bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of bacterial quorum threshold for metabolic homeostasis and cooperativity
Authors: Goo Eunhye , Hwang Ingyu 
Published: December 2023

ABSTRACT

Many
Proteobacteria
employ an acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) system to control diverse social behaviors in a cell density-dependent manner. Various QS modulation mechanisms securing QS initiation at high cell density have been described. However, how QS bacteria determine the quorum threshold is less well known than expected, and little is known about how their physiological and social traits are affected by problems making such early decisions. Here, we show that the RNA-binding protein TofM binds to the mRNA of the QS signal synthase gene
tofI
and prevents QS signal biosynthesis at low cell density (LCD), thereby defining a stringent QS threshold for the rice pathogen
Burkholderia glumae
. The
tofM
mutant produced significant amounts of QS signals at LCD, resulting in a reduced growth rate due to advanced metabolic slowing and metabolic imbalance. When
tofM
mutants were grown in closed batch culture, mutants of
qsmR
, encoding a QS-dependent master regulator, spontaneously emerged. The same type of
qsmR
mutation was observed when low-density wild-type cells were cultured at AHL concentrations above the QS threshold. These data showed that translational control of the QS signal synthase gene at LCD is a stringent mechanism to maintain metabolic homeostasis and cooperativity in
B. glumae
. Our findings reveal that the bacterial genetic system has diversified to ensure the social activity of QS bacteria, as well as the possible consequences of QS bacteria at LCD encountering environments in which signals generated by their natural neighbors exceed their QS threshold.

IMPORTANCE
The mechanisms used by various bacteria to determine whether their density is sufficient to meet the QS threshold, how stringently bacterial cells block QS initiation until the QS threshold is reached, and the impacts of low-density bacterial cells encountering conditions that exceed the QS threshold are longstanding gaps in QS research. We demonstrated that translational control of the QS signaling biosynthetic gene creates a stringent QS threshold to maintain metabolic balance at low cell densities. The emergence of non-cooperative cells underlines the critical role of stringent QS modulation in maintaining the integrity of the bacterial QS system, demonstrating that a lack of such control can serve as a selection pressure. The fate of quorum-calling cells exposed to exceeding the QS threshold clarifies QS bacteria evolution in complex ecosystems.
A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study
Authors: Woolf Benjamin , Rajasundaram Skanda , Cronjé Héléne T , Yarmolinsky James , Burgess Stephen , Gill Dipender 
Published: December 2023

Abstract

Objective
To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.

Design
Two sample cis-mendelian randomisation study.

Setting
Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.

Participants
Individuals of European ancestry from the International Consortium for Blood Pressure (n=757 601) for estimating PDE5 inhibition (using the surrogate biomarker of diastolic blood pressure reduction), and UK Biobank (n=211 840) for estimating the fertility, sexual behaviour, and subjective wellbeing outcomes in male participants.

Intervention
Genetically proxied PDE5 inhibition.

Main outcome measures
Number of children fathered, number of sexual partners, probability of never having had sexual intercourse, and subjective wellbeing.

Results
Genetically proxied PDE5 inhibition was associated with male participants having 0.28 (95% confidence interval 0.16 to 0.39) more children (false discovery rate corrected P<0.001). This association was not identified in female participants. No evidence was found of an association between genetically proxied PDE5 inhibition and number of sexual partners, probability of never having had sexual intercourse, or self-reported wellbeing in male participants.

Conclusions
The findings of this study provide genetic support for PDE5 inhibition potentially increasing the number of children fathered by male individuals. Absence of this association in female participants supports increased propensity for sustained and robust penile erections as a potential underlying mechanism. Further studies are required to confirm this, however, and these findings should not promote indiscriminate use of PDE5 inhibitors, which can also have harmful adverse effects.
Role of artificial intelligence in imaging and endoscopy for the diagnosis, monitoring and prognostication of inflammatory bowel disease: a scoping review protocol
Authors: Chavannes Mallory , Kysh Lynn , Allocca Mariangela , Krugliak Cleveland Noa , Dolinger Michael Todd , Robbins Tom S , Rubin David T , Sagami Shintaro , Verstockt Bram , Novak Kerri 
Published: December 2023

IntroductionInflammatory bowel diseases (IBD) are immune-mediated conditions that are increasing in incidence and prevalence worldwide. Their assessment and monitoring are becoming increasingly important, though complex. The best disease control is achieved through tight monitoring of objective inflammatory parameters (such as serum and stool inflammatory markers), cross-sectional imaging and endoscopic assessment. Considering the complexity of the information obtained throughout a patient’s journey, artificial intelligence (AI) provides an ideal adjunct to existing tools to help diagnose, monitor and predict the course of disease of patients with IBD. Therefore, we propose a scoping review assessing AI’s role in diagnosis, monitoring and prognostication tools in patients with IBD. We aim to detect gaps in the literature and address them in future research endeavours.Methods and analysisWe will search electronic databases, including Medline, Embase, Cochrane CENTRAL, CINAHL Complete, Web of Science and IEEE Xplore. Two reviewers will independently screen the abstracts and titles first and then perform the full-text review. A third reviewer will resolve any conflict. We will include both observational studies and clinical trials. Study characteristics will be extracted using a data extraction form. The extracted data will be summarised in a tabular format, following the imaging modality theme and the study outcome assessed. The results will have an accompanying narrative review.Ethics and disseminationConsidering the nature of the project, ethical review by an institutional review board is not required. The data will be presented at academic conferences, and the final product will be published in a peer-reviewed journal.
Effect of intelligent hypertension management system on blood pressure: protocol for a randomised controlled multicentre trial
Authors: Yu Haiyang , Chen Xiang , Xia Jiachun , Hou Lei 
Published: December 2023

IntroductionHypertension is one of the most serious global health problems, and its prevention and treatment mainly rely on lifestyle intervention and medication. However, the current situation of hypertension control in China is still not ideal. Self-monitoring of blood pressure is expected to be a new way to control hypertension. Intervention and the Intelligent Hypertension Management System (IHMS), an information platform relying on the network and smartphone, may help patients self-monitor their blood pressure at home, allowing for intelligent management of hypertension. The aim of this trial is to investigate whether IHMS can effectively reduce blood pressure in patients with hypertension.Methods and analysisThis is a multiple-centre, prospective, randomised, controlled study. 320 eligible subjects will be randomly divided into the IHMS management group (n=160) and the conventional care group (n=160). Subjects in the IHMS management group will be required to take their blood pressure daily at regular intervals at home and get treatment as directed by the IHMS; the control group will receive conventional treatment. The primary outcome of the trial is the net change in systolic blood pressure at the end point of follow-up after 3 months. The mixed-effects model will be used to compare the primary outcome that there is a greater reduction in blood pressure in the intervention group than in the control group.Ethics and disseminationThe Ethics Committee of Shanghai Tongren Hospital has reviewed and approved the trial protocols, informed consent and subject information. The findings from the study will be disseminated through publications and conference presentations. The findings of the trial will be published in journals and presented at academic conferences.Trial registration numberNCT05526300.
Independent and joint associations of cardiorespiratory fitness and BMI with dementia risk: the Cooper Center Longitudinal Study
Authors: Gafni Tal , Weinstein Galit , Leonard David , Barlow Carolyn E , DeFina Laura F , Pettee Gabriel Kelley , Berry Jarett D , Shuval Kerem 
Published: December 2023

ObjectiveThis study aimed to examine the association of midlife fitness and body mass index (BMI) with incident dementia later in life.Design and participantsA cohort study of 6428 individuals (mean age 50.9±7.6 years) from the Cooper Center Longitudinal Study.MeasuresCardiorespiratory fitness and BMI were assessed twice (1970–1999) during visits to the Cooper Clinic, a preventive medicine clinic in Dallas, Texas. These measures were examined as continuous and categorical variables. As continuous variables, fitness and BMI were examined at baseline (averaged of two examinations) and as absolute change between exams (mean time 2.1±1.8 years). Variables were categorised: unfit versus fit and normal versus overweight/obese. Medicare claims data were used to obtain all-cause dementia incidence (1999–2009). Mean follow-up between midlife examinations and Medicare surveillance was 15.7 ((SD=6.2) years. Multivariable models were used to assess the associations between fitness, BMI and dementia.ResultsDuring 40 773 person years of Medicare surveillance, 632 cases of dementia were identified. After controlling for BMI and covariates, each 1-metabolic equivalent increment in fitness was associated with 5% lower (HR 0.95; 95% CI 0.90 to 0.99) dementia risk. In comparison, after controlling for fitness and covariates, each 1 kg/m2increment in BMI was associated with a 3.0% (HR 1.03; 95% CI 1.00 to 1.07) higher risk for dementia, yet without significance (p=0.051). Similar findings were observed when the exposures were categorised. Changes in fitness and BMI between examinations were not related to dementia. Jointly, participants who were unfit and overweight/obese had the highest (HR 2.28 95% CI 1.57 to 3.32) dementia risk compared with their fit and normal weight counterparts.ConclusionLower midlife fitness is a risk marker for dementia irrespective of weight status. Being unfit coupled with overweight/obese status might increase one’s risk for dementia even further.
Association of epicardial and visceral adipose tissue in relation to subclinical cardiac dysfunction in Chinese: Danyang study
Authors: Yao Fang , Zeng Lingkai , Hua Mulian , Zhang Siqi , Liang Junya , Gao Yun , Chen Chao , Zhao Xixuan , He Anxia , Liu Ming 
Published: December 2023

ObjectiveOur study aims to examine the associations of visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) with subclinical cardiac dysfunction in a Chinese population.DesignCross-sectional.BackgroundEAT and VAT are the most important ectopic fat pools which were previously shown to be associated with subclinical cardiac dysfunction. However, few studies simultaneously measured both EAT thickness and VAT area, and explored their associations with cardiac dysfunction. Our study aims to examine the associations of VAT and EAT with subclinical cardiac dysfunction in a Chinese population.MethodsThe study subjects were recruited from Danyang County from 2018 to 2019. Using Philips CX50, we recorded EAT thickness at the end-systole in a long-axis view. The subclinical systolic and diastolic function were assessed by two-dimensional speckle tracking, and transmitral and tissue Doppler imaging, respectively. Using Omron HDS-2000, we measured VAT area by dual bioelectrical impedance analysis.ResultsThe 1558 participants (age, 52.3±12.8 years) included 930 (59.7%) women. Compared with women, men had higher VAT area (99.4 vs 70.1 cm2; p<0.0001) but lower EAT thickness (4.02 vs 4.46 mm; p<0.0001). In simple correlation analyses, EAT thickness and VAT area were positively associated with E/e’ ratio (r=0.16 to 0.20; all p<0.0001) and negatively with global longitudinal strain (GLS) and e’ (r=−0.12 to −0.37; all p<0.0001). Furthermore, VAT area was associated with left ventricular ejection fraction (LVEF) (r=−0.14; p<0.0001). After adjustment for confounding factors, the association of EAT with GLS and that of VAT with e’ and E/e’ ratio remained significant (all p≤0.001), whereas the associations of EAT with subclinical diastolic dysfunction and that of VAT with systolic function became non-significant (all p≥0.11). Analyses on further adjustment for LVEF showed similar results.ConclusionsIncreased EAT thickness was associated with worse subclinical systolic dysfunction, while greater VAT area was associated with early diastolic dysfunction.
Neutrophil–lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis
Authors: Suzuki Yuzo , Kono Masato , Hasegawa Hirotsugu , Hashimoto Dai , Yokomura Koshi , Imokawa Shiro , Inoue Yusuke , Hozumi Hironao , Karayama Masato , Furuhashi Kazuki , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Suda Takafumi 
Published: December 2023

BackgroundIdiopathic pleuroparenchymal fibroelastosis (iPPFE), a progressive fibrotic disease, is characterised by upper lobe–dominant lung fibrosis involving the pleura and subpleural lung parenchyma. However, no prognostic markers have been established for this condition. Associations between blood leucocyte levels and mortality have been reported in patients with idiopathic pulmonary fibrosis; therefore, we hypothesised that peripheral leucocyte levels are associated with mortality risk in patients with iPPFE.MethodsThis retrospective study longitudinally assessed peripheral leucocyte counts at the time of diagnosis and 1 year after diagnosis in two cohorts of 127 patients with iPPFE (69 and 58 patients in Seirei and Hamamatsu cohorts, respectively).ResultsA comprehensive assessment of peripheral leucocytes revealed that the neutrophil–lymphocyte ratio (NLR) was associated with mortality in patients with iPPFE after adjusting for age, sex and forced vital capacity in multivariate analyses (adjusted HR, 1.131; 95% CI, 1.032 to 1.227). When the patients were classified based on the median NLR, those with a high NLR had shorter survival than those with a low NLR (median, 32.2 vs 79.8 months; HR, 2.270; 95% CI, 1.416 to 3.696). Interestingly, the results of the NLR classification by median were longitudinally preserved in >70% of patients, and patients with consistently high NLR were at a higher risk of mortality than others (median, 24.8 vs 79.6 months; HR, 3.079; 95% CI, 1.878 to 5.031). Compared with the gender–age–physiology model, a composite model comprising age, sex and NLR could successfully stratify patients with iPPFE into three groups according to mortality risk.ConclusionThe assessment of peripheral leucocyte counts is easy and might be useful in evaluating disease severity and mortality risk in patients with iPPFE. Our study suggests the importance of focusing on peripheral leucocyte levels in daily practice.
Interstitial lung disease following COVID-19 vaccination: a disproportionality analysis using the Global Scale Pharmacovigilance Database (VigiBase)
Authors: Lee Min-Taek , Lee Ju Won , Lee Hyeon Ji , Lee Jong-Min , Choi Jae Chol , Gu Kang-Mo , Jung Sun-Young 
Published: December 2023

Background and objectiveDespite several case reports, population-based studies on interstitial lung disease (ILD) following COVID-19 vaccination are lacking. Given the unprecedented safety issue of COVID-19 vaccination, it is important to assess the worldwide patterns of ILD following COVID-19 vaccination. This study aimed to investigate the signals of COVID-19 vaccine-associated ILD compared with other vaccinations using disproportionality analysis.MethodsWe analysed the VigiBase database during the period between 13 December 2020 and 26 January 2023. We adopted the case/non-case approach to assess the disproportionality signal of ILD for COVID-19 vaccines via 1:10 matching by age and sex. We compared COVID-19 vaccines with all other vaccines as the reference group.ResultsAmong 1 233 969 vaccine-related reports, 679 were reported for ILD. The majority of ILD cases were related to tozinameran (376 reports, 55.4%), Vaxzevria (129 reports, 19.0%) and elasomeran (78 reports, 11.5%). The reporting OR of ILD following COVID-19 vaccination was 0.86 (95% CI 0.64 to 1.15) compared with all other vaccines.ConclusionNo significant signal of disproportionate reporting of ILD was observed for COVID-19 vaccines compared with all other vaccines. Moreover, when compared with the influenza vaccines that are known to cause ILD, no signal was observed. This study results might help decision-making on the subsequent COVID-19 vaccination strategy of ILD. Further large and prospective studies are required for more conclusive evidence.
Use of a mini balloon microcatheter to facilitate penetration of fine vascular networks and curative embolization in vein of Galen malformations
Authors: Devarajan Alex , Schupper Alexander J , Rossitto Christina P , Bonet Jessica M , Sorscher Michelle , Vasan Vikram , Morgenstern Peter F , Ghatan Saadi , Shigematsu Tomoyoshi , Berenstein Alejandro , Fifi Johanna T 
Published: December 2023

BackgroundPatients with vein of Galen malformations (VOGMs) can develop fine angiogenic networks with fistulous connections to the precursor of the vein of Galen. In these cases, transarterial embolization (TAE) with liquid embolic agents (LEAs) is challenging due to reflux in the pedicle leading to the network, causing poor penetration. Transvenous approaches carry a risk of hemorrhage from pathologic vasculature. Dual-lumen balloon microcatheters like the Scepter Mini (Microvention, Aliso Viejo, CA) improve distal pedicle access, preventing reflux.ObjectiveHere, we report on the use of the Scepter Mini for TAE of angiogenic VOGM.MethodsA single-institution retrospective chart review identified all VOGMs treated with Scepter Mini microcatheters. Clinical data, angioarchitecture, and technical parameters were reviewed.Results17 Scepter Mini catheters were used in 12 embolization procedures of 7 patients with VOGM at a median age of 2.1 years. Patients presented with hydrocephalus (100%) and gross motor and speech delays (57.1%). Networks developed extra-axially into the subependymal zone fed by posterior choroidal, posterior cerebral, and thalamoperforator arteries. Posterior choroidal branches (n=7/17, 41.2%) were most frequently catheterized to achieve distal access to the network. Embolization with Onyx-18 and significant network penetration occurred in 17/17 uses. Near tip entrapment with LEA cast displacement occurred in 1/17 uses. Another patient experienced postprocedural intraventricular hemorrhage requiring a third ventriculostomy without permanent neurologic deficit.ConclusionThe Scepter Mini provided excellent distal access with penetration to the fistula and extra-axial network reduction with few complications. The Scepter Mini provides a means for successful treatment of technically challenging angiogenic VOGM.
Combined venous and arterial access in the arm for treatment of a complex dural arteriovenous fistula: a technical video
Authors: Silva Michael A , Abdelsalam Ahmed , Otvos Balint , Ramsay Ian , Fountain Hayes , Wu Eva , Starke Robert M 
Published: December 2023

Transvenous access is a necessary tool for numerous cerebrovascular pathologies.Transvenous access in the arm offers several benefits compared with transfemoral access, including patient comfort, the avoidance of transfemoral access complications, and the ability to close both radial arterial access and distal arm venous access with a single transradial compression band.1In this video we describe the indications, technical nuances, benefits, and limitations of transvenous access in the arm.Video 1- Combined venous and arterial access in the arm for treatment of a complex dural arteriovenous fistulaWe present the case of a young patient who presented with pulsatile tinnitus and was found to have a Cognard type IIa dural arteriovenous fistula near the left transverse sigmoid junction.The patient was treated with transvenous embolization via the distal right basilic vein, and a single radial compression band served to close both the arterial and venous access sites.
Prevalence of chronic non-cancer pain among military veterans: a systematic review and meta-analysis of observational studies
Authors: Qureshi Abdul Rehman , Patel M , Neumark S , Wang L , Couban R J , Sadeghirad B , Bengizi A , Busse J W 
Published: December 2023

IntroductionChronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs.MethodsFollowing Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence.ResultsForty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45–62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005).ConclusionWe found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain.