bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study
Authors: Ceolin C. , Scala A. , Dall’Agnol M. , Ziliotto C. , Delbarba A. , Facondo P. , Citron A. , Vescovi B. , Pasqualini S. , Giannini S. , Camozzi V. , Cappelli C. , Bertocco A. , De Rui M. , Coin A. , Sergi G. , Ferlin A. , Garolla A. ,   the Gender Incongruence Interdisciplinary Group (GIIG), Garolla Andrea , Aprile Anna , Azzena Bruno , Barbisan Camillo , Camozzi Valentina , Campello Elena , Annamaria Cattelan , Ceolin Chiara , Moro Fabrizio , Conti Giorgio , Favaro Angela , Ferlin Alberto , Francini Francesco , Gatta Michela , Ghisi Marta , Giannini Sandro , Guazzarotti Laura , Iafrate Massimo , Meneguzzo Paolo , Miscioscia Marina , Ottaviano Giancarlo , Saccardi Carlo , Sasset Lolita , Scala Alberto , Schiavo Rossana , Sergi Giuseppe , Simioni Paolo , Tascini Benedetta , Venturini Francesca , Vianello Fabrizio 
Published: July 2023

Abstract
Purpose
Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity).

Methods
Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ).

Results
14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people.

Conclusions
Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.
Estimating the change in the rational runoff coefficient through history in Jefferson County, Texas
Authors: Muppavarapu Nayana , Haselbach Liv 
Published: July 2023

AbstractJefferson County in Texas has experienced devastating storms in recent years resulting in billions of dollars in damages. The county has gone through temporal milestones in terms of population growth and industrial development. Many studies have shown that urban development increases the risk of flooding by decreasing the soil infiltration capacity. The current study focuses on estimating the extent to which the urban development in the county has led to increased imperviousness using a combination of historical and current spatial data. Rational runoff coefficients of the County were estimated and compared at three different times over a span of 120 years. A land survey map for 1898, an aerial imagery map for 1966 and a land parcel map for 2019 were obtained from various sources. The three maps available, each in different format, were analyzed to determine the land use and land cover type for the respective years. The runoff coefficient increased by 21% from 1898 to 1966 and remained the same from 1966 till 2019. The estimates are in correlation with industrial and population growth patterns of the county. These preliminary spatial analyses are useful in estimating the contributions of recent major flooding from overall development, or if they may be more impacted from other factors such as changes in weather patterns.
Potential for NPY receptor–related therapies for polycystic ovary syndrome: an updated review
Authors: Chen Wei-hong , Shi Yan-chuan , Huang Qiao-yi , Chen Jia-ming , Wang Zhi-yi , Lin Shu , Shi Qi-yang 
Published: July 2023

AbstractPolycystic ovary syndrome (PCOS) is a complex endocrine disease that can cause female infertility and bring economic burden to families and to society. The clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, and polycystic ovarian changes, often accompanied by insulin resistance and obesity. Although its pathogenesis is unclear, PCOS involves the abnormal regulation of the hypothalamic-pituitary-ovarian axis and the abnormal activation of GnRH neurons. Neuropeptide Y (NPY) is widely distributed in the arcuate nucleus of the hypothalamus and functions as the physiological integrator of two neuroendocrine systems, one governing feeding and the other controlling reproduction. In recent years, an increasing number of studies have focused on the improvement of the reproductive and metabolic status of PCOS through the therapeutic application of NPY and its receptors. In this review, we summarize the central and peripheral regulation of NPY and its receptors in the development of PCOS and discuss the potential for NPY receptor–related therapies for PCOS.
Artificial intelligence and algorithmic decisions in fraud detection: An interpretive structural model
Authors: Tan Evrim , Petit Jean Maxime , Simonofski Anthony , Tombal Thomas , Kleizen Bjorn , Sabbe Mathias , Bechoux Lucas , Willem Pauline 
Published: July 2023

Abstract
The use of artificial intelligence and algorithmic decision-making in public policy processes is influenced by a range of diverse drivers. This article provides a comprehensive view of 13 drivers and their interrelationships, identified through empirical findings from the taxation and social security domains in Belgium. These drivers are organized into five hierarchical layers that policy designers need to focus on when introducing advanced analytics in fraud detection: (a) trust layer, (b) interoperability layer, (c) perceived benefits layer, (d) data governance layer, and (e) digital governance layer. The layered approach enables a holistic view of assessing adoption challenges concerning new digital technologies. The research uses thematic analysis and interpretive structural modeling.
Treated, hospital-onset Clostridiodes difficile infection: An evaluation of predictors and feasibility of benchmarking comparing 2 risk-adjusted models among 265 hospitals
Authors: Yu Kalvin C. , Ye Gang , Edwards Jonathan R. , Dantes Raymund , Gupta Vikas , Ai ChinEn , Betz Kristina , Benin Andrea L. 
Published: July 2023

AbstractObjectives:To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data.Methods:We analyzed 9,134,276 admissions from 265 hospitals during 2015–2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates.Results:The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023–0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model.Conclusions:Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.
Didymus Chalcenterus and Aristophanes’ twoPlutusplays
Authors: Willi Andreas 
Published: July 2023

AbstractA variety of ancient sources suggest that there was more than one Aristophanic play entitled Πλοῦτος, and the scholia on the extantPlutusshow that one ancient commentator erroneously thought that he was working on a comedy of 408 BC when in reality he had the comedy of 388 BC in front of him. This error, which most likely arose because there were two similar versions of the latePlutus, has often been attributed to the first-century BC scholar Didymus Chalcenterus. It is here argued that the basis for this ascription is weak and that there are in fact substantial counter-arguments. Instead of Didymus, a later commentator such as the second-century AD scholar Symmachus may have been responsible for the mistake, which probably had more to do with the evolving transmission history of Aristophanes’ comedies than with careless scholarship.
Impact of musical training in specialised centres on learning strategies, auditory discrimination and working memory in adolescents
Authors: Sepúlveda-Durán Carmen María , Martín-Lobo Pilar , Santiago-Ramajo Sandra 
Published: July 2023

AbstractThe aim of this study was to analyse whether specialised musical training influences auditory discrimination, working memory, learning strategies and academic performance. Sixty students (30 with at least four years of musical training and 30 without) of the same socioeconomic level were compared. Significant differences were found between students with and without musical training in terms of learning strategies, working memory and academic performance (p= <.05). This study shows the benefits of musical training offered at specialised centres, the development of students’ cognitive skills and the contributions of neuroscience to improving professional practice.
CHAD for expressive total languages
Authors: Lucatelli Nunes Fernando , Vákár Matthijs 
Published: July 2023

AbstractWe show how to apply forward and reverse mode Combinatory Homomorphic Automatic Differentiation (CHAD) (Vákár (2021). ESOP, 607–634; Vákár and Smeding (2022). ACM Transactions on Programming Languages and Systems44 (3) 20:1–20:49.) to total functional programming languages with expressive type systems featuring the combination of
•tuple types;•sum types;•inductive types;•coinductive types;•function types.We achieve this by analyzing the categorical semantics of such types in
$\Sigma$
-types (Grothendieck constructions) of suitable categories. Using a novel categorical logical relations technique for such expressive type systems, we give a correctness proof of CHAD in this setting by showing that it computes the usual mathematical derivative of the function that the original program implements. The result is a principled, purely functional and provably correct method for performing forward- and reverse-mode automatic differentiation (AD) on total functional programming languages with expressive type systems.
BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis
Authors: Huang Chongbiao , Li Hui , Xu Yang , Xu Chao , Sun Huizhi , Li Zengxun , Ge Yi , Wang Hongwei , Zhao Tiansuo , Gao Song , Wang Xiuchao , Yang Shengyu , Sun Peiqing , Liu Zhe , Liu Jing , Chang Antao , Hao Jihui 
Published: July 2023

AbstractVEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors. Nevertheless, pancreatic adenocarcinoma (PAAD) cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways, thereby conferring resistance to VEGF inhibitors. Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD. The analysis of our own cohort confirmed that BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth, and worse prognosis. In cells and mice with xenograft tumors, BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent manner. Mechanistically, as an RNA binding protein, BICC1 bounds to the 3’UTR of Lipocalin-2 (LCN2) mRNA and post-transcriptionally up-regulated LCN2 expression in PAAD cells. When its level is elevated, LCN2 binds to its receptor 24p3R, which directly phosphorylates JAK2 and activates JAK2/STAT3 signal, leading to increased production of an angiogenic factor CXCL1. Blocking of the BICC1/LCN2 signalling reduced the microvessel density and tumor volume of PAAD cell grafts in mice, and increased the tumor suppressive effect of gemcitabine. In conclusion, BICC1 plays a pivotal role in the process of VEGF-independent angiogenesis in pancreatic cancer, leading to resistance to VEGF inhibitors. BICC1/LCN2 signaling may serve as a promising anti-angiogenic therapeutic target for pancreatic cancer patients.
The inhibition of FKBP5 protects β-cell survival under inflammation stress via AKT/FOXO1 signaling
Authors: Liu Na , Li Rui , Cao Jinglin , Song Xinyao , Ma Wenmiao , Liu Tengli , Wang Le , Zou Jiaqi , Zhang Boya , Liu Zewen , Liang Rui , Zheng Rongxiu , Wang Shusen 
Published: July 2023

AbstractThe FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in β cells, which secrete the only glucose-lowering hormone—insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in β cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted β-cell survival, improved insulin secretion, and upregulated β-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed β cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in β cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in β cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.
Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner
Authors: Fu Xiuling , Zhuang Qiang , Babarinde Isaac A. , Shi Liyang , Ma Gang , Hu Haoqing , Li Yuhao , Chen Jiao , Xiao Zhen , Deng Boping , Sun Li , Jauch Ralf , Hutchins Andrew P. 
Published: July 2023

AbstractSomatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using oncogenic transgenes and discovered transformed cell lines compatible with reprogramming when transfected with Oct4/Sox2/Klf4/Myc. By comparing the reprogramming-capable and incapable transformed lines we identified multiple stages of failure in the reprogramming process. Some transformed lines failed at an early stage, whilst other lines seemed to progress through a conventional reprogramming process. Finally, we show that MEK inhibition overcomes one critical reprogramming barrier by indirectly suppressing a hyperacetylated active epigenetic state. This study reveals that diverse epigenetic barriers underly resistance to reprogramming of transformed cells.
Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A
Authors: Chen Chih-Wei , Leimer Nadja , Syroegin Egor A. , Dunand Clémence , Bulman Zackery P. , Lewis Kim , Polikanov Yury S. , Svetlov Maxim S. 
Published: July 2023

AbstractThe ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent a potential approach to more efficiently combat infections caused by susceptible and drug-resistant bacteria, only a few known drug pairs exhibit synergy/cooperativity in killing bacteria. Here, we discover that well-known ribosomal antibiotics, hygromycin A (HygA) and macrolides, which target peptidyl transferase center and peptide exit tunnel, respectively, can act cooperatively against susceptible and drug-resistant bacteria. Remarkably, HygA slows down macrolide dissociation from the ribosome by 60-fold and enhances the otherwise weak antimicrobial activity of the newest-generation macrolide drugs known as ketolides against macrolide-resistant bacteria. By determining a set of high-resolution X-ray crystal structures of drug-sensitive wild-type and macrolide-resistant Erm-methylated 70S ribosomes in complex with three HygA-macrolide pairs, we provide a structural rationale for the binding cooperativity of these drugs and also uncover the molecular mechanism of overcoming Erm-type resistance by macrolides acting together with hygromycin A. Altogether our structural, biochemical, and microbiological findings lay the foundation for the subsequent development of synergistic antibiotic tandems with improved bactericidal properties against drug-resistant pathogens, including those expressing erm genes.
Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement
Authors: Ghosh Sourav , Kundu Rajib , Chandana Manjunatha , Das Rahul , Anand Aditya , Beura Subhashree , Bobde Ruchir Chandrakant , Jain Vishal , Prabhu Sowmya Ramakant , Behera Prativa Kumari , Mohanty Akshaya Kumar , Chakrapani Mahabala , Satyamoorthy Kapaettu , Suryawanshi Amol Ratnakar , Dixit Anshuman , Padmanaban Govindarajan , Nagaraj Viswanathan Arun 
Published: July 2023

AbstractMalaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids. Interestingly, a putative gene for glutamine synthetase (GS) is retained despite glutamine being an abundant amino acid in human and mosquito hosts. Here we show Plasmodium GS has evolved as a unique type I enzyme with distinct structural and regulatory properties to adapt to the asexual niche. Methionine sulfoximine (MSO) and phosphinothricin (PPT) inhibit parasite GS activity. GS is localized to the parasite cytosol and abundantly expressed in all the life cycle stages. Parasite GS displays species-specific requirement in Plasmodium falciparum (Pf) having asparagine-rich proteome. Targeting PfGS affects asparagine levels and inhibits protein synthesis through eIF2α phosphorylation leading to parasite death. Exposure of artemisinin-resistant Pf parasites to MSO and PPT inhibits the emergence of viable parasites upon artemisinin treatment.
Trait anxiety is associated with hidden state inference during aversive reversal learning
Authors: Zika Ondrej , Wiech Katja , Reinecke Andrea , Browning Michael , Schuck Nicolas W. 
Published: July 2023

AbstractUpdating beliefs in changing environments can be driven by gradually adapting expectations or by relying on inferred hidden states (i.e. contexts), and changes therein. Previous work suggests that increased reliance on context could underly fear relapse phenomena that hinder clinical treatment of anxiety disorders. We test whether trait anxiety variations in a healthy population influence how much individuals rely on hidden-state inference. In a Pavlovian learning task, participants observed cues that predicted an upcoming electrical shock with repeatedly changing probability, and were asked to provide expectancy ratings on every trial. We show that trait anxiety is associated with steeper expectation switches after contingency reversals and reduced oddball learning. Furthermore, trait anxiety is related to better fit of a state inference, compared to a gradual learning, model when contingency changes are large. Our findings support previous work suggesting hidden-state inference as a mechanism behind anxiety-related to fear relapse phenomena.
HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search
Authors: Lee Yi-Yuan , Guler Mustafa , Chigumba Desnor N. , Wang Shen , Mittal Neel , Miller Cameron , Krummenacher Benjamin , Liu Haodong , Cao Liu , Kannan Aditya , Narayan Keshav , Slocum Samuel T. , Roth Bryan L. , Gurevich Alexey , Behsaz Bahar , Kersten Roland D. , Mohimani Hosein 
Published: July 2023

AbstractRecent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.