bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple stressor effects of insecticide exposure and increased fine sediment deposition on the gene expression profiles of two freshwater invertebrate species
Authors: Brasseur Marie V. , Buchner Dominik , Mack Leoni , Schreiner Verena C. , Schäfer Ralf B. , Leese Florian , Mayer Christoph 
Published: September 2023

Abstract
Background
Freshwater ecosystem degradation and biodiversity decline are strongly associated with intensive agricultural practices. Simultaneously occurring agricultural stressors can interact in complex ways, preventing an accurate prediction of their combined effects on aquatic biota. Here, we address the limited mechanistic understanding of multiple stressor effects of two globally important stressors, an insecticide (chlorantraniliprole), and increased fine sediment load and assessed their impact on the transcriptomic profile of two stream macroinvertebrates: the amphipod Gammarus pulex and the caddisfly Lepidostoma basale.

Results
We identified mainly antagonistic stressor interactions at the transcriptional level, presumably because the insecticide adsorbed to fine sediment particles. L. basale, which is phylogenetically more closely related to the insecticide’s target taxon Lepidoptera, exhibited strong transcriptional changes when the insecticide stressor was applied, whereas no clear response patterns were observed in the amphipod G. pulex. These differences in species vulnerability can presumably be attributed to molecular mechanisms determining the cellular affinity toward a stressor as well as differential exposure patterns resulting from varying ecological requirements between L. basale and G. pulex. Interestingly, the transcriptional response induced by insecticide exposure in L. basale was not associated with a disruption of the calcium homeostasis, which is the described mode of action for chlorantraniliprole. Instead, immune responses and alterations of the developmental program appear to play a more significant role.

Conclusions
Our study shows how transcriptomic data can be used to identify multiple stressor effects and to explore the molecular mechanisms underlying stressor-induced physiological responses. As such, stressor effects assessed at the molecular level can inform about modes of action of chemicals and their interplay with non-chemical stressors. We demonstrated that stressor effects vary between different organismic groups and that insecticide effects are not necessarily covered by their described mode of action, which has important implications for environmental risk assessment of insecticides in non-target organisms.
ECL 3.0: a sensitive peptide identification tool for cross-linking mass spectrometry data analysis
Authors: Zhou Chen , Dai Shuaijian , Lai Shengzhi , Lin Yuanqiao , Zhang Xuechen , Li Ning , Yu Weichuan 
Published: September 2023

Abstract
Background
Cross-linking mass spectrometry (XL-MS) is a powerful technique for detecting protein–protein interactions (PPIs) and modeling protein structures in a high-throughput manner. In XL-MS experiments, proteins are cross-linked by a chemical reagent (namely cross-linker), fragmented, and then fed into a tandem mass spectrum (MS/MS). Cross-linkers are either cleavable or non-cleavable, and each type requires distinct data analysis tools. However, both types of cross-linkers suffer from imbalanced fragmentation efficiency, resulting in a large number of unidentifiable spectra that hinder the discovery of PPIs and protein conformations. To address this challenge, researchers have sought to improve the sensitivity of XL-MS through invention of novel cross-linking reagents, optimization of sample preparation protocols, and development of data analysis algorithms. One promising approach to developing new data analysis methods is to apply a protein feedback mechanism in the analysis. It has significantly improved the sensitivity of analysis methods in the cleavable cross-linking data. The application of the protein feedback mechanism to the analysis of non-cleavable cross-linking data is expected to have an even greater impact because the majority of XL-MS experiments currently employs non-cleavable cross-linkers.

Results
In this study, we applied the protein feedback mechanism to the analysis of both non-cleavable and cleavable cross-linking data and observed a substantial improvement in cross-link spectrum matches (CSMs) compared to conventional methods. Furthermore, we developed a new software program, ECL 3.0, that integrates two algorithms and includes a user-friendly graphical interface to facilitate wider applications of this new program.

Conclusions
ECL 3.0 source code is available at https://github.com/yuweichuan/ECL-PF.git. A quick tutorial is available at https://youtu.be/PpZgbi8V2xI.
Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits
Authors: Cheng Youshu , Justice Amy , Wang Zuoheng , Li Boyang , Hancock Dana B. , Johnson Eric O. , Xu Ke 
Published: September 2023

AbstractBackgroundCocaine use (CU) is associated with psychiatric and medical diseases. Little is known about the mechanisms of CU-related comorbidities. Findings from preclinical and clinical studies have suggested that CU is associated with aberrant DNA methylation (DNAm) that may be influenced by genetic variants [i.e., methylation quantitative trait loci (meQTLs)]. In this study, we mapped cis-meQTLs for CU-associated DNAm sites (CpGs) in an HIV-positive cohort (Ntotal = 811) and extended the meQTLs to multiple traits.ResultsWe conducted cis-meQTL analysis for 224 candidate CpGs selected for their association with CU in blood. We identified 7,101 significant meQTLs [false discovery rate (FDR) < 0.05], which mostly mapped to genes involved in immunological functions and were enriched in immune pathways. We followed up the meQTLs using phenome-wide association study and trait enrichment analyses, which revealed 9 significant traits. We tested for causal effects of CU on these 9 traits using Mendelian Randomization and found evidence that CU plays a causal role in increasing hypertension (p-value = 2.35E-08) and decreasing heel bone mineral density (p-value = 1.92E-19).ConclusionsThese findings suggest that genetic variants for CU-associated DNAm have pleiotropic effects on other relevant traits and provide new insights into the causal relationships between cocaine use and these complex traits.
Drug-target binding affinity prediction using message passing neural network and self supervised learning
Authors: Xia Leiming , Xu Lei , Pan Shourun , Niu Dongjiang , Zhang Beiyi , Li Zhen 
Published: September 2023

Abstract
Background
Drug-target binding affinity (DTA) prediction is important for the rapid development of drug discovery. Compared to traditional methods, deep learning methods provide a new way for DTA prediction to achieve good performance without much knowledge of the biochemical background. However, there are still room for improvement in DTA prediction: (1) only focusing on the information of the atom leads to an incomplete representation of the molecular graph; (2) the self-supervised learning method could be introduced for protein representation.

Results
In this paper, a DTA prediction model using the deep learning method is proposed, which uses an undirected-CMPNN for molecular embedding and combines CPCProt and MLM models for protein embedding. An attention mechanism is introduced to discover the important part of the protein sequence. The proposed method is evaluated on the datasets Ki and Davis, and the model outperformed other deep learning methods.

Conclusions
The proposed model improves the performance of the DTA prediction, which provides a novel strategy for deep learning-based virtual screening methods.
In-vitro antibacterial activity and mechanism of Monarda didyma essential oils against Carbapenem-resistant Klebsiella pneumoniae
Authors: Chen Ying , Zhao Jinda , Liu Chenyu , Wu Dongmei , Wang Xianhe 
Published: September 2023

AbstractTo fight the global epidemic of drug-resistant bacteria, essential oils have gained increasing attention as a new source of antibiotics. The antimicrobial activity of Monarda didyma essential oils (MDEO) for the Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were determined by agar disc diffusion assay and broth microdilution assay. To further understand MDEO efficacy, a time-growth curve was performed. The biofilm formation of CRKP were determined by crystalline violet staining method, additionally, changes in intracellular Adenosine triphosphate (ATP), protein, Alkaline phosphatase (AKP) activities, and membrane integrity were investigated to assess the influence of MDEO on cell membrane damage. Finally, the activities of key enzymes in the tricarboxylic acid (TCA) pathways and pentose phosphate (PPP) pathways were examined to determine the effect of MDEO on the respiratory metabolism of CRKP. This study presents the antibacterial mechanism of MDEO against CRKP with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1.25 mg/ml. To understand MDEO efficacy, a time-kill kinetics approach was performed. The bactericidal effect of MDEO was evident at 2 h compared to the control at its MIC and 2MIC. Surface electron microscopic and ATP assay studies provided evidence for the multi-target action of MDEO against CRKP. MDEO could inhibit CRKP biofilm formation. MDEO could also cause irreversible damage to the CRKP cell membrane, resulting in the leakage of biological macromolecules (protein, ATP) and the reduction of intracellular enzymes (AKP) activities. Finally, MDEO affected the pathways of respiratory metabolism, such as PPP and TCA pathways. MDEO could reduce the activity of key enzymes (Glucose-6-phosphate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) in the PPP and TCA pathways to exert its biological effects against CRKP. These results suggest MDEO can exert inhibitory effects on CRKP, and potential mechanisms of action including inhibition of biofilm formation, damage of cell membrane structure and inhibition of energy metabolism.
Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology
Authors: Von Tokarski Florent , Fillon Alexandre , Maisons Valentin , Thoreau Benjamin , Bayer Guillaume , Gatault Philippe , Longuet Hélène , Sautenet Bénédicte , Buchler Matthias , Vigneau Cécile , Fakhouri Fadi , Halimi Jean-Michel 
Published: September 2023

Abstract
Background
Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant.
recipients (KTR).

Methods
We analysed the epidemiology of adjudicated TMA in consecutive KTR during the.
2009–2021 period.

Results
TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1–8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5–6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9–15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features.

Conclusions
TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.
Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study
Authors: Fang Tian , Zhang Zhihao , Zhou Huijie , Wu Wanchun , Ji Fuqing , Zou Liqun 
Published: September 2023

Abstract
Background
The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis.

Methods
We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements.

Results
Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035–1.110, P = 8.78 × 10− 5, false discovery rate (FDR) = 7.36 × 10− 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023–1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019–1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis.

Conclusion
This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.
Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms
Authors: Wang Hui , Liu Shu , Xie Liqing , Wang Jinhui 
Published: September 2023

Abstract
Background
Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it’s essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.

Methods
In this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.

Results
The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.

Conclusions
Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.
The role of the cultural environment in the development of physical literacy and physical activity of Iranian children
Authors: Mohammadi Majid , Elahipanah Farzaneh , Amani-shalamzari Sadegh 
Published: September 2023

Abstract
Background
The investigation of physical literacy (PL) and physical activity (PA) should be done in an ecological context because the socio-cultural situation can encourage or inhibit children’s activity. The present study aimed to study the role of the cultural environment in the development of PL and PA in Iranian children.

Methods
The statistical population consisted of Iranian children aged 8 to 12, of whom 270 students were recruited by cluster sampling from six provinces. They complete the Canadian Assessment of Physical Literacy 2 (CAPL-2) and the International Physical Activity Survey. To examine the cultural environment, the components of geographic location (west, south, central, east, and northwest), place of residence (downtown, suburban, and village), and gender (boys and girls) were used. A multivariate ANOVA analysis was used to analyze the data.

Results
From the geographic location, the findings showed that students inhabit in the west and east of Iran have significantly higher scores than their counterparts living in the central, south, and northwest at PA and PL (P < 0.001). From the place of residence, we observed a higher level of PA and PL in children living in the village than in those living in the suburbs and downtown (P < 0.001). In terms of gender, boys have higher PL and PA scores (P < 0.001).

Conclusion
The findings demonstrate that socio-cultural factors, geographic location, place of residence, and gender have different impacts on children’s PL and physical activity. Therefore, we suggest using ecologically appropriate decentralized planning in a physical education curriculum.
“Entre Nosotras:” a qualitative study of a peer-led PrEP project for transgender latinas
Authors: Zamudio-Haas Sophia , Koester Kim , Venegas Luz , Salinas Ariana , Herrera Cinthya , Gutierrez-Mock Luis , Welborn Layla , Deutsch Madeline B. , Sevelius Jae 
Published: September 2023

Abstract
Background
Uptake of HIV pre-exposure prophylaxis (PrEP) remains low among transgender people as compared to other subgroups, despite high rates of HIV acquisition. In California, Latinx people comprise 40% of the population and Latina transgender women experience some of the highest burden of HIV of any subgroup, indicating a critical need for appropriate services. With funding from the California HIV/AIDS Research Programs, this academic-community partnership developed, implemented, and evaluated a PrEP project that co-located HIV services with gender affirming care in a Federally Qualified Heath Center (FQHC). Trans and Latinx staff led intervention adaptation and activities.

Methods
This paper engages qualitative methods to describe how a PrEP demonstration project- Triunfo- successfully engaged Spanish-speaking transgender Latinas in services. We conducted 13 in-depth interviews with project participants and five interviews with providers and clinic staff. Interviews were conducted in Spanish or English. We conducted six months of ethnographic observation of intervention activities and recorded field notes. We conducted thematic analysis.

Results
Beneficial elements of the intervention centered around three intertwined themes: creating trusted space, providing comprehensive patient navigation, and offering social support “entre nosotras” (“between us women/girls”). The combination of these factors contributed to the intervention’s success supporting participants to initiate and persist on PrEP, many of whom had previously never received healthcare. Participants shared past experiences with transphobia and concerns around discrimination in a healthcare setting. Developing trust proved foundational to making participants feel welcome and “en casa/ at home” in the healthcare setting, which began from the moment participants entered the clinic and continued throughout their interactions with staff and providers. A gender affirming, bilingual clinician and peer health educators (PHE) played a critical part in intervention development, participant recruitment, and patient navigation.

Conclusions
Our research adds nuance to the existing literature on peer support services and navigation by profiling the multifaced roles that PHE served for participants. PHE proved instrumental to empowering participants to overcome structural and other barriers to healthcare, successfully engaging a group who previously avoided healthcare in clinical settings.
Oral phage therapy with microencapsulated phage A221 against Escherichia coli infections in weaned piglets
Authors: Mao Xinyu , Wu Yuxing , Ma Runwen , Li Lei , Wang Leping , Tan Yizhou , Li Ziyong , Liu Hui , Han Kaiou , Cao Yajie , Li Yinan , Peng Hao , Li Xun , Hu Chuanhuo , Wang Xiaoye 
Published: September 2023

Abstract
Background
Escherichia coli (E. coli) is a common pathogen that often causes diarrhea in piglets. Since bacteria are becoming more and more resistant to antibiotics, phages have become a promising alternative therapy. However, the therapy of oral phage often fails to achieve the desired effect. A novel phage named A221 was isolated by using E. coli GXXW-1103 as host strain, characterized by electron microscopy, genomic sequencing and analyzed by measuring lysis ability in vitro.

Results
Phage A221 was identified as a member of Ackermannviridae, Aglimvirinae, Agtrevirus with 153297 bp genome and effectively inhibited bacterial growth in vitro for 16 h. This study was conducted to evaluate the therapeutic effect of oral microencapsulated phage A221 on E. coli GXXW-1103 infections in weaned piglets. The protective effect of phage was evaluated by body weight analysis, bacterial load and histopathological changes. The results showed that with the treatment of phage A221, the body weight of piglets increased, the percentage of Enterobacteriaceae in duodenum decreased to 0.64%, the lesions in cecum and duodenum were alleviated, and the bacterial load in the jejunal lymph nodes, cecum and spleen were also significantly different with infected group (P < 0.001).

Conclusions
The results showed that phage A221 significantly increased the daily weight gain of piglets, reduced the bacterial load of tissues and the intestinal lesions, achieved the same therapeutic effect as antibiotic Florfenicol. Taken together, oral microencapsulated phage A221 has a good therapeutic effect on bacterial diarrhea of weaned piglets, which provides guidance for the clinical application of phage therapy in the future.