bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism for transmission and pathogenesis of carbapenem-resistant Enterobacterales harboring the carbapenemase IMP and clinical countermeasures
Authors: Yang Chengru , Jiang Shan , Wei Chunli , Li Chunjiang , Wang Jianmin , Li Xinhui , Zeng Lingyi , Hu Kewang , Yang Yang , Zhang Jisheng , Zhang Xiaoli 
Published: January 2024

ABSTRACT

Carbapenem-resistant Enterobacterales (CRE) are some of the most important pathogens causing infections, which can be challenging to treat. We identified four
bla
IMP
-carrying CRE isolates and collected clinical data. The transferability and stability of the plasmid were verified by conjugation, successive passaging, and plasmid elimination assays. The IncC
bla
IMP-4
-carrying pIMP4-ECL42 plasmid was successfully transferred into the recipient strain, and the high expression of
traD
may have facilitated the conjugation transfer of the plasmid. Interestingly, the plasmid showed strong stability in clinical isolates. Whole-genome sequencing was performed on all isolates. We assessed the sequence similarity of
bla
IMP
-harboring plasmid from our institution and compared it to plasmids for which sequence data are publicly available. We found that four
bla
IMP
-carrying CRE belonged to four different sequence types. The checkerboard technique and time-kill assays were used to investigate the best antimicrobial therapies for
bla
IMP
-carrying CRE. The time-kill assay showed that the imipenem of 1× minimum inhibitory concentration (MIC) alone had the bactericidal or bacteriostatic effect against IMP-producing strains at 4–12 h
in vitro
. Moreover, the combination of tigecycline (0.5/1/2 × MIC) and imipenem (0.5/1 × MIC) showed a bactericidal effect against the
bla
IMP-26
-carrying CRECL60 strain.

IMPORTANCE

Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat, and infections caused by these microorganisms are often associated with high mortality and limited treatment options. This study aimed to determine the clinical features, molecular characteristics, and plasmid transmissible mechanisms of
bla
IMP
carriage as well as to provide a potential treatment option. Here, we demonstrated that conjugated transfer of the IncC
bla
IMP-4
-carrying plasmid promotes plasmid stability, so inhibition of conjugated transfer and enhanced plasmid loss may be potential ways to suppress the persistence of this plasmid. The imipenem alone or tigecycline-imipenem combination showed a good bactericidal effect against IMP-producing strains. In particular, our study revealed that imipenem alone or tigecycline-imipenem combination may be a potential therapeutic option for patients who are infected with IMP-producing strains. Our study supports further trials of appropriate antibiotics to determine optimal treatment and emphasizes the importance of continued monitoring of IMP-producing strains in the future.
SARS-CoV-2 viral dynamics in a placebo-controlled phase 2 study of patients infected with the SARS-CoV-2 Omicron variant and treated with pomotrelvir
Authors: Borroto-Esoda Katyna , Wilfret David , Tong Xiao , Plummer Andrew , Kearney Brian , Kwong Ann D. 
Published: January 2024

ABSTRACT

Current guidelines recommend that individuals with moderate COVID-19 disease isolate for 5 days after the first appearance of symptoms or a positive SARS-CoV-2 test. It would be useful to understand the time course of infectious virus production and its correlation with virus detection using a rapid antigen test (RAT) or quantitative reverse transcriptase (qRT)-PCR. In a phase 2 study, 242 vaccinated patients with COVID-19 and at low risk for progression to severe disease initiated 5 days of treatment with pomotrelvir (PBI-0451, a SARS-CoV-2 main protease inhibitor) or placebo within 5 days after symptom onset. The primary endpoint, the proportion of subjects with SARS-CoV-2 viral titers below the limit of detection on Day 3 of treatment in the pomotrelvir versus placebo groups, was not met. No between-group differences in SARS-CoV-2 clearance or symptom resolution or alleviation were observed. Additional analyses evaluated the dynamics of SARS-CoV-2 replication in mid-turbinate nasal swabs and saliva samples using infectious virus assay (IVA), RAT, and qRT-PCR. SARS-CoV-2 cleared rapidly, with negative results first determined by IVA (TCID
50
below the limit of detection), followed by the RAT (negative for SARS-CoV-2 N antigen), and qRT-PCR (RNA below the limit of detection), which suggests that delayed initiation of treatment (up to 5 days after symptom onset) may have contributed to the lack of treatment response. Symptom resolution lagged behind viral clearance assessed by IVA and RAT. These data support reliance on a negative RAT to determine when an individual is no longer producing infectious virus and may end isolation.

IMPORTANCE
A phase 2 double-blind, placebo-controlled study was performed evaluating pomotrelvir, a SARS-CoV-2 Mpro inhibitor, compared with placebo in 242 non-hospitalized, vaccinated, symptomatic adults with COVID-19 (Omicron). No improvement in the decrease of viral replication or relief of symptoms was observed between the two groups when treatment was initiated ≥3 days after symptom onset. These results suggest that future COVID-19 antiviral studies using a similar patient population may need to initiate treatment earlier, like influenza studies. This is the first study to prospectively evaluate SARS-CoV-2 viral dynamics and the time to viral clearance in a significant number of patients using concurrently obtained results from an infectious virus assay, a rapid antigen test (RAT), and a qRT-PCR assay over a 15-day time course. These results suggest that a negative RAT assay is a good indicator of loss of infectious virus and the ability to return to normal activities.
Interspecific plant interaction structures the microbiomes of poplar-soil interface to alter nutrient cycling and utilization
Authors: You Yimin , Wang Liran , Liu Xiaoting , Wang Xuelai , Jiang Luping , Ding Changjun , Wang Weina , Zhang Dawei , Zhao Xiyang 
Published: January 2024

ABSTRACT

Terrestrial plants can influence the growth and health of adjacent plants through interspecific interaction. Here, the mechanisms of interspecific plant interaction on microbial function and nutrient utilization in the plant-soil interface (non-rhizosphere soil, rhizosphere soil, and root) were studied by soybean- and potato-poplar intercropping. First, metagenomics showed that soybean- and potato-poplar intercropping influenced the composition and co-occurrence networks of microbial communities in different ecological niches, with higher stability of the microbial community in soybean intercropping. Second, the gene abundance related to carbon metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling was increased at the poplar-soil interface in soybean intercropping. Moreover, soybean intercropping increased soil nutrient content and enzymatic activity. It showed higher metabolic potential in nutrient metabolism and transportation. Third, functional microorganisms that influenced nutrient cycling and transportation in different intercropping have been identified, namely
Acidobacteria
,
Sphingomonas
,
Gemmatimonadaceae
,
Alphaproteobacteria
, and
Bradyrhizobium
. Therefore, intercropping can construct microbial communities to alter metabolic functions and improve nutrient cycling and absorption. Interspecific plant interactions to influence the microbiome were revealed, opening up a new way for the precise regulation of plant microbiome.

IMPORTANCE
Poplar has the characteristics of wide distribution, strong adaptability, and fast growth, which is an ideal tree species for timber forest. In this study, metagenomics and elemental analysis were used to comprehensively reveal the effects of interspecific plant interactions on microbial communities and functions in different ecological niches. It can provide a theoretical basis for the development and application of the precise management model in poplar.
Double Mizoroki–Heck Arylation of Terminal Alkenes in the Presence of “Ligand-Free” Palladium Catalytic Systems
Authors: Kurokhtina A. A. , Larina E. V. , Lagoda N. A. , Grigoryeva T. A. , Schmidt A. F. 
Published: January 2024

Abstract
One-pot sequential double arylation of terminal alkenes with aryl halides to give trisubstituted derivatives is reported. The proposed approach is more advantageous than the known methods due to the use of a combination of low reactive but available aryl bromides or aryl chlorides and palladium-based “ligand-free” catalytic system.
Prevalence and early surgical outcome of congenital diaphragmatic hernia in the Netherlands: a population-based cohort study from the European Pediatric Surgical Audit
Authors: Teunissen Nadine Maria , Daniels Horst , Schnater J Marco , de Blaauw Ivo , Wijnen René M H 
Published: January 2024

BackgroundCongenital diaphragmatic hernia (CDH) is a rare birth defect with substantial mortality. This study aims to generate a population-based overview of CDH care and outcomes in the Netherlands. Moreover, it assesses interhospital variations between the two Dutch CDH expert centres.MethodsThis study uses data from the Dutch branch of the European Pediatric Surgical Audit, a prospective clinical audit for congenital anomalies. Data of all patients with CDH treated between 2014 and 2021 were included for epidemiological analysis. For comparative analyses, patients presenting after the neonatal period or not treated in the two CDH expert centres were excluded. Identified interhospital variations were assessed using regression analysis.ResultsIn the study period, 283 children with CDH were born, resulting in a national prevalence rate of 2.06/10 000 live births. The patient population, treatment and outcomes at 1 year were comparable between the hospitals, except for length of hospital stay. Regression analysis identified the treating hospital as the strongest significant predictor thereof. Other factors associated with longer length of stay include the presence of other malformations, intrathoracic liver position on prenatal ultrasound, extracorporeal membrane oxygenation treatment, patch repair, complicated postoperative course and discharge to home rather than to another care facility.ConclusionOutcomes of CDH care throughout the Netherlands are comparable. However, the length of stay differed between the two hospitals, also when adjusting for other covariates. Further qualitative analysis to explain this interhospital variation is indicated. Our findings underscore the potential of clinical auditing as a quality measurement tool in rare conditions.
Randomised controlled trial on the effect of social support on disease control, mental health and health-related quality of life in people with diabetes from Côte d’Ivoire: the SoDDiCo study protocol
Authors: Ekou Franck Kokora , Eze Ikenna C , Aka Joseph , Kwiatkowski Marek , Merten Sonja , Acka Felix Kouamé , Fink Günther , Utzinger Jürg , Probst-Hensch Nicole 
Published: January 2024

IntroductionDiabetes mellitus (DM) and its severe complications contribute significantly to disability and, hence, burden of disease. Poor mental health, a frequent DM consequence, may hinder successful diabetes control in low-income and middle-income countries (LMICs). Evidence suggests social support as a cost-effective tool to improve diabetes self-management, behaviour and mental health. However, its real-world application in LMICs has rarely been tested. We aim to investigate the effect of a social support intervention on disease control, mental health and health-related quality of life in people with diabetes from Côte d’Ivoire (SoDDiCo) through a randomised controlled trial.Methods and analysisThe trial will take place in the Centre Antidiabétique d’Abidjan, Institut National de Santé Publique, Abidjan, Côte d’Ivoire. We will prospectively randomise up to 1500 people with newly diagnosed diabetes into two parallel arms: intervention (routine care+family supporter accompanying clinical management) and control (routine care), using gender-stratified blocked randomisation with random block sizes of 10, 16, 20 and 24. Participants will undergo baseline, 3-month and 12-month postrandomisation assessments. The primary study outcome will be glycated haemoglobin (HbA1c). Secondary outcomes will include glycaemic control (HbA1c<7.0%), presence at follow-up visits, mental health and quality of life scores. Using intention-to-treat framework, we will assess the impact of the family support intervention on these endpoints over the course of the 1-year follow-up. Effect modification by baseline social capital will be assessed.Ethics and disseminationThe SoDDiCo trial was approved by the Ethikkommission Nordwest- und Zentralschweiz (ref: AO_2021-00041; approved: 12 July 2021) and by Comité National d'Éthique des Sciences de la Vie et de la Santé (ref: 049-22/MSHPCMU/CNESVS-kp; approved: 20 April 2022). The randomised intervention trial will follow good clinical practice guidelines. All results will be made available to the public through abstracts at conferences as well as through peer-reviewed articles. International guidelines for authorship will be respected.Trial registration numberISRCTN10901121, ISRCTN registry.
ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo
Authors: Schulz-Kuhnt Anja , Rühle Katharina , Javidmehr Asal , Döbrönti Michael , Biwank Jana , Knittel Selina , Neidlinger Peter , Leupold Jannik , Liu Li-Juan , Dedden Mark , Taudte Regina Verena , Gessner Arne , Fromm Martin F , Mielenz Dirk , Kreiss Lucas , Waldner Maximilian J , Schürmann Sebastian , Friedrich Oliver , Dietel Barbara , López-Posadas Rocío , Plattner Christina ,   The TRR241 IBDome Consortium, Zundler Sebastian , Becker Christoph , Atreya Raja , Neurath Markus F , Atreya Imke 
Published: January 2024

ObjectiveMucosal T cells play a major role in inflammatory bowel disease (IBD). However, their immunometabolism during intestinal inflammation is poorly understood. Due to its impact on cellular metabolism and proinflammatory immune cell function, we here focus on the enzyme ATP citrate lyase (ACLY) in mucosal T cell immunometabolism and its relevance for IBD.DesignACLY expression and its immunometabolic impact on colitogenic T cell function were analysed in mucosal T cells from patients with IBD and in two experimental colitis models.ResultsACLY was markedly expressed in colon tissue under steady-state conditions but was significantly downregulated in lamina propria mononuclear cells in experimental dextran sodium sulfate-induced colitis and in CD4+and to a lesser extent in CD8+T cells infiltrating the inflamed gut in patients with IBD. ACLY-deficient CD4+T cells showed an impaired capacity to induce intestinal inflammation in a transfer colitis model as compared with wild-type T cells. Assessment of T cell immunometabolism revealed that ACLY deficiency dampened the production of IBD-relevant cytokines and impaired glycolytic ATP production but enriched metabolites involved in the biosynthesis of phospholipids and phosphatidylcholine. Interestingly, the short-chain fatty acid butyrate was identified as a potent suppressor of ACLY expression in T cells, while IL-36α and resolvin E1 induced ACLY levels. In a translational approach, in vivo administration of the butyrate prodrug tributyrin downregulated mucosal infiltration of ACLYhighCD4+T cells and ameliorated chronic colitis.ConclusionACLY controls mucosal T cell immunometabolism and experimental colitis. Therapeutic modulation of ACLY expression in T cells emerges as a novel strategy to promote the resolution of intestinal inflammation.
Indian childhood cirrhosis: a retrospective study –redefining the older myths!
Authors: Goyal Surbhi , Singh Akanksha , Gangwar Shivanshu , Goyal Aditi , Sakhuja Puja , Kapoor Seema 
Published: January 2024

AimsThis retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management.MethodsThis study was done on liver archival tissue of our department from the period of January 2016 to December 2022. Of these, cases of copper overload on paediatric biopsies were retrieved. The histopathological features were scrutinised independently by three pathologists, correlating with their clinico-radiological investigations.ResultsFive children in infancy to middle childhood presented with features of chronic liver disease in the form of jaundice and abdominal distention, were included in the study. Characteristic ﬁrm hepatomegaly with sharp margins and transaminitis was noted in all cases. Autoimmune, viral and metabolic workup were negative in all these patients except one which showed positive autoimmunity and another whose Coomb’s test was positive. Normal ceruloplasmin levels and unremarkable slit lamp examination excluded the possibility of Wilson’s disease. The histological features of marked ballooning degeneration with diffuse Mallory Denk, pericellular fibrosis, absence of steatosis and panlobular copper deposits clinched the diagnosis of ICC.ConclusionsICC once believed to be extinct has still not vanished and remains underdiagnosed in routine practice. It is a rapidly fatal disease with a debatable pattern of inheritance and controversial role of copper as etiological agent. The clinical presentation is often deceptive and lack of awareness leads to misdiagnosis. Histopathological attributes are pathognomonic and possibility of ICC should be kept in all cases of cryptogenic cirrhosis.
Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients
Authors: Ali Rola H , Almanabri Mohamad , Ali Nawal Y , Alsaber Ahmad R , Khalifa Nisreen M , Hussein Rania , Alateeqi Mona , Mohammed Eiman M A , Jama Hiba , Almarzooq Ammar , Benobaid Noelle , Alqallaf Zainab , Ahmed Amir A , Bahzad Shakir , Almurshed Maryam 
Published: January 2024

AimsMitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait.MethodsWe retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations.ResultsOf 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2–17.6) and 21 adult patients (median 37 years; 18.9–89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs.ConclusionThe study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.
Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank
Authors: Casanova Francesco , Tian Qu , Atkins Janice L , Wood Andrew R , Williamson Daniel , Qian Yong , Zweibaum David , Ding Jun , Melzer David , Ferrucci Luigi , Pilling Luke C 
Published: January 2024

BackgroundBrain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter.MethodsWe analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia.ResultsIn Europeans, higher genetically predicted TSAT increased genetic liability to dementia (Odds Ratio [OR]: 1.15, 95% Confidence Intervals [CI] 1.04 to 1.26, p=0.0051), non-AD dementia (OR: 1.27, 95% CI 1.12 to 1.45, p=0.00018) and vascular dementia (OR: 1.37, 95% CI 1.12 to 1.69, p=0.0023), but not AD (OR: 1.00, 95% CI 0.86 to 1.15, p=0.97). Higher TSAT was also associated with increased risk of non-AD dementia in participants of African, but not South Asian groups. In survival analysis using a TSAT polygenic score, the effect was independent of apolipoprotein-E ε4 genotype (with adjustment subdistribution Hazard Ratio: 1.74, 95% CI 1.33 to 2.28, p=0.00006). Genetically predicted TSAT was associated with lower grey matter volume in caudate, putamen and thalamus, and not in other areas of interest.DiscussionGenetic evidence supports a causal relationship between higher TSAT and risk of clinically defined non-AD and vascular dementia, in European and African groups. This association appears to be independent of apolipoprotein-E ε4.
Nicotine beliefs and perceptions of low nicotine labels and mitigating statements among people who do and do not smoke: a cross-sectional study from Aotearoa New Zealand
Authors: Gendall Philip , Popova Lucy , Thrasher James , Hoek Janet 
Published: January 2024

BackgroundAotearoa New Zealand proposed a new maximum nicotine content of 0.8 mg/g for smoked tobacco products, although the new government plans to repeal this legislation. Requiring ‘Very low nicotine’ (VLN) messages on cigarettes meeting this standard may reinforce misperceptions that they are less harmful than cigarettes currently sold.MethodsTo explore knowledge of nicotine and very low nicotine cigarettes (VLNCs), and perceptions of cigarette packs featuring different low nicotine messages (eg, ‘Very low nicotine’) and mitigating statements (eg, ‘No cigarettes are safe’), we surveyed 354 people who smoked, 142 who formerly smoked, and 214 people who had never smoked regularly.ResultsAround half of all respondents believed VLNCs were less harmful than regular cigarettes and around two-thirds incorrectly thought nicotine causes most of the related health problems resulting from smoking. Nearly a third thought VLNCs would belessharmful than regular cigarettes; 34% believed they would be just as harmful. Mitigating statements did not affect perceptions of people who smoked, although people who formerly, or who had never smoked regularly, perceived mitigating statements referring to poisons and cancer as significantly more likely than the VLN message to discourage smoking.ConclusionsMisunderstanding of VLNCs as less harmful than regular cigarettes is widespread; VLN messages may reinforce this misperception, which mitigating statements did not correct among people who smoke. As an alternative to VLN messages, policy makers could consider introducing VLNCs on a specified date and developing public information campaigns; these measures would avoid phase-in confusion and obviate the need for VLN messaging.