bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genome-wide association study reveals that epistasis underlies the pathogenicity of
Pectobacterium
Authors: Chen Changlong , Che Shu , Dong Zhou , Sui Jiayi , Tian Yu , Su Yanyan , Zhang Meng , Sun Wangwang , Fan Jiaqin , Xie Jianbo , Xie Hua 
Published: September 2023

ABSTRACT

Pectobacterium
spp. are important bacterial pathogens that cause soft rot symptoms in various crops. However, their mechanism of pathogenicity requires clarity to help control their infections. Here, genome-wide association studies (GWAS) were conducted by integrating genomic data and measurements of two phenotypes (virulence and cellulase activity) for 120 various
Pectobacterium
strains in order to identify the genetic basis of their pathogenicity. An artificial intelligence-based software program was developed to automatically measure lesion areas on Chinese cabbage, thereby facilitating accurate and rapid data collection for virulence phenotypes for use in GWAS analysis. The analysis discovered 428 and 158 loci significantly associated with
Pectobacterium
virulence (lesion area) and cellulase activity, respectively. In addition, 1,229 and 586 epistasis loci pairs were identified for the virulence and cellulase activity phenotypes, respectively. Among them, the AraC transcriptional regulator exerted epistasis effects with another three nutrient transport-related genes in pairs contributing to the virulence phenotype, and their epistatic effects were experimentally confirmed for one pair with knockout mutants of each single gene and double gene. This study consequently provides valuable insights into the genetic mechanism underlying
Pectobacterium
spp. pathogenicity.

Importance

Plant diseases and pests are responsible for the loss of up to 40% of food crops, and annual economic losses caused by plant diseases reach more than $220 billion. Fighting against plant diseases requires an understanding of the pathogenic mechanisms of pathogens. This study adopted an advanced approach using population genomics integrated with virulence-related phenotype data to investigate the genetic basis of
Pectobacterium
spp., which causes serious crop losses worldwide. An automated software program based on artificial intelligence was developed to measure the virulence phenotype (lesion area), which greatly facilitated this research. The analysis predicted key genomic loci that were highly associated with virulence phenotypes, exhibited epistasis effects, and were further confirmed as critical for virulence with mutant gene deletion experiments. The present study provides new insights into the genetic determinants associated with
Pectobacterium
pathogenicity and provides a valuable new software resource that can be adapted to improve plant infection measurements.
Control of
Helicobacter pylori
with engineered probiotics secreting selective guided antimicrobial peptides
Authors: Choudhury Ankan , Ortiz Patrick S. , Young Mikaeel , Mahmud Md. Toslim , Stoffel Ryan T. , Greathouse K. Leigh , Kearney Christopher M. 
Published: September 2023

ABSTRACT

Helicobacter pylori
is the primary cause of 78% of gastric cancer cases, providing an opportunity to prevent cancer by controlling a single bacterial pathogen within the complex gastric microbiota. We developed highly selective antimicrobial agents against
H. pylori
by fusing an
H. pylori
-binding guide peptide (MM1) to broad-spectrum antimicrobial peptides. The common dairy probiotic
Lactococcus lactis
was then engineered to secrete these guided antimicrobial peptides (gAMPs). When co-cultured
in vitro
with
H. pylori
, the gAMP probiotics lost no toxicity compared to unguided AMP probiotics against the target,
H. pylori
, while losing >90% of their toxicity against two tested off-target bacteria. To test binding to
H. pylori
, the MM1 guide was fused to green fluorescent protein (GFP), resulting in enhanced binding compared to unguided GFP as measured by flow cytometry. In contrast, MM1-GFP showed no increased binding over GFP against five different off-target bacteria. These highly selective gAMP probiotics were then tested by oral gavage in mice infected with
H. pylori
. As a therapy, the probiotics outperformed antibiotic treatment, effectively eliminating
H. pylori
in just 5 days, and also protected mice from challenge infection as a prophylactic. As expected, the gAMP probiotics were as toxic against
H. pylori
as the unguided AMP probiotics. However, a strong rebound in gastric species diversity was found with both the selective gAMP probiotics and the non-selective AMP probiotics. Eliminating the extreme microbial dysbiosis caused by
H. pylori
appeared to be the major factor in diversity recovery.

Importance

Alternatives to antibiotics in the control of
Helicobacter pylori
and the prevention of gastric cancer are needed. The high prevalence of
H. pylori
in the human population, the induction of microbial dysbiosis by antibiotics, and increasing antibiotic resistance call for a more sustainable approach. By selectively eliminating the pathogen and retaining the commensal community,
H. pylori
control may be achieved without adverse health outcomes. Antibiotics are typically used as a therapeutic post-infection, but a more targeted, less disruptive approach could be used as a long-term prophylactic against
H. pylori
or, by extension, against other gastrointestinal pathogens. Furthermore, the modular nature of the guided antimicrobial peptide (gAMP) technology allows for the substitution of different guides for different pathogens and the use of a cocktail of gAMPs to avoid the development of pathogen resistance.
Role of community-level emergency contraceptive pills awareness and possibilities of long-acting reversible or permanent methods in reducing unwanted births in Bangladesh: evidence from a nationwide cross-sectional survey
Authors: Rahman Md Mahabubur , Ferdous Zannatul , Ara Tasnim , Mahi Mahfuza , Haider M Moinuddin 
Published: September 2023

ObjectiveThis study aims to investigate the role of community-level emergency contraceptive pill (ECP) awareness in reducing unwanted births (UWBs) in Bangladesh and explore the regional variation in women’s appropriateness to adopt long-acting reversible contraceptives or permanent methods (LARCPMs) based on their child desire.Design, settings and participantsWe used data from the cross-sectional Bangladesh Demographic and Health Survey 2017–2018. We analysed the planning status of the last live birth 3 years preceding the survey of 20,127 ever-married women of reproductive age.MethodsConsidering women were nested within clusters, a mixed-effect multiple logistic regression was implemented to investigate the association between community-level ECP awareness and UWB by controlling for the effects of contextual, individual, and household characteristics.ResultsOnly 3.7% of women belonged to communities with high ECP awareness. At the national level, 2% of women had UWB. About 2.1% of women who resided in communities of low ECP awareness had UWB, while UWB was only 0.5% among women residing in high ECP awareness communities. The odds of UWB was 71% lower among women who resided in high ECP awareness communities than among those who resided in communities with low ECP awareness. However, community-level ECP awareness could not avert mistimed birth. Dhaka, Chattogram and Rangpur held the highest share of UWB. Fertility persisted for 89% of the women who wanted no more children. Among women who wanted no more children, 15% were not using any method, 13% used traditional family planning methods and only 13% adopted LARCPM. These women mostly resided in Dhaka, followed by Chattogram and Rajshahi.ConclusionThis study highlights the significant positive role of ECP awareness in reducing UWB in Bangladesh. Findings may inform policies aimed at increasing LARCPM adoption, particularly among women residing in Dhaka and Chattogram who want no more children.
Rehabilitation interventions for oculomotor deficits in adults with mild traumatic brain injury: a systematic review protocol
Authors: Biscardi Melissa , Grossinger Zane , Colantonio Angela , Bayley Mark , Mollayeva Tatyana 
Published: September 2023

IntroductionMild traumatic brain injury (mTBI) is the most common form of TBI with many individuals suffering from symptoms suggestive of deficits in oculomotor function. Although the symptoms are often experienced transiently, almost 50% of individuals will experience persistent symptoms. Oculomotor deficits can last months after injury and decrease function and the ability to participate in work, school and sport. To date, rehabilitation interventions targeting oculomotor deficits in mTBI have been reported on in several studies with varying study designs; however, the effectiveness of these interventions on measures of oculomotor function has not been established. The purpose of this paper is to present a protocol for a systematic review that aims to examine the effectiveness of rehabilitation interventions for improving function in adults with oculomotor deficits after mTBI.Methods and analysisSystematic searches in Medline Ovid, EMBASE, PsycINFO, CINAHL and Scopus will be conducted to identify experimental studies published in English from each databases inception date to present, involving adult patients with mTBI and oculomotor deficits. Citations will be saved and managed in EndNote V.20. Two independent reviewers will identify eligible studies and perform data abstraction. Any discrepancies will be solved by discussion, and a third reviewer will be consulted if necessary. A meta-analysis will be conducted for outcomes reported in two or more studies. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines will be followed for reporting.Ethics and disseminationThis study does not involve primary data collection; therefore, formal ethical approval by an institutional review board is not required. Final results will be disseminated through open-access peer-reviewed publications. Abstracts will be presented at suitable national and international conferences or workshops. Furthermore, important information will be shared with clinical authorities, clinicians and at affiliated research institution-based websites and relevant servers.PROSPERO registration numberCRD42022352276.
General practitioner residents’ experiences and perceptions of outpatient training in primary care settings in China: a qualitative study
Authors: Wu Lingyan , Tong Yuling , Yu Yingying , Yu Xinyan , Zhou Yening , Xu Meiqun , Guo Yi , Song Zhenya , Xu Zhijie 
Published: September 2023

ObjectivesThe implementation of outpatient training in primary care settings is an essential part of residency training for general practitioner (GP) residents. However, limited research exists on their experiences and perceptions of this training. This study aimed to explore the experiences and perceptions of GP residents regarding outpatient training in primary care settings in China and provide insights and recommendations to enhance training quality.DesignA qualitative descriptive study employing in-depth interviews.SettingTwo community healthcare centres (CHCs) that implement outpatient training programmes for GP residents in Zhejiang Province, China.ParticipantsIn total, 20 GP residents affiliated with 14 CHCs and two hospitals across Zhejiang Province and Guizhou Province who had completed outpatient training in either CHC for over 1 month.ResultsOf the 20 participants in this study, 11 (55%) were women, and the mean age was 28 years. GP residents completed the process of consultation, physical examination and therapy independently; subsequently, the community preceptors provided feedback based on their clinical performance and modelled their clinical skills. The benefits perceived by GP residents included improved clinical skills and confidence in practice, and they learned approaches to maintaining good relationships with patients. They preferred dealing with complex cases, discussions with peers and the indirect supervision of community preceptors in the training session. Residents recommended that measures be taken to improve the training quality regarding patient selection and recruitment, clinical skills in the training session, and assessment of clinical performance.ConclusionsThe outpatient training in primary care settings provides constructive opportunities for GP residents to improve their professional competencies. Although the current training sessions and the abilities of community preceptors largely satisfy the needs of GP residents, further research is needed to evaluate the effectiveness of training and explore approaches to improve its quality.
Antenatal and early childhood exposures associated with non-fatal infant injury: evidence from a longitudinal birth cohort in New Zealand
Authors: Ghebreab Luam , Kool Bridget , Lee Arier , Morton Susan 
Published: September 2023

ObjectiveTo identify antenatal and early childhood exposures of unintentional injury among infants in New Zealand (NZ).MethodThe theoretical life-course framework of child injury prevention domains was utilised to analyse data from a prospective longitudinal NZ birth cohort (Growing Up in NZ). Risk and protective factors for injury were identified using Robust Poisson regression models.ResultAmong children included for the analysis(n=6304), 52% were male, 55% were born to European mothers, and 37% lived in a household with high levels of deprivation. Mothers reported that 6% of infants (n=406) had sustained at least one injury by 9 months. Multivariate analysis showed injury risk among single mothers with antenatal depression were more than twice that (IRR=2.20) of children of mothers with partners and without depression.ConclusionUnderstanding antenatal risk and protective factors for infant injury will assist in implementing injury prevention programmes or modifying the existing policies that affect these vulnerable age groups.
High glycemia and resistin normalized in children with double burden of malnutrition: a cross-sectional study
Authors: Pereira Joicy Karla Grangeiro , de Moraes Rúbia Cartaxo Squizato , Sawaya Ana Lydia , Alves José Luiz de Brito , Filgueiras Andrea Rocha , Franco Maria do Carmo Pinho , Martins Vinicius José Baccin 
Published: September 2023

The coexistence of stunting and excess weight in the same individual is defined as a double burden of malnutrition (DBM) and is associated with noncommunicable diseases. In this study, we evaluated the impact of DBM on adipokine concentrations and metabolic profiles in children compared with weight excess alone. Children were allocated to the weight excess group ( n = 23) (height-for-age (HAZ) > 0.0 and < 2.0 Z-score and body mass index-for-age (BMI/A) > 1.0 Z-score) or DBM ( n = 22) group (HAZ < −1.0 Z-score (including mild stunting) and BMI/A > 1.0 Z-score). Lipid, glycemic profile, resistin, plasminogen activator inhibitor-1, leptin, and adiponectin concentrations were analyzed. Glycemia was significantly higher in the DBM group compared to the weight excess group (5.05 (4.76–5.31) mmol/L vs. 4.57 (4.35–4.81) mmol/L), although no differences were found in insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Adipokine concentrations did not differ between the groups. However, the DBM group showed higher resistin concentrations normalized by body fat mass than those of the weight excess group (1.44 (0.98–1.93) ng/mL vs. 0.76 (0.55–1.45) ng/mL). Insulin and HOMA-IR showed a negative correlation with adiponectin ( r = −0.590 and −0.624, respectively, both p < 0.01). DBM was associated with increased glucose and resistin concentrations adjusted by fat mass compared to that associated with excess weight alone. Therefore, this association between mild stunting and weight excess has deleterious potential for long-term metabolic function, highlighting an additional precaution against weight gain in children, especially in those with stunting.
Flows Over Rotating Disks and Cones
Authors: Alfredsson P. Henrik , Kato Kentaro , Lingwood R.J. 
Published: September 2023

Rotating-disk flows were first considered by von Kármán in a seminal paper in 1921, where boundary layers in general were discussed and, in two of the nine sections, results for the laminar and turbulent boundary layers over a rotating disk were presented. It was not until in 1955 that flow visualization discovered the existence of stationary cross-flow vortices on the disk prior to the transition to turbulence. The rotating disk can be seen as a special case of rotating cones, and recent research has shown that broad cones behave similarly to disks, whereas sharp cones are susceptible to a different type of instability. Here, we provide a review of the major developments since von Kármán's work from 100 years ago, regarding instability, transition, and turbulence in the boundary layers, and we include some analysis not previously published.
Data from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim. , Lang Jinyi , Wang Guihua , Xu Chuan 
Published: September 2023

<div>Abstract<p>Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of ESCC patients to NACI. Intra-tumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing (scRNA-seq) demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ Treg cells. Mice that underwent fecal microbial transplantation (FMT) or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. </p></div>
EGFR Inhibition Overcomes Resistance to FGFR4 Inhibition and Potentiates FGFR4 Inhibitor Therapy in Hepatocellular Carcinoma
Authors: Shen Bin , Shi Jue-Ping , Zhu Zhi-Xuan , He Zhi-Dong , Liu Shen-Yan , Shi Wan , Zhang Yong-Xian , Ying Hai-Yan , Wang Jie , Xu Rui-Feng , Fang Fei , Chang Harrison Xuesong , Chen Zhui , Zhang Nan-Nan 
Published: September 2023

Abstract
Aberrant activation of the FGF19-FGFR4 signaling pathway plays an essential role in the tumorigenesis of hepatocellular carcinoma (HCC). As such, FGFR4 inhibition has emerged as a novel therapeutic option for the treatment of HCC and has shown preliminary efficacy in recent clinical trials for patients exhibiting aberrant FGF19 expression. Resistance to kinase inhibitors is common in oncology, presenting a major challenge in the clinical treatment process. Hence, we investigated the potential mechanisms mediating and causing resistance to FGFR4 inhibition in HCC. Upon the successful establishment of a battery of cellular models developing resistance to FGFR4 inhibitors, we have identified the activation of EGFR, MAPK, and AKT signaling as the primary mechanisms mediating the acquired resistance. Combination of inhibitors against EGFR or its downstream components restored sensitivity to FGFR4 inhibitors. In parental HCC cell lines, EGF treatment also resulted in resistance to FGFR4 inhibitors. This resistance was effectively reverted by inhibitors of the EGFR signaling pathway, suggesting that EGFR activation is a potential cause of intrinsic resistance. We further confirmed the above findings in vivo in mouse xenograft tumor models. Genomic analysis of patient samples from The Cancer Genome Atlas confirmed that a segment of patients with HCC harboring FGF19 overexpression indeed exhibited increased activation of EGFR signaling. These findings conclusively indicate that both induced and innate activation of EGFR could mediate resistance to FGFR4 inhibition, suggesting that dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for the treatment of FGF19-FGFR4 altered HCC.
The reliability and validity of the cone evasion walk test in patients with hip osteoarthritis
Authors: Sevik Kacmaz Kevser , Unver Bayram , Karatosun Vasfi 
Published: September 2023

Background: Hip osteoarthritis (OA) can result in joint pain, stiffness, compromised balance, hindered mobility, and decreased functional independence. The Cone Evasion Walk Test (CEW) was designed for evaluating balance by evaluating the capacity to evade obstacles. Consequently, the study’s objective was to assess the validity and reliability of the CEW in hip OA patients. Methods: A total of 24 patients with hip OA were enrolled. Patients performed trials for the CEW and the timed up and go test (TUG). Between the trials, patients rested for an hour. The falls within the previous 12-month period were reported. Results: The analysis showed that the CEW has excellent reliability and high validity in hip OA. ( p < 0.001). The relative (intraclass correlation [ICC] coefficient) and absolute (SEM and SRD95) reliability of the CEW were 0.96 (0.88–0.98 95% CI), 0.56, and 1.54, respectively. The Spearman correlation coefficient between the CEW and the TUG was 0.74 ( p < 0.001) and between the CEW and the falls in the last 12 months was 0.51 ( p > 0.05). Conclusions: The CEW is effective for evaluating the function, dynamic balance, and mobility in patients with hip OA and could be a more accurate measure of the dynamic balance activities in the community.
Modelling the rate of trainees transitioning to Fellowship before achieving competence under the RANZCP’s Alternative Assessment Pathway to the Objective Structured Clinical Examination
Authors: Amos Andrew , Weightman Michael James , Miller Edward 
Published: September 2023

Objective The Objective Structured Clinical Examination (OSCE) has been removed from the Royal Australian and New Zealand College of Psychiatrists’ (RANZCP) training pathway. This decision occurred in the context of an Alternative Assessment Pathway (AAP) necessitated by Covid-19, justified by logistical, methodological and equity concerns. The false positive rate of trainees progressing to Fellowship before achieving competence is a key indicator for evaluating any assessment leading to psychiatric Fellowship. Variations in the statistical properties of the AAP and OSCE were analysed for their impact on pre-competent trainees progressing to Fellowship. Method Starting with the false positive scenario presented to justify discontinuing the OSCE, false positive rates associated with the AAP and OSCE were calculated based on different assumptions about reliability and accuracy. Results The analyses suggest that less reliable and less accurate alternatives to the OSCE, such as the AAP, increase the number of pre-competent trainees progressing to Fellowship. Conclusions Given possible increases in pre-competent trainees progressing to Fellowship while alternatives to the OSCE are finalised, confidence in the RANZCP's training program demands robust public analyses of those alternatives.