bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination autologous stem cell transplantation with chimeric antigen receptor T-cell therapy for refractory/relapsed B-cell lymphoma: a single-arm clinical study
Authors: Li Danyang , Liu Rui , Fu Zhonghua , Yang Fan , Ma Lixia , Guo Yuelu , Cao Miaomiao , Lei Yang , Dou Yimeng , Zhang Xuenan , Gao Yan , Wei Bian , Deng Biping , Ke Xiaoyan , Hu Kai
Published: February 2025

Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cells (CAR-T) have been used as consolidation therapies for patients with refractory/relapsed B cell non-Hodgkin’s lymphoma (R/R B-NHL) in remission after second-line chemotherapy or salvage therapy. However, patients with different pathological subtypes and remission states may benefit differently from ASCT or CAR-T cell therapy. Furthermore, consolidation treatment involving ASCT or CAR-T cells still poses a significant risk of disease relapse. We conducted a retrospective, single-arm study of 47 patients with R/R B-NHL, and found that the combination of ASCT and CAR-T therapy improved the 3-year progression-free survival (PFS) and overall survival (OS) rates to 66.04% (95%CI: 48.311-78.928) and 72.442% (95%CI: 53.46-84.708) respectively. Furthermore, the combination therapy has no serious adverse events. Thus, ASCT combined with CAR-T cell therapy is effective against multiple subtypes of R/R B-NHL, and can effectively prolong the long-term survival of patients.
The clinical significance of T-cell regulation in hypertension treatment
Authors: Fu Miaoxin , Lv Mingzhu , Guo Jinyue , Mei Aihua , Qian Hang , Yang Handong , Wu Wenwen , Liu Zhixin , Zhong Jixin , Wei Ying , Min Xinwen , Wu Haiyan , Chen Jun
Published: February 2025

Hypertension, a globally prevalent condition, is closely associated with T cell-mediated inflammatory responses. Studies have shown that T cells, by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ), Interleukin-17 (IL-17), and Tumor necrosis factor-alpha (TNF-α), directly lead to vascular dysfunction and elevated blood pressure. The activation of Th1 and Th17 cell subsets, along with the dysfunction of regulatory T cells (Tregs), is a critical mechanism in the onset and progression of hypertension. This review explores the role of T cells in the pathophysiology of hypertension and discusses potential therapeutic strategies targeting T cell regulation, such as immunotherapy and gene-editing technologies. These emerging treatments hold promise for providing personalized therapeutic options for hypertensive patients, reducing inflammatory complications, and improving treatment outcomes.
Micro-encapsulated and colonic-release sodium butyrate modulates gut microbiota and improves abdominal pain in patients with symptomatic uncomplicated diverticular disease
Authors: Tursi Antonio , Procaccianti Giorgia , De Bastiani Rudi , Turroni Silvia , D’Amico Federica , Allegretta Leonardo , Antonino Natale , Baldi Elisabetta , Casamassima Carlo , Casella Giovanni , Ciuffi Mario , De Bastiani Marco , Lazzarotto Lorenzo , Licci Claudio , Mancuso Maurizio , Penna Antonio , Pranzo Giuseppe , Sanna Guido , Tosetti Cesare , Zamparella Maria , Picchio Marcello
Published: February 2025

The role of gut microbiota (GM) in the pathogenesis of Symptomatic Uncomplicated Diverticular Disease (SUDD) remains controversial. Here, we assessed the efficacy of a butyrate formulation in modulating GM and abdominal pain in patients with SUDD. A retrospective study was conducted in patients with SUDD who were treated with a delayed- and colonic-release formulation of butyrate (two capsules bid, for a total dose of 400 mg butyrate) for 3 months. GM was profiled before (T0) and after 90 days of treatment (T2) using 16S rRNA amplicon sequencing. The primary endpoint was change in GM at T2; secondary endpoints were reduction in abdominal pain severity according to VAS (Visual Analog Scale, 0: absence; 10: maximum severity) at T1 (45 days) and T2, stool characteristics according to the Bristol stool form scale at T0, T1 and T2, and safety of treatment. Fifty-nine patients with SUDD (59.3% male; median age 65.5 years, interquartile range 55–71 years) completed treatment. The butyrate formulation increased GM diversity and resulted in several compositional changes that were closely related to baseline abdominal pain severity. Regarding secondary endpoints, abdominal pain decreased significantly over time, while the Bristol stool form scale did not. Mild adverse events were recorded in 3 (5.08%) patients. This study showed that a microencapsulated and colonic-release formulation of butyrate favorably modulates GM and reduces abdominal pain in patients with SUDD.
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

Background

The 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.

Methods

In 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.

Results

Out 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.

Conclusion

The 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.
Upfront fixed-duration treatment strategies for chronic lymphocytic leukemia in Arab populations: a position statement from the Gulf region
Authors: Yassin Mohamed A. , Al Farsi Khalil , Hamad Anas , Ghasoub Rola , Alhuraiji Ahmad , Mheidly Kayane , Yaseen Hasan Aal , Osman Hani , Trepel Martin
Published: February 2025

The treatment landscape for chronic lymphocytic leukemia (CLL) has expanded dramatically over the last decade, with a wide range of effective treatments now available. Clinical management of CLL varies widely depending on patient profile, meaning the optimal treatment in Arab patients, who tend to be young and often present with comorbidities, including diabetes and obesity, requires specific considerations. In the absence of regional guidelines, a group of experts from across the Gulf region and one international expert from Germany convened to discuss and agree upon a position statement for venetoclax-based fixed-duration treatment strategies for Arab patients with CLL. Our position is that ibrutinib-venetoclax should be the first choice as first-line therapy for all fit CLL patients in the region, regardless of age. The advantages of an all-oral, fixed-duration treatment are discussed in the context of a young Arab patient population, including excellent patient and physician convenience, limited accumulative risk of toxicities, uncomplicated logistics, and low burden of healthcare administration costs. Finally, we discuss the management of key safety considerations in Arab populations including ethnic neutropenia, risk of cardiotoxic events, considerations during intermittent fasting, and avoiding adverse drug–drug interactions, e.g., with anti-tuberculosis or anti-obesity medications.
Superselective superior rectal artery embolization in the treatment of hemorrhoidal disease
Authors: Jiang Tao , Fan Lichao , Tang Xuesong , Xu Zhigang , Wu Wenjiang
Published: February 2025

Hemorrhoids are a prevalent and benign anal disorder for which minimally invasive treatments are increasingly preferred. The UK National Institute for Health and Care Excellence clinical guideline (2010) recommends hemorrhoidal artery ligation as a treatment option for hemorrhoidal disease. Superior rectal artery embolization (SRAE) leverages this principle by using digital subtraction angiography to precisely identify and superselectively embolize the arteries supplying the hemorrhoidal region. This procedure has demonstrated favorable clinical outcomes. SRAE is minimally invasive, painless, preserves the anal sphincter and normal anal anatomy, and offers a quick recovery, establishing it as an effective minimally invasive surgical option. As a result, this technique has gained increasing clinical recognition and adoption. This article examines the efficacy and safety of superselective SRAE for hemorrhoidal disease.
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

Background

MPT64 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.

Methods

DNA 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.

Results

Among 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 < 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%).

Conclusion

A 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

Introduction

Dairy 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.

Methods

Fecal 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.

Results

Among 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.

Discussion

This 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.
Bacteriophage P1 protein Icd inhibits bacterial division by targeting FtsZ
Authors: Zhao Kairui , Du Shuheng , Tian Linlin , Wang Shenping , Shi Runqin , Sun Haiyu , Zhou Yao , Huang Chenhao , Sun Yanmei , Wang Shiwei , Chen Yaodong
Published: February 2025

The study of bacteriophage (phage) gene products and their effects on the host helps to better understand the phage-host relationship and provides clues for the development of new antimicrobial proteins. In this study, we focused on a small protein named Icd with 73 amino acids from phage P1. It inhibits the growth of Escherichia coli and rapidly blocks the formation of Z-ring. The results of bacterial two-hybrid and pull-down experiments showed that Icd directly targets FtsZ, a key protein in bacterial division. Furthermore, we identified the core region of Icd as amino acids 12–51; this 40-amino acid protein had similar antibacterial activity to the full-length Icd, inhibiting bacterial growth and division.
Dynamic changes in the gut microbiota of SPF Bama piglets during breast and formula feeding
Authors: Zhang Chengcheng , Liu Zhengjiang , Yu Huan , Shen Yuanyuan , Lu Lu , Kong Fanli , Sun Wei , Wei Xiaoyuan , Jin Long , Ge Liangpeng , Zeng Bo
Published: February 2025

The gut microbiota plays a crucial role in the growth performance, health status, and welfare of pigs. Breast milk is a key factor in the colonization of gut microbiota and the overall health of newborn piglets. With advancements in breeding technology, formula milk has been widely adopted as a substitute for breast milk. This study aims to investigate the effects of sow feeding (natural breastfeeding) and formula milk feeding on the gut microbiota of specific pathogen-free (SPF) Bama pigs. Using metagenomic sequencing technology, we analyzed 114 fecal samples to uncover the impacts of different feeding methods on gut microbial diversity, dominant microbial populations, metabolic functions, carbohydrate-active enzymes (CAZymes), and antibiotic resistance genes (ARGs). The results revealed significant differences in the structure and function of gut microbiota between the breast milk (BM) group and the formula milk (FM) group at day 21. The BM group exhibited higher gut microbial diversity compared to the FM group, along with more extensive metabolic functions at both the gene and species levels. Notably, the FM group demonstrated higher activity in galactose metabolism and glycan metabolism, particularly at day 21. Additionally, the FM group showed significantly higher levels of ARGs against glycopeptide antibiotics at days 21 and 28 compared to the BM group. This study also found that breastfeeding and formula feeding differentially regulate the metabolic activity of gut microbiota and the expression of related enzymes, which may have long-term effects on nutrient absorption and disease resistance in pigs. These findings provide new insights into how different feeding methods shape the gut microbiota of pigs and offer a scientific basis for optimizing feeding strategies and improving breeding efficiency.
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

Introduction

Salmonella 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.

Methods

The 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.

Results

Two 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.

Discussion

H2S 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.
Effect of the CSFV NS5A protein on key proteins in the MAPK and PI3K-mTOR signaling pathways in porcine macrophages
Authors: Wang Yidan , Zheng Xiaoru , Yang Yingying , Zhao Xinru , Li Min , Huang Juan , Zhang Qiaoya , Qin Xiaobing , Yu Ying , Pan Qing , Cao Zhi
Published: February 2025

Classical swine fever (CSF) is a highly contagious disease caused by classical swine fever virus (CSFV). NS5A, a non-structural protein of CSFV, plays an important role in regulating viral replication and protein translation. The purpose of this study was to investigate the effects of the CSFV NS5A protein on key proteins in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) pathways in porcine macrophages. In this study, an NS5A lentivirus was constructed, and 3D4/21 cells were infected. The cells infected for 48 h were collected for proteomic analysis to screen the differential proteins in the two signaling pathways in the NS5A/control group, and the expression levels of key proteins were verified by Western blotting (Wb). CSFV NS5A lentivirus was successfully constructed and used to infect porcine macrophages, and 23 upregulated proteins and 16 downregulated proteins were found in the MAPK signaling pathway, whereas 5 upregulated and 15 downregulated proteins were found in the PI3K-mTOR signaling pathway. The results revealed that with increasing infection time, the expression of IKBKG, AKT1, CDC37, MAP3K2, and PKN2 decreased, whereas the expression of MAP3K7 and KRAS2 increased. The 3D4/21 cells infected with NS5A lentivirus and classical swine fever virus were inoculated, and the differential protein expression was verified via Wb. With increasing time, the protein expression levels of IKBKG and KRAS2 increased, whereas the protein expression levels of MAP3K7, MAP3K2, AKT1, CDC37, and PKN2 decreased. This study provides data for revealing the mechanism by which CSFV evades host antiviral immune clearance and has important scientific significance and potential application value.
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

Introduction

Significant 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.

Method

Nineteen 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.

Results

Children 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.

Conclusion

The 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.
How a patient-led advocacy organization supports the road to diagnosis and treatment of creatine transporter deficiency
Authors: Wallis Heidi , Iyer Sangeetha , Reinhardt Emily K.
Published: February 2025

The current era of drug development has evolved significantly. Patient advocacy organizations are moving beyond simply supporting community members and are taking the reins to improve the speed of diagnoses, initiate therapeutic discoveries, and lay the groundwork to ensure successful clinical trials. The Association for Creatine Deficiencies (ACD) is an international parent-led patient advocacy organization focused on the three ultra-rare neurodevelopmental monogenic disorders resulting in Cerebral Creatine Deficiency Syndromes (CCDS). These include X-linked creatine transporter deficiency (CTD), guanidinoacetate methyltransferase (GAMT) deficiency, and l-arginine:glycine amidinotransferase (AGAT) deficiency. While each is rare in its own right, the unified CCDS community is effectively advancing the field of CCDS with each disorder benefiting from progress made in the other two disease areas. ACD collaborators include caregivers, academic researchers, clinicians, industry partners, and policymakers. Since its founding in 2012, the organization has evolved and achieved significant milestones. These include advancements in disease diagnosis, investments in various therapeutic modalities, creation of a collaborative research community, a unified patient community contributing essential patient data, and repositories of patient-derived specimens. The initiatives of ACD are intended to create the earliest diagnosis possible through newborn screening, to have an effective treatment, and to make disease management strategies available to all members of the CCDS community, including those diagnosed at later stages and experiencing greater effects of the diseases.
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

Introduction

Individuals 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.

Methods

We 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.

Results

The 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.

Conclusions

These 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

Objective

This study aimed to evaluate the efficacy and safety of antiepileptic drugs and non-pharmacological treatments in patients with Lennox-Gastaut syndrome (LGS).

Methods

We 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).

Result

This 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.

Conclusion

Clobazam 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

Introduction

Bacteriocin P7 was extracted from the cell-free supernatant (CFS) of Bacillus velezensis G7, which is a strain isolated from mangrove plants.

Methods

In 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 discussion

The 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.
Small molecule inhibition of ubiquitin C-terminal hydrolase L1 alters cell metabolism proteins and exerts anti- or pro-tumorigenic effects contingent upon chemosensitivity status in high grade serous ovarian cancer
Authors: Jansen Corinne , McAdams Julia , Kim Chloe , De La Cruz Payton , Salaverria Angelica , DaSilva Nicholas A. , Grive Kathryn , James Nicole E.
Published: February 2025

High grade serous ovarian cancer (HGSOC) is the most lethal of all gynecologic malignancies in which the majority of patients eventually develop chemoresistant recurrent disease. Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme canonically known for its involvement in neurodegeneration, but recently has been shown to play a key role in tumorigenesis. Furthermore, UCHL1 has garnered attention across a multitude of cancer subtypes as it has the ability to be targeted through small molecule inhibition. Therefore, the goal of this present study was to elucidate mechanistic consequences of small molecule UCHL1 inhibition in HGSOC. Comparative label-free proteomic analysis of HGSOC cell line, OVCAR8 revealed prominent changes in cell metabolism proteins upon treatment with UCHL1 small molecule inhibitor, LDN-57444. Further validation via Western blot analysis revealed that changes in cell metabolism proteins differed in matched chemosensitive versus chemoresistant HGSOC cells. Finally, cell viability analysis demonstrated that a combinatorial carboplatin and LDN-57444 blockade produced a promotion or conversely, inhibition of cell death, in chemoresistant, and chemosensitve HGSOC cells, respectively. This phenomenon was further corroborated by respective differences in activation levels of common tumor cell growth pathways STAT3, MAPK/ERK, and AKT in chemoresistant versus chemosensitive HGSOC cells. Overall, this investigation established that pharmacologic targeting of UCHL1 produces differential effects according to HGSOC chemosensitivity status.
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

Background

For 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.

Objective

The 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.

Methods

Bayesian 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.

Results

The 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.

Conclusion

The 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

Introduction

An increase in the amount of greenhouse gases (GHGs) in the atmosphere causes global warming, and >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.

Methods

To 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.

Results

The 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<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 >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<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.

Discussion

This shows that a suitable straw return can achieve the mutually beneficial goal of guaranteeing food security and minimizing adverse effects on the environment.
The importance of moral fit to expectations of academic and professional wellbeing
Authors: Ongis Martino , Kidd David
Published: February 2025

What impact does moral fit have on expectations and engagement in higher education? We conducted two studies with college and university students in the U.S. In Study 1 (N = 151), we manipulated the moral fit of a hypothetical student, assessing its impact on anticipated academic, social, and professional outcomes. Study 2 (N = 201) involved manipulating moral values within a course description to investigate whether alignment with participants’ values influenced their interest in the course and expected outcomes. Both studies demonstrate that students are aware of moral fit in higher education, associating it with more positive expectations.
Linking air pollution appraisal to EFL teachers' negative emotion via mental effort: the moderating role of working memory capacity
Authors: Shi Yijun , Wang Shuhua , Hao Qi
Published: February 2025

Based on Cognitive Load Theory, this study developed a moderated mediation model to examine the relationship between English as foreign language (EFL) teachers' air pollution appraisal and negative emotions. Specifically, it hypothesizes that air pollution appraisal significantly increases the mental effort of EFL teachers, which in turn leads to the manifestation of negative emotions. Additionally, the study introduces the concept that the working memory capacity of EFL teachers can negatively moderate the impact of increased mental effort on their emotions, effectively attenuating the overall mediating effect. Data for this research was gathered from daily diary surveys of 182 EFL teachers across 23 high schools in Shanxi Province, China. The hypotheses were tested using two-level Hierarchical Linear Modeling and Monte Carlo analysis, with all proposed hypotheses receiving empirical support. This study significantly enriches the existing literature on air pollution appraisal, EFL teacher emotion, and Cognitive Load Theory, offering crucial practical insights for educational institutions on how to mitigate the adverse effects of air pollution on teachers.
The need for effective interprofessional collaboration between nutrition and dentistry
Authors: Kaye Jillian , Lee Sara , Chinn Courtney H.
Published: February 2025

There are bidirectional relationships between diet and nutrition, systemic health and oral health. Diet and nutrition are fundamental to the prevention and management of chronic diseases. Systemic health can impact oral health. And oral health can influence diet and nutrition. The 2020 Surgeon General’s Report “Oral Health in America” stated that nutrition is an integral factor in the development of oral disease and health overall. Within the medical model, Registered Dietitians have been impactful members of a multidisciplinary team by providing medical nutrition therapy and nutritional counseling to reduce the development and management of chronic diseases like obesity, diabetes and cardiovascular disease. Despite the well-established collaboration and the role nutrition plays in health outcomes, there is limited documented collaboration between nutrition and dentistry. The purpose of this paper is to review the current evidence of nutritional counseling in oral health settings compared to the medical model, identify specific challenges, and suggest possible next steps for collaboration. The intended outcome of this paper will be to provide the reader with insight about the need to integrate nutrition into both oral health education and clinical practice to address prevalent chronic diseases and increase health equity for those at high risk.
Artificial intelligence integration in surgery through hand and instrument tracking: a systematic literature review
Authors: Yangi Kivanc , On Thomas J. , Xu Yuan , Gholami Arianna S. , Hong Jinpyo , Reed Alexander G. , Puppalla Pravarakhya , Chen Jiuxu , Tangsrivimol Jonathan A. , Li Baoxin , Santello Marco , Lawton Michael T. , Preul Mark C.
Published: February 2025

Objective

This systematic literature review of the integration of artificial intelligence (AI) applications in surgical practice through hand and instrument tracking provides an overview of recent advancements and analyzes current literature on the intersection of surgery with AI. Distinct AI algorithms and specific applications in surgical practice are also examined.

Methods

An advanced search using medical subject heading terms was conducted in Medline (via PubMed), SCOPUS, and Embase databases for articles published in English. A strict selection process was performed, adhering to PRISMA guidelines.

Results

A total of 225 articles were retrieved. After screening, 77 met inclusion criteria and were included in the review. Use of AI algorithms in surgical practice was uncommon during 2013–2017 but has gained significant popularity since 2018. Deep learning algorithms (n = 62) are increasingly preferred over traditional machine learning algorithms (n = 15). These technologies are used in surgical fields such as general surgery (n = 19), neurosurgery (n = 10), and ophthalmology (n = 9). The most common functional sensors and systems used were prerecorded videos (n = 29), cameras (n = 21), and image datasets (n = 7). The most common applications included laparoscopic (n = 13), robotic-assisted (n = 13), basic (n = 12), and endoscopic (n = 8) surgical skills training, as well as surgical simulation training (n = 8).

Conclusion

AI technologies can be tailored to address distinct needs in surgical education and patient care. The use of AI in hand and instrument tracking improves surgical outcomes by optimizing surgical skills training. It is essential to acknowledge the current technical and social limitations of AI and work toward filling those gaps in future studies.
Pattern, severity, and treatment outcomes in acute poisoning patients admitted to the Saint Peter Specialized Hospital Toxicology Center in Addis Ababa, Ethiopia, 2023: a retrospective study
Authors: Kebede Yared Negussie , Mohammed Abdurehman Seid , Menberu Chekole Sileshi , Mekete Diress Getachew
Published: February 2025

Background

Poisoning is a global public health problem that has more unfavorable outcomes in developing countries. This study aimed to assess treatment outcomes and associated factors among poisoned patients treated at Saint Peter Specialized Hospital Toxicology Center.

Methods

An institutional-based retrospective cohort study was employed by reviewing medical chart records of acutely poisoned patients who had been admitted at St. Peter Specialized Hospital Toxicology Center on 01/01/2017 to 30/12/2023 and the medical chart records review was employed from 01/01/2024 to 30/01/2024. This study analyzed records of 553 poisoned patients. A systematic random sampling technique was used to select the study unit. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS) Windows version 26. A binary logistic regression model was used to identify associated factors for treatment outcomes of poisoned patients. A p-value <0.05 was considered statistically significant.

Result

A total of 553 documents of poisoned patients were assessed. The overall mortality rate was 18 (3.25%), and four patients developed chronic complications. Factor analyses show that arrival to the center before 4 h (AOR = 0.43, P = 0.008) predicted recovery, whereas arrival at the toxicology center after 8 h (AOR = 2.21, P = 0.004), being hypotensive (AOR = 1.85, P = 0.002), needing intubation (AOR = 2.52, P = 0.014), and the presence of two or more complication (AOR = 3.3, P < 0.001) at admission were predictors of mortality.

Conclusion and Recommendation

The mortality rate for poisoned patients was 18 (3.25%). In this study, delayed arrival to the toxicology center, being hypotensive, needing intubation, and the presence of two or more complications at admission were factors associated with the mortality and morbidity of the patients. Establishing a strong referral link between the toxicology center and regional health institutions, ensuring the availability of possible advanced clinical setup early recognition, and aggressively resuscitating critically ill patients will help minimize unfavorable outcomes.