bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the environmental impact of endoscopic activity at a tertiary center: a pilot study
Authors: Ribeiro Tiago , Morais Rui , Monteiro Cristiana , Carvalho Ana , Barros Sónia , Fernando André , Pioche Mathieu , de Santiago Enrique Rodríguez , Macedo Guilherme 
Published: November 2023

Introduction
The growing number of endoscopic procedures, frequently requiring single-use disposable instruments, is responsible for the production of a large amount of waste. To this date, the reality of waste production at large European Gastroenterology centers is unknown. This study aimed to estimate the amount of waste due to endoscopic practice at a tertiary center in Portugal.

Methods
We performed a prospective study to calculate the mass (in kg) of residues generated during a period of 5 working days of endoscopic practice. We included residues produced at endoscopy suites, pre and postprocedure areas and during endoscope reprocessing. Residues were categorized as non-dangerous (groups I/II), of biologic risk (group III) and specific hazardous hospital residues (group IV). The production of residues separated for recycling/valorization (paper/card and plastic) was also quantified. The volume of water used for reprocessing an endoscope was also assessed.

Results
During the analyzed period, 241 endoscopic procedures were performed. A total of 443.2 kg of waste (22.6 kg from groups I/II, 266.9 kg from group III and 3.9 kg from group IV) were produced, most from group III (75%). For each endoscopic procedure, 1.8 kg of waste was generated. Of the total waste mass, 17.8% was separated for recycling/valorization. A volume of 55L of water was required for reprocessing one endoscope.

Conclusion
Each endoscopic procedure generated a significant amount of waste and water consumption during reprocessing. These real-life analyses are a pivotal step before implementing effective measures to improve resource utilization and more sustainable practices.
Factors Influencing Intention on Condom Use During Sexual Intercourse With Regular Female Partners Among Men Who Have Sex With Men in Western China: A Structural Equation Modeling Analysis
Authors: Cao Zhen , Chen Jin , Lin Bing , Zhang Cong , Zhong Xiaoni 
Published: November 2023

Background
Given the rapid rise in HIV infection among men who have sex with men (MSM) in China, they may be a potential bridge for HIV transmission to the general female population, and increasing condom use is an important protective measure. This study aimed to explore factors that influence the intention of condom use during sexual intercourse with regular female partners among MSM in Western China, based on the Health Action Process Approach model.

Methods
This study used a baseline sample from a cohort study of the National Science and Technology Major Project. A nonprobability sampling method was adopted to recruit MSM from western China. Information on sociodemographic characteristics, HIV-related characteristics, sexual behavior, and constructs of the Health Action Process Approach model was collected through structured questionnaires, and the data were analyzed using a structural equation model.

Results
Among 232 participants, 62.9% (146 of 232) intended to use condoms every time they had sex with their regular female partners during the following 3 months. The results of the structural equation model showed that self-efficacy had the greatest influence on behavioral intention (β = 0.398, P < 0.001), followed by negative outcome expectancy (β = −0.303, P < 0.05). In addition, risk perception (β = 0.206, P < 0.05) and positive outcome expectancy (β = 0.270, P < 0.01) had indirect effects on intention, whereas self-efficacy played a mediating role in these indirect influencing factors.

Conclusions
Risk perception, outcome expectancy, and self-efficacy are predictors of condom use intention, with self-efficacy in particular serving as a significant medium for future interventions. These findings could provide a reference for future targeted interventions to reduce the likelihood of HIV transmission from MSM to the female population.
Modified Furlow Palatoplasty Using Small Double-Opposing Z-Plasty: Long-Term Outcome and Comparison with 2-Flap Palatoplasty
Authors: Hattori Yoshitsugu , Pai Betty Chien-Jung , Saito Takafumi , Tu Junior Chun-Yu , Chou Pang-Yun , Lo Lun-Jou 
Published: November 2023

Background:
Postpalatoplasty velopharyngeal function needs to be evaluated through long-term follow-up, but such reports are limited in the literature, and there has been no consensus as to which surgical technique yields optimal velopharyngeal function with minimum complication rate. This study aimed to evaluate the long-term outcome of the modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ).

Methods:
A retrospective review was conducted of consecutive patients who underwent palatoplasty performed by the senior author (L.J.L.) between January of 2000 and March of 2014. Nonsyndromic patients who underwent palatoplasty before the age of 18 months and followed up until at least 9 years of age were included. Comparisons between the small-DOZ and 2-flap methods for soft palate repair were made.

Results:
A total of 196 small-DOZ and 167 2-flap palatoplasty patients were eligible in the study. Among the small-DOZ palatoplasty patients, 1 patient (0.5%) developed oronasal fistula and 18 patients (9.2%) developed velopharyngeal insufficiency (VPI) surgery (10 patients at preschool age, and 8 at 9 years of age). Compared with the small-DOZ palatoplasty, the oronasal fistula rate, VPI surgery rate, and the need for myringotomy tube insertion were significantly higher in the 2-flap group (P = 0.01, P < 0.01, and P < 0.01, respectively). Patients who developed oronasal fistula had significantly higher likelihood of having VPI (P < 0.01).

Conclusions:
The small-DOZ provided successful palatal repair with low rates of oronasal fistula and VPI in the long term. Wound closure under minimal tension facilitated avoiding oronasal fistula. Reconstruction of the functional muscle sling enabled the authors to achieve normal velopharyngeal function with favorable speech outcome and middle ear function.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Topical siRNA therapy of diabetic-like wound healing
Authors: Neuhoferova Eva , Kindermann Marek , Buzgo Matej , Vocetkova Karolina , Panek Dalibor , Cigler Petr , Benson Veronika 
Published: November 2023

ABSTRACTNon-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing and is therefore of great interest. Here we focused on development of gene silencing system for localized delivery of antisense siRNA against MMP-9 into the wound. We have developed a functional and biocompatible wound dressing allowing controlled release of a traceable vector loaded with the target siRNA. Specifically, the dressing consists of a degradable scaffold of polymer nanofibers embedded with the vector nanosystem, polymer-coated fluorescent nanodiamonds (FNDs). The biocompatible cationic polymer shell on FNDs was designed and optimized for binding of siRNA and formation of colloidally stable FND-siRNA complexes in physiological environment. A hybrid nanofiber scaffold consisting of poly(vinyl alcohol) and poly(caprolactone) ensured continuous release of FND-siRNA complexes from the dressing. The photostable luminescence of FNDs allowed us to monitor the vector system in the wound. Our dressing was tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms ofin vivotoxicity, biological efficacy and manipulation. The treatment resulted in significant local inhibition of MMP-9 and reduction of the wound healing time. The scar formation for treated diabetic-like animals became comparable with non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach in gene therapy of non-healing wounds.
Daily time constraints limit behavioural capacity to cope with thermally increased metabolic demands
Authors: Byrnes Evan E. , Adam Timo , Feldmann Carlina C. , Kaplinskaya Larisa , Sticker Kevin , Fredebeul Raphael Joshua , Lear Karissa O. , Morgan David L. , Beatty Stephen J. , Langrock Roland , Gleiss Adrian C. 
Published: November 2023

AbstractIncreased environmental temperatures result in greater energy demands for ectotherms, however, it is currently not clear if these energy demands can effectively be met by increased foraging effort. Here, we tested the temperature dependence of foraging effort and metabolic rate in an aquatic ectotherm across its entire natural thermal range. We developed a novel hidden Markov model to detect behavioural states in long-term body acceleration data collected from free-ranging bull sharks between 19 and 33 °C, and found that increasing temperature altered both the timing and extent of foraging effort. Our data revealed asymmetrical increases of metabolic demands and foraging effort; standard metabolic rates increased exponentially with temperature, but foraging effort increased logarithmically. The observed decoupling of foraging effort and energy demand suggests individuals face increased energy deficits at higher temperatures, confirmed by concomitant reductions in body condition measured in this population with increasing temperatures. We suggest that alterations in the well-established trade-offs between foraging and predation risk coupled with time constraints imposed by high temperatures limit the capacity of animals to cope with environmental temperatures well below critical temperatures.
Determination of Metabolic Fluxes by Deep Learning of Isotope Labeling Patterns
Authors: Law Richard C. , O’Keeffe Samantha , Nurwono Glenn , Ki Rachel , Lakhani Aliya , Lai Pin-Kuang , Park Junyoung O. 
Published: November 2023

AbstractFluxomics offers a direct readout of metabolic state but relies on indirect measurement. Stable isotope tracers imprint flux-dependent isotope labeling patterns on metabolites we measure; however, the relationship between labeling patterns and fluxes remains elusive. Here we innovate a two-stage machine learning framework termed ML-Flux that streamlines metabolic flux quantitation from isotope tracing. We train machine learning models by simulating atom transitions across five universal metabolic models starting from 2613C-glucose,2H-glucose, and13C-glutamine tracers within feasible flux space. ML-Flux employs deep-learning-based imputation to take variable measurements of labeling patterns as input and successive neural networks to convert the ensuing comprehensive labeling information into metabolic fluxes. Using ML-Flux with multi-isotope tracing, we obtain fluxes through central carbon metabolism that are comparable to those from a least-squares method but orders-of-magnitude faster. ML-Flux is deployed as a webtool to expand the accessibility of metabolic flux quantitation and afford actionable information on metabolism.
Sex chromosome turnover in hybridizing stickleback lineages
Authors: Yi Xueling , Wang Dandan , Reid Kerry , Feng Xueyun , Löytynoja Ari , Merilä Juha 
Published: November 2023

AbstractRecent discoveries of sex chromosome diversity across the tree of life have challenged the canonical model of conserved sex chromosome evolution and evoked new theories on labile sex chromosomes that maintain less differentiation and undergo frequent turnover. However, theories of labile sex chromosome evolution lack direct empirical support due to the paucity of case studies demonstrating ongoing sex chromosome turnover in nature. Two divergent lineages (viz. WL & EL) of nine-spined sticklebacks (Pungitius pungitius) with different sex chromosomes (linkage group [LG] 12 in the EL, unknown in the WL) hybridize in a natural secondary contact zone in the Baltic Sea, providing an opportunity to study ongoing turnover between coexisting sex chromosomes. We first identified an 80 kbp genomic region on LG3 as the sex-determining region (SDR) using whole-genome resequencing data of family crosses. We then verified this region as the SDR in most other WL populations and demonstrated an ongoing sex chromosome turnover in admixed marine populations where the evolutionarily younger and homomorphic LG3 sex chromosomes replace the older and heteromorphic LG12 sex chromosomes. The results provide a rare glimpse of ongoing sex chromosome turnover and indicate possible existence of additional but yet undiscovered sex chromosome diversity inPungitiussticklebacks.TeaserEvolutionarily young sex chromosomes replace the older ones in the hybrid zone of EuropeanPungitiusstickleback lineages.
Network medicine-based epistasis detection in complex diseases: ready for quantum computing
Authors: Hoffmann Markus , Poschenrieder Julian M. , Incudini Massimiliano , Baier Sylvie , Fitz Amelie , Maier Andreas , Hartung Michael , Hoffmann Christian , Trummer Nico , Adamowicz Klaudia , Picciani Mario , Scheibling Evelyn , Harl Maximilian V. , Lesch Ingmar , Frey Hunor , Kayser Simon , Wissenberg Paul , Schwartz Leon , Hafner Leon , Acharya Aakriti , Hackl Lena , Grabert Gordon , Lee Sung-Gwon , Cho Gyuhyeok , Cloward Matthew , Jankowski Jakub , Lee Hye Kyung , Tsoy Olga , Wenke Nina , Pedersen Anders Gorm , Bønnelykke Klaus , Mandarino Antonio , Melograna Federico , Schulz Laura , Climente-Gonzalez Héctor , Wilhelm Mathias , Iapichino Luigi , Wienbrandt Lars , Ellinghaus David , Van Steen Kristel , Grossi Michele , Furth Priscilla A. , Hennighausen Lothar , Di Pierro Alessandra , Baumbach Jan , Kacprowski Tim , List Markus , Blumenthal David B. 
Published: November 2023

AbstractMost heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs)1–3. Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-basedepistasisdetection vialocal search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL is the first application that demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies.
MS/MS fragmentation pattern analysis confirms the production of the new esterified bile acids by the human gut microbiota
Authors: Garcia Carlos J. , García-Villalba Rocio , Beltrán David , Frutos-Lisón Maria D. , Tomás-Barberán Francisco A. 
Published: November 2023

AbstractThe pathophysiology of bile acids (BAs) has been widely studied. The BAs are signaling molecules that affect lipids and glucose homeostasis via activation of BAs FRX and TGR5 receptors in the liver and peripheral tissues. The ratio of conjugated/unconjugated BAs seems relevant to quantify these interactions and, therefore, the impact on the metabolism. The gut microbiota plays a key role because they convert the primary BAs into the secondary BAs, hydrolyzes the hepatically conjugated BAs and re-conjugates BAs with amino acids. New re-conjugated BAs with amino acids (MCBAs) in the form of amides or esters have been recently suggested, but it was not possible to confirm them. This study evaluates the production of MCBAs by human gut microbiota in in vitro colonic fermentations and designs a bioanalytical method to discriminate between amides and esters. Amides and seven new esters of re-conjugated BAs composed of lithocholic acid conjugated with leucine, valine and aminobutyric acid were identified and confirmed by MS/MS after incubation with chenodeoxycholic acid and lithocholic acid. There were no specific fragments in negative polarity to discriminate between amides and esters. However, in positive polarity the amides showed a characteristic MS/MS fragment consisting of the loss of water from the released amino acid, while the esters showed the loss of water plus carbon monoxide. This study confirmed for the first time the presence of esterified MCBAs, in addition to amides, and characterized the specific MS/MS fragmentation patterns to identify and discriminate them. These results show for the first time the existence of re-conjugated BAs by ester bond and the capability to produce them by the gut microbes. This bioanalytical method will allow including these new MCBAs in the BAs analysis.
Novel role ofPeriploca laevigataextracts as anti-diabetic and anti-inflammatory function in pancreatic β cells exposed to hyperglycaemia
Authors: Trabelsi Ghada , Mellado Susana , Kalboussi Zahar , Chekir-Ghedira Leila , Pascual María 
Published: November 2023

ABSTRACTType 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is associated with high blood glucose levels due to insufficient insulin production by the pancreas, leading to an inflammatory immune response. Considering the beneficial roles of medicinal plants to control the diabetic complications of T2D, as well as the therapeutic roles of the extracts fromPeriploca laevigata(PL), this study evaluates the anti-diabetic and anti-inflammatory properties of PL extracts in the pancreatic β cell line INS-1E under hyperglycaemic. Our findings demonstrated, for the first time, that whereas PL extracts tends to upregulate the insulin gene expression, PL extract from leaves increase significantly the gene expression of GLUT-2 and the transcription factor PDX-1 in glucose-treated INS-1E cells. Notably, some PL extracts are also capable to decrease significantly the gene expression of iNOS and to increase the IL-10 gene expression in glucose-treated INS-1E cells. However, the PL extracts show a tendency to decrease the gene expression of NF-kB and MCP-1 in glucose-treated INS-1E cells. In conclusion, our findings suggest that the treatment with PL extracts could benefit the pancreatic β cell function and alleviate the pancreatic inflammation, thereby representing potential advantages of the glucose metabolism in the T2D.
Signals of microbial growth learned from single amplicon samples
Authors: Chlenski Philippe , Ricaurte Deirdre , Pe’er Itsik 
Published: November 2023

AbstractIrregularities in metagenomic whole-genome shotgun (WGS) read coverage can arise in quickly replicating microbial populations. These irregularities, summarized as peak-to-trough ratios (PTRs), are correlated with growth rates. This study seeks to explore the presence of similar coverage irregularities in 16S amplicon datasets, where multicopy diverged 16S genes provide an opportunity to explore coverage at different positions on the bacterial chromosome. To this end, we propose a model of Operational Taxonomic Unit (OTU) observations under replication and sequence similarity, from which we derive a method for simultaneous copy number correction and dynamics estimation by gradient descent. We conduct a series of benchmarks on synthetic data, determining a set of heuristics for when such methods may be applied, and compare our method with WGS-based methods on a real dataset. We find no correlation between coPTR estimates and our method, suggesting further modifications to our method may be required.
MYC amplifies mitotic perturbations elicited by LXY18 to enable synthetic lethality
Authors: Kalashova Julia , Yang Chenglu , Long Yan , Li Hongmei , Zhang Shenqiu , Zhang Ting , Yu Duo , Liu Xumei , Lv Gang , Choudhry Namrta , Liu Hong , Shi Qiong , Yang Dun 
Published: November 2023

AbstractThe MYC oncoprotein represents an intriguing target for cancer treatment, but its therapeutic potential has been hindered by the absence of specific pharmacological inhibitors. In this study, we demonstrate that the phenoxy quinoline compound LXY18 selectively targets and eliminates cells overexpressing MYC, leaving non-transformed cells unharmed. This synthetic lethality arises from an acute induction of multipolarity, resulting in a persistent arrest in early mitosis followed by cell death in mitosis or after mitotic slippage. Distinctively, LXY18’s action contrasts with other antimitotic compounds, as they either fail to induce mitotic arrest or elicit mitotic arrest irrespective of MYC abundance. Furthermore, the MYC abundance in a panel of 98 tumor cell lines correlates with their sensitivity to LXY18. Collectively, our findings uncover LXY18 as an MYC- enabled mitotic blocker and open a new avenue to selectively target MYC-overexpressing tumor cells without affecting normal cells.
Feeding-structure morphogenesis in “rhabditid” and diplogastrid nematodes is not controlled by a conserved genetic module
Authors: Theska Tobias , Sommer Ralf J. 
Published: November 2023

AbstractDisentangling the evolution of the molecular processes and genetic networks that facilitate the emergence of morphological novelties is one of the main objectives in evolutionary developmental biology. Here, we investigated the evolutionary history of a gene regulatory network controlling the development of novel tooth-like feeding-structures in diplogastrid nematodes. Focusing on NHR-1 and NHR-40, the two transcription factors that regulate the morphogenesis of these feeding structures inPristionchus pacificus, we sought to determine whether they have a similar function in out-group nematodeCaenorhabditis elegans, which has typical “rhabditid” flaps instead of teeth. Contrary to our initial expectations, we found that they do not have a similar function. While both receptors are co-expressed in the tissues that produce the feeding structures in the two nematodes, genetic inactivation of either receptor had no impact on feeding-structure morphogenesis inC. elegans. Transcriptomic experiments revealed that NHR-1 and NHR-40 have highly species-specific regulatory targets. These results suggest two possible evolutionary scenarios: either the genetic module responsible for feeding-structure morphogenesis in Diplogastridae already existed in the last common ancestor ofC. elegansandP. pacificus, and subsequently disintegrated in the former as NHR-1 and NHR-40 acquired new targets, or it evolved in conjunction with teeth in Diplogastridae. These findings indicate that feeding-structure morphogenesis is regulated by different genetic programs inP. pacificusandC. elegans, hinting at developmental systems drift during the flap-to-tooth transformation. Further research in other “rhabditid” species is needed to fully reconstruct the developmental genetic changes which facilitated the evolution of novel feeding structures in Diplogastridae.Research HighlightsCombining CRISPR-based mutagenesis, geometric morphometrics, and transcriptomics, we found that the genetic module governing the morphogenesis of novel feeding structures in diplogastrid nematodes is not conserved in the “rhabditid”C. elegans.