bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
Authors: Alemany Silvia , Soler-Artigas María , Cabana-Domínguez Judit , Fakhreddine Dana , Llonga Natalia , Vilar-Ribó Laura , Rodríguez-Urrutia Amanda , Palacio Judit , González-Castro Ana María , Lobo Beatriz , Alonso-Cotoner Carmen , Simrén Magnus , Santos Javier , Ramos-Quiroga Josep Antoni , Ribasés Marta 
Published: April 2023

Abstract
Background
Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.

Methods
We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.

Results
IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.

Conclusions
These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
Vaccination with recombinant Lactococcus lactis expressing HA1-IgY Fc fusion protein provides protective mucosal immunity against H9N2 avian influenza virus in chickens
Authors: Zhang Ruihua , Xu Tong , Li Ziping , Li Longfei , Li Chunhong , Li Xinrui , Wang Zhiyue , Wang Shaohua , Wang Xuejing , Zhang Hongliang 
Published: April 2023

Abstract
Background
H9N2 virus is mainly transmitted through the respiratory mucosal pathway, so mucosal immunity is considered to play a good role in controlling avian influenza infection. It is commonly accepted that no adequate mucosal immunity is achieved by inactivated vaccines, which was widely used to prevent and control avian influenza virus infection. Thus, an improved vaccine to induce both mucosal immunity and systemic immunity is urgently required to control H9N2 avian influenza outbreaks in poultry farms.

Methods
In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the HA1 proteins derived from an endemic H9N2 virus strain and chicken IgY Fc fragment. We evaluated the immunogenicity and protective efficacy of this recombinant L. lactis HA1-Fc strain.

Results
Our data demonstrated that chickens immunized with L. lactis HA1-Fc strain showed significantly increased levels of serum antibodies, mucosal secretory IgA, T cell-mediated immune responses, and lymphocyte proliferation. Furthermore, following challenge with H9N2 avian influenza virus, chickens immunized with L. lactis HA1-Fc strain showed reduced the weight loss, relieved clinical symptoms, and decreased the viral titers and the pathological damage in the lung. Moreover, oropharyngeal and cloacal shedding of the H9N2 influenza virus was detected in chicken immunized with L. lactis HA1-Fc after infection, the results showed the titer was low and reduced quickly to reach undetectable levels at 7 days after infection.

Conclusion
Our data showed that the recombinant L. lactis HA1-Fc strain could induce protective mucosal and systemic immunity, and this study provides a theoretical basis for improving immune responses to prevent and control H9N2 virus infection.
The role of doulas in providing breastfeeding support during the COVID-19 pandemic
Authors: Ochapa Monica , Baptiste-Roberts Kesha , Barrett Sharon E. , Animasahun Adeola , Bronner Yvonne 
Published: April 2023

Abstract
Background
Doulas have been instrumental in providing breastfeeding support to nursing mothers before and during the COVID-19 pandemic, as they can significantly impact a mother's ability to initiate and maintain breastfeeding. However, the COVID-19 pandemic, subsequent lockdowns, and social isolation created challenges for nursing mothers to access doulas' services, usually provided in person. In this study, we examined the role of doulas in providing breastfeeding support during the COVID-19 pandemic, exploring adaptation to COVID-19 guidelines and the challenges doulas face in providing breastfeeding support during the pandemic.

Methods
A systematic review was conducted following the PRISMA guidelines. Thirteen scientific databases and twenty peer-reviewed journals were searched for journal articles published in English between January 2020 and March 2022 using key search terms (e.g., Doula, Breastfeeding, COVID-19). Studies evaluating the role of doulas in providing breastfeeding support during COVID-19, and the impact of COVID-19 Guidelines on doula services, were included. Two reviewers independently performed the risk of bias assessment and data extraction. Summative content analysis was used to analyze the data.

Results
The majority of studies were conducted in developed nations. This systematic review includes eight articles, four qualitative, one survey, two mixed-methods studies, and one prospective research study. Seven of the eight studies were conducted in the United States, and the eighth was conducted in multiple countries. These studies have three main themes: (1) virtual breastfeeding support provided by doulas during the pandemic; (2) remote social support provided by doulas to breastfeeding mothers during the pandemic; and (3) barriers to doula service delivery due to COVID-19 restrictions, primarily the exclusion of doulas as essential workers. The eight studies showed that doulas found innovative ways to serve the needs of birthing and nursing mothers during the difficulties brought on by the pandemic.

Conclusion
Doulas provided breastfeeding support during the COVID-19 pandemic by utilizing innovative service delivery methods while navigating changes in COVID-19 guidance. However, system-level integration of doulas' work and the acknowledgment of doulas as essential healthcare providers are needed to enhance doula service delivery capacity, especially during a pandemic, to help improve maternal health outcomes.
Short and mid-term effects of modified release technique in rheumatic mitral valve repair
Authors: Chong Hoshun , Gao Yaxuan , Xue Yunxing , Zhu Xiyu , Li Jie , Wang Junxia , Zhang He , Wang Dongjin , Cao Hailong 
Published: April 2023

Abstract
Objective
Repair or replacement remains debatable in rheumatic heart disease. To regain optimal mean transvalvular pressure gradients and end-diastolic peak flow velocity, the modified release technique combined peeling in the anterior leaflet and separated the shortened chordal. In the end, the short and mid-term outcomes of the modified release technique were evaluated.

Methods
We retrospectively analyzed a series of 128 patients with rheumatic mitral stenosis, from January 2018 to July 2021 in our center. All patients undergoing mitral valve repair were using the modified release technique. The effect of mitral valve repair was evaluated by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography.

Results
All the 128 patients successfully repaired the mitral valve. The intraoperative transesophageal echocardiography showed trivial or mild regurgitation. The aortic valve was repaired without obvious regurgitation in 12 cases, 5 cases received an aortic valve replacement, 89 cases underwent tricuspid annuloplasty. There were no blood transfusions in most patients, no deaths nor complications during peri-operation, also, no deaths and adverse events were observed during the follow-up period from 3 to 42 months. During the follow-up, 122 cases had no mitral valve regurgitation and 2 cases of moderate regurgitation, 4 cases of mild to moderate regurgitation. The mean peak flow velocity was 1.2 ± 0.3 m / s, no new-onset stenosis occurred.

Conclusion
Modified release technique is safe and feasible. Its durability is acceptable in the short and mid-term, with no new-onset stenosis during the follow-up.
Therapist competencies in the context of group-based exercise programs in medical rehabilitation: a qualitative study with patients and exercise therapists from Germany
Authors: Schuber André Arik , Gernert Madeleine , Schaller Andrea 
Published: April 2023

Abstract
Background
Group-based exercise programs account for nearly half of exercise therapy services provided in German medical rehabilitation facilities. However, information about necessary therapist competencies for the successful execution of these programs is sparse. Thus, the aim of this qualitative study was to explore relevant therapist competencies in the context of group-based exercise programs from the patients’ and therapists’ perspective.

Methods
Semi-structured interviews were conducted with five rehabilitation patients following a 3-week inpatient orthopedic rehabilitation program as well as five exercise therapists with work experience in group-based exercise therapy. Data were analyzed using structuring content analysis according to Kuckartz.

Results
From 155 topic-related text passages, collected over 10 interviews, four competency categories with 16 subcategories and respective characteristics were identified. In addition to professional expertise like biomedical knowledge, exercise therapists were expected to possess a multitude of didactic-methodological, personal, and social-communicative abilities.

Conclusion
Our results suggest that the psychosocial, behavioral and educational goals of group-based exercise programs necessitate a wide range of therapist competencies. These conform to the multidimensional nature of exercise therapy and should therefore be covered in vocational and continuing education.
Stable frequency transfer for clock synchronization for telecom networks
Authors: Wang Xiaocheng , Han Qiaoni , Li Yupeng , Han Liang 
Published: April 2023

AbstractA stable and reliable clock synchronization system that transfers reference clocks to nodes is essential for telecom networks. Mainly, the clock synchronization of telecom networks is carried out through satellite links. However, for the evolving ubiquitous wireless communications, especially in some harsh environments, such as underground and trenches, the satellite-based clock synchronization scheme bears inevitable obstacles, which may cause strategic risks for the telecom networks, since no control and manipulation can be imposed on the satellite systems. Therefore, to ensure the robust operation of telecom networks with performance guarantees, some auxiliary means are desirable to assist clock synchronization that is solely based on satellite links. In this article, we report a phase-stabilized frequency signal transmission on branching optical fiber for clock synchronization for telecom networks. Particularly, the phase fluctuation due to optical carriers separation link and fiber link is compensated by a feedback network, which employs a high-precision voltage-controlled oscillator in the phase-locked loop to drive the acousto-optic frequency shifter for fast phase correction. Furtherly, the factors that cause performance limitations of the frequency distribution system are analyzed. Eventually, the experiment results obtained show that a stabilized fiber-optic frequency transfer scheme can be used as a reliable method for clock synchronization with high accuracy.
The X-factor in ART: does the use of assisted reproductive technologies influence DNA methylation on the X chromosome?
Authors: Romanowska Julia , Nustad Haakon E. , Page Christian M. , Denault William R. P. , Lee Yunsung , Magnus Maria C. , Haftorn Kristine L. , Gjerdevik Miriam , Novakovic Boris , Saffery Richard , Gjessing Håkon K. , Lyle Robert , Magnus Per , Håberg Siri E. , Jugessur Astanand 
Published: April 2023

Abstract
Background
Assisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother–father–newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa). To verify our results from the MoBa cohort, we used an external cohort of 149 ART and 58 non-ART neonates from the Australian ‘Clinical review of the Health of adults conceived following Assisted Reproductive Technologies’ (CHART) study. The Illumina EPIC array was used to measure DNAm in both datasets. In the MoBa cohort, we performed a set of X-chromosome-wide association studies (‘XWASs’ hereafter) to search for sex-specific DNAm differences between ART and non-ART newborns. We tested several models to investigate the influence of various confounders, including parental DNAm. We also searched for differentially methylated regions (DMRs) and regions of co-methylation flanking the most significant CpGs. Additionally, we ran an analogous model to our main model on the external CHART dataset.

Results
In the MoBa cohort, we found more differentially methylated CpGs and DMRs in girls than boys. Most of the associations persisted after controlling for parental DNAm and other confounders. Many of the significant CpGs and DMRs were in gene-promoter regions, and several of the genes linked to these CpGs are expressed in tissues relevant for both ART and sex (testis, placenta, and fallopian tube). We found no support for parental DNAm-dependent features as an explanation for the observed associations in the newborns. The most significant CpG in the boys-only analysis was in UBE2DNL, which is expressed in testes but with unknown function. The most significant CpGs in the girls-only analysis were in EIF2S3 and AMOT. These three loci also displayed differential DNAm in the CHART cohort.

Conclusions
Genes that co-localized with the significant CpGs and DMRs associated with ART are implicated in several key biological processes (e.g., neurodevelopment) and disorders (e.g., intellectual disability and autism). These connections are particularly compelling in light of previous findings indicating that neurodevelopmental outcomes differ in ART-conceived children compared to those naturally conceived.
Cardiotoxicity of chloroquine and hydroxychloroquine through mitochondrial pathway
Authors: Seydi Enayatollah , Hassani Mozhgan Karbalaei , Naderpour Saghi , Arjmand Abdollah , Pourahmad Jalal 
Published: April 2023

Abstract
Background
Medical therapies can cause cardiotoxicity. Chloroquine (QC) and hydroxychloroquine (HQC) are drugs used in the treatment of malaria and skin and rheumatic disorders. These drugs were considered to help treatment of coronavirus disease (COVID-19) in 2019. Despite the low cost and availability of QC and HQC, reports indicate that this class of drugs can cause cardiotoxicity. The mechanism of this event is not well known, but evidence shows that QC and HQC can cause cardiotoxicity by affecting mitochondria and lysosomes.

Methods
Therefore, our study was designed to investigate the effects of QC and HQC on heart mitochondria. In order to achieve this aim, mitochondrial function, reactive oxygen species (ROS) level, mitochondrial membrane disruption, and cytochrome c release in heart mitochondria were evaluated. Statistical significance was determined using the one-way and two-way analysis of variance (ANOVA) followed by post hoc Tukey to evaluate mitochondrial succinate dehydrogenase (SDH) activity and cytochrome c release, and Bonferroni test to evaluate the ROS level, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling.

Results
Based on ANOVA analysis (one-way), the results of mitochondrial SDH activity showed that the IC50 concentration for CQ is 20 µM and for HCQ is 50 µM. Based on two-way ANOVA analysis, the highest effect of CQ and HCQ on the generation of ROS, collapse in the MMP, and mitochondrial swelling were observed at 40 µM and 100 µM concentrations, respectively (p < 0.05). Also, the highest effect of these two drugs has been observed in 60 min (p < 0.05). The statistical results showed that compared to CQ, HCQ is able to cause the release of cytochrome c from mitochondria in all applied concentrations (p < 0.05).

Conclusions
The results suggest that QC and HQC can cause cardiotoxicity which can lead to heart disorders through oxidative stress and disfunction of heart mitochondria.
Metapangenomics of wild and cultivated banana microbiome reveals a plethora of host-associated protective functions
Authors: Singh Simrandeep , Aghdam Shiva A. , Lahowetz Rachel M. , Brown Amanda M. V. 
Published: April 2023

Abstract
Background
Microbiomes are critical to plants, promoting growth, elevating stress tolerance, and expanding the plant’s metabolic repertoire with novel defense pathways. However, generally microbiomes within plant tissues, which intimately interact with their hosts, remain poorly characterized. These endospheres have become a focus in banana (Musa spp.)—an important plant for study of microbiome-based disease protection. Banana is important to global food security, while also being critically threatened by pandemic diseases. Domestication and clonal propagation are thought to have depleted protective microbiomes, whereas wild relatives may hold promise for new microbiome-based biological controls. The goal was to compare metapangenomes enriched from 7 Musa genotypes, including wild and cultivated varieties grown in sympatry, to assess the host associations with root and leaf endosphere functional profiles.

Results
Density gradients successfully generated culture-free microbial enrichment, dominated by bacteria, with all together 24,325 species or strains distinguished, and 1.7 million metagenomic scaffolds harboring 559,108 predicted gene clusters. About 20% of sequence reads did not match any taxon databases and ~ 62% of gene clusters could not be annotated to function. Most taxa and gene clusters were unshared between Musa genotypes. Root and corm tissues had significantly richer endosphere communities that were significantly different from leaf communities. Agrobacterium and Rhizobium were the most abundant in all samples while Chitinophagia and Actinomycetia were more abundant in roots and Flavobacteria in leaves. At the bacterial strain level, there were > 2000 taxa unique to each of M. acuminata (AAA genotype) and M. balbisiana (B-genotype), with the latter ‘wild’ relatives having richer taxa and functions. Gene ontology functional enrichment showed core beneficial functions aligned with those of other plants but also many specialized prospective beneficial functions not reported previously. Some gene clusters with plant-protective functions showed signatures of phylosymbiosis, suggesting long-standing associations or heritable microbiomes in Musa.

Conclusions
Metapangenomics revealed key taxa and protective functions that appeared to be driven by genotype, perhaps contributing to host resistance differences. The recovery of rich novel taxa and gene clusters provides a baseline dataset for future experiments in planta or in vivo bacterization or engineering of wild host endophytes.
Food Provision at the Olympic Games in the New Millennium: A Meta-narrative Review
Authors: Pelly Fiona E. , Tweedie Judith , O’Connor Helen 
Published: April 2023

Abstract
Background and objective
The objective of this meta-narrative review was to identify, organise and map the literature on food provision and nutrition support at the summer and winter Olympic and Paralympic Games (OPG) and similar major competition events over the past 21 years. This builds on a comprehensive update of a previous historical review of the evolution of food provision at the summer Olympic Games up until 2000 and considers contemporary issues such as the global pandemic and sustainability goals.

Methods
A range of sources included primary research and review articles, edited book chapters, theses, conference papers or abstracts, International Olympic Committee reports, Organising Committees’ food vision and post-Games reports, independent professional reports, and media and periodicals including magazines and trade journals. The search strategy included four steps: a database search that complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews criteria, a search of the Olympic Studies Centre, a review of reference lists for unpublished sources, and a Google search for additional media reports. The researchers followed an iterative process where emerging narratives were discussed, recorded and refined as data were extracted.

Results
The data from 229 records were extracted into a spreadsheet and grouped according to the type of evidence and specific event, then presented chronologically to give a perspective on the development of food provision and nutrition support. Eleven narratives emerged from the data extraction: ‘description of meals, menus and food’, ‘vision of the food provision’, ‘food safety’, ‘catering company involvement’, ‘sponsorship or contracts with food companies’, ‘athlete perspective’, ‘stakeholder perspective’, ‘athlete food intake,’ ‘nutrition input in food provision’, ‘food environment’ and ‘sustainability’.

Conclusion
Results suggest that athletes' dining expectations, organising committee budgets, expert input and current global trends have led to food delivery changes. The OPG food environment has the capacity to positively influence the dietary choices of athletes and teams, while evolving to meet contemporary global challenges such as COVID-19 and sustainability targets.