bluuebunny/crossref_metadata_2025_split huggingface dataset:
Core values and principles of general practice and family medicine: perspectives of German GP residents—a cross-sectional study
Authors: Dreher Andreas Christian , Ko Jonathan , Becker Christine , Bischoff Martina , Förster Christian , Jähnig Tanja , Stengel Sandra , Altiner Attila , Schwill Simon 
Published: February 2025

BackgroundThe core values and principles of general practice (GP) and family medicine (FM) have been described by various international scientific societies, including the World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (WONCA). These values and principles, such as continuity of care, a bio-psycho-social approach, and hermeneutic case understanding, are also integrated into FM training programs. The aim of this study was to investigate the knowledge and perspectives of FM trainees regarding the core values and principles of FM.MethodsIn a cross-sectional study, new participants of the postgraduate FM training program KWBW Verbundweiterbildung plus© were asked to complete a self-developed questionnaire on their educational experiences, attitudes toward, and knowledge of core values in GP/FM. Specifically, participants were asked to identify the core values and principles associated with GP/FM. Qualitative analysis was used to explore the answers. Additionally, participants were required to define a set of core values, which were then analyzed semi-quantitatively and rated as correct, semi-correct, wrong, or unknown.ResultsOut of a total of n = 303 trainees, n = 250 completed the questionnaire. The majority (n = 194) were in their third year of training. A third of the participants reported having studied core values in the past. The participants identified several core values and principles associated with GP/FM. The practical relevance and confirmation of becoming an FM doctor were well-evaluated.ConclusionThe study identified deficits in the active and passive knowledge of GP/FM core values among GP residents. An educational compact intervention about GP/GM core principles and values proved successful in its realization and implementation. To become a reflective practitioner in FM, GP residents must engage in self-reflection on evidence-based medicine, attitudes, core values, and principles. Therefore, core values should be addressed at the beginning of FM training and constantly referred to within the longitudinal curriculum. Family physicians should be continuously empowered to explicitly reflect on and discuss the core principles that shape their professional identity.
mpt64 mutations in Mycobacterium tuberculosis with negative MPT64 antigen assay results from a tertiary hospital in Southeastern China
Authors: Pan Xinling , Zhou Sujuan , Jin Lulu , Ji Songjun , Lou Xingxing , Lu Bin , Zhao Jin 
Published: February 2025

BackgroundMPT64 protein is an effective marker for detecting Mycobacterium tuberculosis (MTB) in liquid culture and clinical tissue samples. However, some MTB clinical isolates test negative for this antigen because of varied mutation types across different regions.MethodsDNA samples of MPT64 antigen assay-negative MTB strains were collected from a tertiary hospital from January 2016 to January 2024, and mpt64 gene mutations were detected by sequencing. Clinical records of patients with negative MPT64 antigen results were collected and compared with those of patients with positive results. The global distribution of mpt64 gene mutations was analyzed using MTB genome sequences from the National Center for Biotechnology Information (NCBI) database.ResultsAmong 821 mycobacterial specimens with negative MPT64 antigen assay results, 77 MTB strains were collected from 73 patients. Compared with MPT64-positive patients (n = 301), a higher percentage of MPT64-negative patients had a history of anti-tuberculosis therapy (n = 7, 11.1%; P = 0.01). Moreover, MPT64-negative patients demonstrated a lower percentage of positive Gene Xpert results than MPT64-positive patients (73.8% vs 95.1%, P &lt; 0.001). Several gene mutations were detected in the MPT64-negative MTB strains, including 63 bp deletion, single nucleotide mutations, and IS6110 insertion. Among 7,324 MTB genomes from the NCBI database, 87 strains had mutations in the mpt64 gene sequence, with four common mutation sites causing single amino acid changes, including G34A (8.0%), A103G (27.6%), T128A (9.2%), and C477A (24.1%).ConclusionA negative MPT64 antigen result in MTB cultures can be attributed to mutations in the mpt64 gene, and infections caused by these strains are more likely to be misdiagnosed.
Genomic analysis of multidrug-resistant Escherichia coli isolated from dairy cows in Shihezi city, Xinjiang, China
Authors: Bello Abdullahi , Ning Siqi , Zhang Qi , Ni Wei , Hu Shengwei 
Published: February 2025

IntroductionDairy farming plays a vital role in agriculture and nutrition; however, the emergence of antimicrobial resistance (AMR) among bacterial pathogens poses significant risks to public health and animal welfare. Multidrug-resistant (MDR) Escherichia coli strains are of particular concern due to their potential for zoonotic transmission and resistance to multiple antibiotics. In this study, we investigated the prevalence of AMR and analyzed the genomes of two MDR E. coli isolated from dairy cows in Shihezi City.MethodsFecal samples were collected from dairy cows, and E. coli strains were isolated. Antibiotic susceptibility testing was conducted using the Kirby-Bauer disk diffusion method against 14 antibiotics. Two MDR isolates (E.coli_30 and E.coli_45) were selected for whole-genome sequencing and comparative genomic analysis. The Comprehensive Antibiotic Resistance Database (CARD) was used to identify AMR genes, and virulence factors were analyzed. Phylogenetic analysis was performed to determine the evolutionary relationships of the isolates, and a pangenome analysis of 50 E. coli strains was conducted to assess genetic diversity. The presence of mobile genetic elements (MGEs), including insertion sequences (IS) and transposons, was also examined.ResultsAmong the E. coli isolates, 22.9% exhibited MDR, with high resistance to imipenem and ciprofloxacin, while gentamicin and tetracycline remained the most effective antibiotics. Genomic analysis revealed key AMR genes, including mphA, qnrS1, and blaCTX-M-55 (the latter found only in E.coli_45), conferring resistance to macrolides, quinolones, and beta-lactams, respectively. Virulence genes encoding type III secretion systems (TTSS) and adhesion factors were identified, indicating pathogenic potential. Phylogenetic analysis showed that E.coli_30 and E.coli_45 originated from distinct ancestral lineages. The presence of two extended-spectrum β-lactamase (ESBL) genes in E.coli_45 was noticeable, so we studied their global and national distribution using evolutionary analysis. We found that they are endemic in E. coli, Salmonella enterica, and Klebsiella pneumoniae. Pangenome analysis revealed significant genetic diversity among E. coli strains, with unique genes related to metabolism and stress response. This indicates the bacteria’s adaptation to various environments. MGEs were identified as key contributors to genetic variability and adaptation.DiscussionThis study highlights the growing threat of MDR E. coli in dairy farms, emphasizing the critical role of MGEs in the spread of resistance genes. The genetic diversity observed suggests strong adaptive capabilities, justifying the need for continuous AMR surveillance in livestock. Effective monitoring and mitigation strategies are essential to prevent the dissemination of MDR bacteria, thereby protecting both animal and public health.
Genomic identification of a pair of multidrug-resistant but non-pathogenic Salmonella enterica serovar Goldcoast isolates in southeast China
Authors: Yuan Yongjuan , Li Ping , Shen Wei , Li Min , He Xiaofei , Zhou Bin 
Published: February 2025

IntroductionSalmonella is an important foodborne pathogen that can induce severe diseases such as gastrointestinal disease and typhoid fever. Accumulating evidence revealed that Salmonella’s resistance to antibiotics also seriously affects human health. Pathogenic Salmonella enterica serovar Goldcoast (S. Goldcoast) was first detected in 2010 in China and was predicted to have an increasing tendency.MethodsThe MacConkey agar, Salmonella Shigella agar, three-sugar iron agar slant, and Gram-stained microscopic examination were used for strain identification. Gram-negative bacteria identification cards explored more properties of the isolates, while antimicrobial susceptibility testing was used to examine the multidrug resistance. The 2nd and 3rd generation sequencing revealed the genetic information of the isolates.ResultsTwo non-pathogenic isolates with multidrug resistance, JS33 and JS34, harbored 42 antibiotic-resistant genes (ARGs) in contig1 and 13 ARGs in contig2, were isolated from a healthy donor living in southeast China and identified as S. Goldcoast (6,8:r:l,w). Interestingly, JS33 and JS34 showed identical responses to more than 20 antimicrobial agents and were resistant to ampicillin, selectrin, chloramphenicol, tetracycline, and streptomycin. However, JS33 differed from JS34 in hydrogen sulfide (H2S) generation. The genomic sequencing identified a deletion in thiosulfate reductase (K08352) in JS34.DiscussionH2S is an essential physiological regulator linked to inflammation and cancer. Therefore, genomic identification of JS33 and JS34 provided us with a better understanding of drug resistance and could be used as model strains to study the effects of microbial H2S production on the host. Since JS33 and JS34 did not induce gastrointestinal infection or other clinical symptoms as previously reported, the appearance of non-pathogenic S. Goldcoast in southeast China warned us to prepare for the prevalence of antimicrobial-resistant S. Goldcoast in China.
Morphosyntactic production and processing skills in relation to age effects and lexical-phonological levels among children with cochlear implants and typically hearing peers: a focus on vowel nasality
Authors: Fagniart Sophie , Charlier Brigitte , Delvaux Véronique , Harmegnies Bernard Georges , Huberlant Anne , Piccaluga Myriam , Huet Kathy 
Published: February 2025

IntroductionSignificant variability in the language performance of children with cochlear implant (CI) is widely recognized in the literature, particularly concerning morphosyntactic (MS) skills. The perceptual limitations of the CI, which can lead to phonological difficulties, may be responsible for this increased vulnerability in grammatical abilities. In this context, the present study focuses on the morphophonemic processing of items distinguished by nasal and oral vowels in the French language – the feature of vowel nasality being known as challenging for the CI population. Links between these performances with chronological/auditory ages and phonological and grammatical production skills will also be explored.MethodNineteen children with CIs and 47 children with typical hearing (TH) were assessed for phonological skills through a picture-naming task, perceptual skills through a task involving the sentence/word-picture matching task with word target containing nasal vs. oral vowels, and morphosyntactic production skills through narrative productions. Various measures of linguistic complexity [Mean Length of Utterance (MLU), verbs/utterances (V/U)] and lexical diversity (D index) were evaluated among our groups and linked to perceptual and productive phonological performances. Chronological and auditory ages as well as phonological accuracy and vocabulary levels as been studied as covariates.ResultsChildren with CIs displayed significantly lower morphosyntactic (MS) performance compared to peers with TH of the same chronological age, particularly in measures such as MLU in morphemes, complexity of function words, and processing of morphemes carried by nasal and oral vowels. However, when controlling for auditory age or phonological/lexical levels, these differences were no longer significant, suggesting a potential for compensation when similar auditory or linguistic experiences are achieved. Despite this, CI users showed distinct patterns of function word use, with fewer complex forms and more frequent errors, likely reflecting the perceptual challenges linked to CI. Additionally, a specific strong relationship between MS skills and phonological accuracy was observed in the CI group, potentially accounting for the marked inter-individual variability in MS development.ConclusionThe perceptual limitations of the CI have a significant impact on the linguistic development of children with CI and contribute to the widely documented variability in performance.
Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer’s disease
Authors: Alldred Melissa J. , Ibrahim Kyrillos W. , Pidikiti Harshitha , Lee Sang Han , Heguy Adriana , Chiosis Gabriela , Mufson Elliott J. , Stutzmann Grace E. , Ginsberg Stephen D. 
Published: February 2025

IntroductionIndividuals with Down syndrome (DS) exhibit neurological deficits throughout life including the development of in Alzheimer’s disease (AD) pathology and cognitive impairment. At the cellular level, dysregulation in neuronal gene expression is observed in postmortem human brain and mouse models of DS/AD. To date, RNA-sequencing (RNA-seq) analysis of hippocampal neuronal gene expression including the characterization of discrete circuit-based connectivity in DS remains a major knowledge gap. We postulate that spatially characterized hippocampal neurons display unique gene expression patterns due, in part, to dysfunction of the integrity of intrinsic circuitry.MethodsWe combined laser capture microdissection to microisolate individual neuron populations with single population RNA-seq analysis to determine gene expression analysis of CA1 and CA3 pyramidal neurons and dentate gyrus granule cells located in the hippocampus, a region critical for learning, memory, and synaptic activity.ResultsThe hippocampus exhibits age-dependent neurodegeneration beginning at ~6 months of age in the Ts65Dn mouse model of DS/AD. Each population of excitatory hippocampal neurons exhibited unique gene expression alterations in Ts65Dn mice. Bioinformatic inquiry revealed unique vulnerabilities and differences with mechanistic implications coinciding with onset of degeneration in this model of DS/AD.ConclusionsThese cell-type specific vulnerabilities may underlie degenerative endophenotypes suggesting precision medicine targeting of individual populations of neurons for rational therapeutic development.
Efficacy and safety of pharmacological and non-pharmacological therapies in Lennox-Gastaut syndrome: a systematic review and network meta-analysis
Authors: Zhu Zhengyan , Zhang Zhenpan , Xiao Wei , Wang Chunhua , Liang Risheng 
Published: February 2025

ObjectiveThis study aimed to evaluate the efficacy and safety of antiepileptic drugs and non-pharmacological treatments in patients with Lennox-Gastaut syndrome (LGS).MethodsWe conducted a systematic search of the PubMed, Embase, Cochrane, and Web of Science databases for randomized controlled trials (RCTs) evaluating both pharmacological and non-pharmacological interventions for LGS. The treatments assessed included cannabidiol, fenfluramine, clobazam, rufinamide, felbamate, lamotrigine, topiramate, deep brain stimulation, and anterior corpus callosotomy. The primary efficacy outcome was defined as a reduction of at least 50% in the frequency of drop seizures during treatment compared to baseline levels. The secondary efficacy outcome was measured as the median percentage reduction in monthly drop seizure frequency throughout the treatment period. Safety assessments were based on the incidence of adverse events and serious adverse events. All outcomes were ranked according to their surface under the cumulative ranking curve (SUCRA).ResultThis network meta-analysis encompassed 12 RCTs involving a total of 1,445 patients. The SUCRA indicated that clobazam 1 mg/kg/day, anterior corpus callosotomy, and rufinamide were the three most effective interventions for achieving a reduction of at least 50% in drop seizures. In terms of median percentage reduction in drop seizure frequency, clobazam 1 mg/kg/day ranked highest, followed by clobazam 0.5 mg/kg/day and rufinamide. Regarding safety profiles, SUCRA analysis revealed that cannabidiol 20 mg/kg/day had the highest likelihood of inducing adverse events, followed closely by fenfluramine 0.7 mg/kg/day. Lamotrigine was found to be most likely to cause serious adverse reactions, with cannabidiol 10 mg/kg/day following closely behind.ConclusionClobazam 1 mg/kg/day, anterior corpus callosotomy, and rufinamide manifested the most optimal efficacy in seizure control among LGS patients. Caution should be exercised when administering cannabidiol, lamotrigine, and fenfluramine 0.7 mg/kg/day in clinical practice to mitigate safety concerns associated with drug-related side effects.
Optimisation of cultivation conditions for Bacillus velezensis G7 from mangrove plants and exploration of potential bacteriocins
Authors: Li Yang , Ma Haotian , Pan Ruixue , Long Yuner , Zhao Yining , Yu Mengbo , Peng Jinju , Ma Yi 
Published: February 2025

IntroductionBacteriocin P7 was extracted from the cell-free supernatant (CFS) of Bacillus velezensis G7, which is a strain isolated from mangrove plants.MethodsIn this study, the culture conditions of B. velezensis G7 were optimised using an orthogonal test. The (CFS) was subsequently purified by using TA-GF75 gel chromatography, Tiderose Q HP anion chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC). Finally, the bacteriocin was identified by using LC-MS/MS.Results and discussionThe optimal culture conditions for B. velezensis G7 are 4.5 g/100 mL glucose, 1.5 g/100 mL yeast, and 1.2 g/100 mL MgSO4·7H2O. The stability of the CFS is affected by several factors, including heat, UV treatment and different storage conditions. High temperatures and long UV irradiation treatments significantly reduce the stability of CFS, which is more sensitive to strong acids, bases and enzymatic degradation. The minimum inhibitory concentration (MIC) of purified bacteriocin P7 against S. aureus was determined to be 30.352 μg/mL. On the basis of the results of the haemolytic activity assay, it was concluded that the use of bacteriocin P7 at concentrations equal to or below the 2 × MIC is safe. The addition of organic solvents and inorganic salts did not affect the bacteriocin P7, while the incorporation of SDS could enhance its antimicrobial efficacy. The bacteriocin was subjected to analysis by LC-MS/MS, which revealed that it was similar to the class I bacteriocin amyloliquecidin GF610. The findings of the present study indicate that the endophytic B. velezensis G7 from mangrove plant can produce bacteriocins, thereby providing a reference point for the expansion of novel bacteriocin sources.
Antiepileptic drugs and foetal disorders: analysis of 20-year data from the pharmacovigilance center
Authors: Ji Zejun , Nie Jianjun , Shen Qingli , Fu Zhonghua 
Published: February 2025

BackgroundFor women of childbearing age, the risks of uncontrolled epilepsy to the mother and fetus need to be balanced against the potential teratogenic effects of antiepileptic drugs (AEDs). The combined use of different types of AEDs has become a potential treatment option for the effective control of epileptic symptoms, while different studies present significant difference between the combined use of AEDs and foetal toxicity, which need a large comprehensive study to clarify the relation.ObjectiveThe study aims to analyze data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to explore the impact of monotherapy or polytherapy of AEDs on foetal and infant disorders.MethodsBayesian analysis and non-proportional methods were employed to assess the association between AED use and foetal disorders based on the FAERS database from the first quarter of 2004 to the fourth quarter of 2023. The clinical characteristics and outcome of patients were also investigated.ResultsThe study identified significant correlation between foetal disorders and the first and second generation AEDs, with RORs of 3.8 and 4.9, respectively. Valproic acid monotherapy showed the highest correlation with foetal disorders (ROR = 15.8, PRR = 16.3, IC025 = 3.8) and was uniquely associated with male reproductive toxicity. The risk of foetal disorders associated with combination therapies varied depending on the specific AEDs combination, with some increasing and others decreasing the risk compared to monotherapy.ConclusionThe analysis of the reports from FAERS database identified correlation between foetal disorders and AEDs and provided a comprehensive overview of the incidence and prognosis of different AEDs monotherapy and combination, which may provide some advice for the selection of drug for women of childbearing age.
Impact of straw return on greenhouse gas emissions from maize fields in China: meta-analysis
Authors: Sun Qi , Gu Xue-jia , Wang Yu-feng , Gao Hong-sheng , Wang Xiao-jun , Chen Xue-li , Sun Si-miao 
Published: February 2025

IntroductionAn increase in the amount of greenhouse gases (GHGs) in the atmosphere causes global warming, and &gt;14% of all GHG emissions come from agricultural activities. The three primary atmospheric GHGs are CO2, CH4, and N2O; therefore, regulating GHG emissions from agroecosystems is important for global climate management. Straw return is an environmentally friendly agricultural practice that positively affects crop production and soil fertility. However, its effects on long-term GHG emissions remain controversial.MethodsTo examine the impact of straw return on GHG emissions from Chinese maize fields, 281 data pairs from 45 publications were assessed using a data meta-analysis.ResultsThe findings demonstrated substantial increases in CO2 and N2O emissions of 140 and 40%, respectively. Methane emissions increased by 3% after straw return, and the maximum effect value of CO2 emissions was 2.66 at nitrogen rates&lt;150 kg/hm2. The effect value of CH4 emissions increased with an decrease in soil organic content, and the effect value of CH4 emissions changed from negative to positive at concentrations &gt;6 g/kg. With a nitrogen rate increase, N2O emission effects under straw return initially increased and then decreased. N2O emissions increased significantly when nitrogen rates were&lt;250 kg/hm2. The results of a random forest model showed that the most important factor affecting CO2 and N2O emissions from corn fields under straw return was the amount of nitrogen applied, and the most important factor affecting CH4 emissions from corn fields under straw return was soil organic carbon content.DiscussionThis shows that a suitable straw return can achieve the mutually beneficial goal of guaranteeing food security and minimizing adverse effects on the environment.