensive complexity analysis by establishing several new pointwise and ergodic convergence rates in expectation for the convex, strongly convex, and (local) Łojasiewicz case. The last involves a challenging local analysis which requires nontrivial arguments from measure theory. Then, we extend our study to the constrained case and more generally to nonsmooth problems. We show that several of our results have natural extensions obtained by replacing the gradient of the objective function by a cocoercive monotone operator. This makes it possible to obtain similar convergence results for optimization problems with an additively “smooth + nonsmooth” convex structure. Finally, we consider another extension of our results to nonsmooth optimization which is based on the Moreau envelope. Funding: This work was supported by Agence Nationale de la Recherche (ANR) [Grant ANR-20-CE92-0037-01].
Spray Drying of Fructooligosaccharide Syrup Produced from Jerusalem Artichoke Tuber Applying Different Drying Aids and Properties of Powder Products
Authors: Siriwarin Nattacha , Wichitchan Panisa , Thongchai Napassakorn , Jittanit Weerachet 
Published: December 2024

HighlightsFructooligosaccharide syrup was processed to powder form using spray-drying techniques.Various drying aids were applied in feed preparation to improve the spray-drying efficiency and powder characteristics.Powder recoveries obtained were higher than 50% and thus high enough for commercial production.Powder produced can be applied as functional ingredients in food and animal feed.Abstract. Fructooligosaccharide (FOS) syrup was produced using Jerusalem artichoke tuber (JAT) as the raw material. The syrup was processed to powder form by applying a spray-drying technique with inlet/outlet air temperatures of 190/90°C with three different drying aids comprising maltodextrin (MD), whey protein concentrate (WPC), and sodium caseinate (SCN) at various ratios. The key objectives of this study were to determine the suitable drying conditions by considering the powder recovery as well as to investigate the qualities of the different powders. The application of MD at the ratio of drying aid-to-total soluble solid in syrup of 1:1 w/w resulted in the highest values for powder recovery, bulk density, and water solubility and the lowest moisture content and hygroscopicity compared to its counterparts. Although the powder recovery using these conditions was 72.28%, the FOS content (the most desirable component in the powder product) was 33.53% d.b., which was clearly lower than that from using SCN at the ratio of 0.25:1 w/w that produced an FOS content of 50.26% d.b. However, the powder recovery using these conditions was 58.87%. These powder products could be applied as functional ingredients in food and animal feed, with their production costs being lower than those for the commercial high-purity FOS powder that requires more complicated processing techniques. Keywords: Fructooligosaccharide, Maltodextrin, Sodium caseinate, Spray-drying, Whey protein concentrate.