bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-184 targeting FOXO1 regulates host-cell oxidative stress induced by
Chlamydia psittaci
via the Wnt/β-catenin signaling pathway
Authors: Chen Lili , Huang Qiaoling , Luo Yuchen , Zhou You , Tong Ting , Chen Yuyu , Bai Qinqin , Lu Chunxue , Li Zhongyu 
Published: October 2023

ABSTRACT

Chlamydia psittaci
is a human pathogen that causes atypical pneumonia after zoonotic transmission. We confirmed that
C. psittaci
infection induces oxidative stress in human bronchial epithelial (HBEs) cells and explored how this is regulated through miR-184 and the Wnt/β-catenin signaling pathway. miR-184 mimic, miR-184 inhibitor, FOXO1 siRNA, or negative control sequence was transfected into HBE cells cultured in serum-free medium using Lipofectamine 2000. Then, prior to the cells were infected with
C. psittaci
6BC, and the cells were treated with or without 30 µM Wnt/β-catenin inhibitor ICG-001. Quantification of reactive oxygen species, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione was carried out according to the manufacturer’s protocol using a corresponding assay kit. The outcome of both protein and gene was measured by western blotting or real-time fluorescence quantitative PCR. In
C. psittaci
-infected HBE cells, miR-184 was upregulated, while one of its target genes,
FOXO1
, was downregulated. ROS and MDA levels increased, while SOD and GSH contents decreased after
C. psittaci
infection. When miR-184 expression was downregulated, the level of oxidative stress caused by
C. psittaci
infection was reduced, and the Wnt/β-catenin signaling pathway was inhibited. The opposite results were seen when miR-184 mimic was used. Transfecting with FOXO1 siRNA reversed the effect of miR-184 inhibitor. Moreover, when the Wnt/β-catenin-specific inhibitor ICG-001 was used, the level of oxidative stress induced by
C. psittaci
infection was significantly suppressed. miR-184 can target FOXO1 to promote oxidative stress in HBE cells following
C. psittaci
infection by activation of the Wnt/β-catenin signaling pathway.
Three small partner proteins facilitate the type VII-dependent secretion of an antibacterial nuclease
Authors: Yang Yaping , Boardman Eleanor , Deme Justin , Alcock Felicity , Lea Susan , Palmer Tracy 
Published: October 2023

ABSTRACT

The type VIIb secretion system (T7SSb) is a multisubunit protein export machine found in Gram-positive Bacillota which plays a key role in interbacterial competition. The T7SSb secretes a variety of toxic effector proteins targeting closely related strains; however, the mechanism of secretion and the roles of numerous conserved genes within T7SSb gene clusters remain unknown. EsaD is a nuclease toxin secreted by the
Staphylococcus aureus
T7SSb, which forms a pre-secretion complex with its cognate immunity protein, EsaG, and chaperone EsaE. Encoded upstream of EsaD are three small secreted proteins of unknown function: EsxB, EsxC, and EsxD. Here, we show that these three proteins bind to EsaD and function as EsaD export factors and we report preliminary structural information for a complete T7SSb substrate pre-secretion complex. Cryo-electron microscopy of the EsaDEG trimer and the EsaDEG-EsxBCD hexamer shows that incorporation of EsxBCD confers an elongated conformation comprising a flexible globular cargo domain attached to a long narrow shaft that is likely to be crucial for efficient toxin export.

IMPORTANCE

Staphylococcus aureus
is an opportunistic human pathogen associated with severe infections and antimicrobial resistance.
S. aureus
strains utilize a type VII secretion system to secrete toxins targeting competitor bacteria, likely facilitating colonization. EsaD is a nuclease toxin secreted by the type VII secretion system in many strains of
S. aureus
as well as other related bacterial species. Here, we identify three small proteins of previously unknown function as export factors, required for efficient secretion of EsaD. We show that these proteins bind to the transport domain of EsaD, forming a complex with a striking cane-like conformation.
Host cell sensing and restoration of mitochondrial function and metabolism within
Helicobacter pylori
VacA intoxicated cells
Authors: Seeger Ami Y. , Zaidi Faisal , Alhayek Sammy , Jones Rachel M. , Zohair Huzaifa , Holland Robin L. , Kim Ik-Jung , Blanke Steven R. 
Published: October 2023

ABSTRACT

Helicobacter pylori
vacuolating cytotoxin A (VacA) is an intracellular-acting protein exotoxin that induces mitochondrial dysfunction and energy depletion within host cells. Although exposure to VacA results in mitochondrial dysfunction, one recent study revealed that, following limited exposure to VacA, mitochondrial function and cellular ATP levels were restored in a time-dependent manner. Studies performed to address the mechanism by which host cells detect and respond to intracellular VacA identified the adenosine monophosphate (AMP)-activated protein kinase (AMPK) as a sensor of toxin-dependent alterations in cellular energy status. Activation of AMPK in response to VacA was demonstrated to orchestrate alterations in mitochondrial dynamics which resulted in restoration of mitochondrial function. Specifically, upregulation of dynamin-related protein 1 (Drp-1)-dependent mitochondrial fission resulted in reversible fragmentation of filamentous mitochondria and time-dependent reduction in mitochondrial-associated VacA, suggesting that fragmentation is important for removal of VacA from mitochondria. Cells with reduced levels of Drp-1 were more susceptible to VacA-dependent cell death, suggesting that mitochondrial dynamics is important for maintaining cell viability through the reduction in mitochondrial-associated toxin. Collectively, these studies support a model that cellular recovery and survival in response to VacA-dependent mitochondrial dysfunction is linked to host cell modulation of mitochondrial dynamics. This study provides new insights into cellular recognition and responses to intracellular-acting toxin modulation of host cell function, which could be relevant for the growing list of pathogenic microbes and viruses identified that target mitochondria as part of their virulence strategies.

IMPORTANCE

Persistent human gastric infection with
Helicobacter pylori
is the single most important risk factor for development of gastric malignancy, which is one of the leading causes of cancer-related deaths worldwide. An important virulence factor for
Hp
colonization and severity of gastric disease is the protein exotoxin VacA, which is secreted by the bacterium and modulates functional properties of gastric cells. VacA acts by damaging mitochondria, which impairs host cell metabolism through impairment of energy production. Here, we demonstrate that intoxicated cells have the capacity to detect VacA-mediated damage, and orchestrate the repair of mitochondrial function, thereby restoring cellular health and vitality. This study provides new insights into cellular recognition and responses to intracellular-acting toxin modulation of host cell function, which could be relevant for the growing list of pathogenic microbes and viruses identified that target mitochondria as part of their virulence strategies.
Inequalities in adequate maternal healthcare opportunities: evidence from Bangladesh Demographic and Health Survey 2017–2018
Authors: Methun Md Injamul Haq , Ahinkorah Bright Opoku , Roy Sutopa , Okyere Joshua , Hossain Md Ismail , Haq Iqramul , Ume Shatabdi Shamrita , Kamrul Hasan Md 
Published: October 2023

ObjectivesThis study investigated the inequalities in access to maternal healthcare services in Bangladesh.Design and settingThis study used cross-sectional data from the nationally representative Bangladesh Demographic and Health Survey conducted in 2017–2018. The survey encompassed diverse regions and households across Bangladesh. The study used the Human Opportunity Index (HOI) and Shapley’s decomposition technique to measure the inequality in access to maternal healthcare opportunities.ParticipantsThis study included 20 127 women aged 15–49 years. Among them, 5012 women had live births in the preceding 3 years of the survey, forming the study sample.Primary and secondary outcome measuresThis study has no secondary outcome variable. The primary dependent variable is ‘adequate maternal healthcare’, a dichotomous variable.ResultsHousehold wealth status contributed the highest to inequality in accessing adequate maternal healthcare services (41.4%) such as receiving at least four antenatal care (ANC) visits (39.7%), access to proper ANC (50.7% and 44.0%) and health facility birth (43.4%). Maternal educational status contributes the second highest inequality among all factors in accessing adequate maternal healthcare (29.5%). Adequate maternal healthcare presented the lowest coverage rate and opportunity index among all (approximately 24% with HOI=17.2).ConclusionsWe found that attained adequate maternal healthcare had the lowest coverage and widest dissimilarity, while wealth index, education and place of residence are the major factors that contribute to inequalities in accessibility to maternal healthcare services in Bangladesh. These findings underscore a need for pro-poor interventions to narrow the economic inequalities between the poor and rich in terms of accessibility to maternal healthcare services. The results indicate the need for the Bangladeshi government and its health department to strengthen their commitment to improving female education. Investments should be made in initiatives that facilitate the proximity of maternal healthcare services to women in rural areas.
Content development of the VISION-Cog: a novel tool to assess cognitive impairment in visually impaired older adults in Singapore
Authors: Vu Tai Anh , Fenwick Eva , Doshi Kinjal , Gupta Preeti , Quek Shin Yi , Chen Christopher , Ting Simon , Ng Adeline S L , Yap Philip , Yeo Donald , Milea Dan , Lamoureux Ecosse Luc 
Published: October 2023

ObjectivesCurrent cognitive screening and diagnostic instruments rely on visually dependent tasks and are, therefore, not suitable to assess cognitive impairment (CI) in visually impaired older adults. We describe the content development of the VISually Independent test battery Of NeuroCOGnition (VISION-Cog)–a new diagnostic tool to evaluate CI in visually impaired older Singaporean adults.DesignThe content development phase consisted of two iterative stages: a neuropsychological consultation and literature review (stage 1) and an expert-panel discussion (stage 2). In stage 1, we investigated currently available neuropsychological test batteries for CI to inform constructions of our preliminary test battery. We then deliberated this battery during a consensus meeting using the Modified Nominal Group technique (stage 2) to decide, via agreement of five experts, the content of a pilot neuropsychological battery for the visually impaired.SettingSingapore Eye Research Institute.ParticipantsStakeholders included researchers, psychologists, neurologists, neuro-ophthalmologists, geriatricians and psychiatrists.Outcome measurepilot VISION-Cog.ResultsThe two-stage process resulted in a pilot VISION-Cog consisting of nine vision-independent neuropsychological tests, including the modified spatial memory test, list learning, list recall and list recognition, adapted token test, semantic fluency, modified spatial analysis, verbal subtests of the frontal battery assessment, digit symbol, digit span forwards, and digit span backwards. These tests encompassed five cognitive domains–memory and learning, language, executive function, complex attention, and perceptual-motor abilities. The expert panel suggested improvements to the clarity of test instructions and culturally relevant test content. These suggestions were incorporated and iteratively pilot-tested by the study team until no further issues emerged.ConclusionsWe have developed a five-domain and nine-test VISION-Cog pilot instrument capable of replacing vision-dependent diagnostic batteries in aiding the clinician-based diagnosis of CI in visually impaired older adults. Subsequent phases will examine the VISION-Cog’s feasibility, comprehensibility and acceptability; and evaluate its diagnostic performance.
Diabetes care components effectively implemented in the ASEAN health systems: an umbrella review of systematic reviews
Authors: Te Vannarath , Ma Sokvy , Por Ir , Van Damme Wim , Wouters Edwin , van Olmen Josefien 
Published: October 2023

ObjectivesAssociation of Southeast Asian Nations (ASEAN) is among the hardest hit low-income and middle-income countries by diabetes. Innovative Care for Chronic Conditions (ICCC) framework has been adopted by the WHO for health system transformation towards better care for chronic conditions including diabetes. We conducted an umbrella review of systematic reviews on diabetes care components effectively implemented in the ASEAN health systems and map those effective care components into the ICCC framework.DesignAn umbrella review of systematic reviews and/or meta-analyses following JBI (Joanna Briggs Institute) guidelines.Data sourcesHealth System Evidence, Health Evidence, PubMed and Ovid MEDLINE.Eligibility criteriaWe included systematic reviews and/or meta-analyses which focused on management of type 2 diabetes, reported improvements in measured outcomes and had at least one ASEAN member state in the study setting.Data extraction and synthesisTwo reviewers independently extracted the data and mapped the included studies into the ICCC framework. A narrative synthesis method was used to summarise the findings. The included studies were assessed for methodological quality based on the JBI critical appraisal checklist for systematic reviews and research syntheses.Results479 records were found of which 36 studies were included for the analysis. A multidisciplinary healthcare team including pharmacists and nurses has been reported to effectively support patients in self-management of their conditions. This can be supported by effective use of digital health interventions. Community health workers either peers or lay people with necessary software (knowledge and skills) and hardware (medical equipment and supplies) can provide complementary care to that of the healthcare staff.ConclusionTo meet challenges of the increased burden of chronic conditions including diabetes, health policy-makers in the ASEAN member states can consider a paradigm shift in human resources for health towards the multidisciplinary, inclusive, collaborative and complementary team.
Multimodal prehabilitation to improve the clinical outcomes of frail elderly patients with gastric cancer: a study protocol for a multicentre randomised controlled trial (GISSG+2201)
Authors: Sun Yuqi , Tian Yulong , Cao Shougen , Li Leping , Yu Wenbin , Ding Yinlu , Wang Xixun , Kong Ying , Wang Xinjian , Wang Hao , Hui Xizeng , Qu Jianjun , Wang HongBo , Duan Quanhong , Yang Daogui , Zhang Huanhu , Zhou Shaofei , Liu Xiaodong , Li Zequn , Meng Cheng , Kehlet Henrik , Zhou Yanbing 
Published: October 2023

IntroductionGastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC.Methods and analysisThe study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients’ quality of life.Ethics and disseminationAll procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals.Trial registration numberNCT05352802.
Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China
Authors: Huang Lvdan , Cai Yaoyao , Yang Lili , Liu Le , Wang Quanguang , Shi Kejian 
Published: October 2023

ObjectiveThis study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery.DesignProspective single-centre randomised double-blind trial.SettingUniversity-affiliated hospital.ParticipantsSixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery.InterventionsBefore surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group.Primary and secondary outcome measuresThe primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness.ResultsCumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05).ConclusionUltrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery.Trial registration numberChinese Clinical Trial Registry (ChiCTR-IOR-17011960).
Efficacy of automated insulin delivery (AID) systems in type 1 diabetes: protocol of a systematic review and network meta-analysis of outpatient randomised controlled trials
Authors: Stahl-Pehe Anna , Schlesinger Sabrina , Kuss Oliver , Shokri-Mashhadi Nafiseh , Bächle Christina , Warz Klaus-D , Bürger-Büsing Jutta , Holl Reinhard , Spörkel Olaf , Rosenbauer Joachim 
Published: October 2023

IntroductionAutomated insulin delivery (AID), also known as artificial pancreas system or ‘closed-loop system’, represents a novel option for current treatments for type 1 diabetes (T1D). The objective of this systematic review and meta-analysis is to assess the efficacy of AID systems in comparison with current intensified insulin therapy for glycaemic control and patient-reported outcomes in individuals with T1D.Methods and analysisStudies will be eligible if they are randomised controlled trials (RCTs) in people with T1D of all ages, and if they compare an AID system for self-administration during the day and night period with any other type of insulin therapy for at least 3 weeks. The primary outcome will be time in the glucose target range of 70–180 mg/dL. A systematic review will be conducted in the MEDLINE, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov registries from their inception dates. Two authors will independently screen all references based on titles and abstracts against the eligibility criteria. For data extraction, standard forms will be developed and tested before extraction. All information will be assessed independently by at least two reviewers. The risk of bias of the included studies will be assessed using the Cochrane Risk of Bias 2 tool. The data synthesis will include a random-effects pairwise and network meta-analysis (NMA) in a frequentist framework. Where applicable and if sufficient RCTs are available, sensitivity analyses will be performed, and heterogeneity and publication bias will be assessed. The certainty of evidence from the NMA will be evaluated following the Grading of Recommendations Assessment, Development, and Evaluation working group guidance.Ethics and disseminationNo ethical approval is needed. The results will be reported to the funder, presented in a peer-reviewed scientific journal and at conferences, and disseminated via press release, social media and public events.PROSPERO registration numberCRD42023395492.