bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA-LNP vaccines combined with tPA signal sequence elicit strong protective immunity against
Klebsiella pneumoniae
Authors: Huang Ting , Che Siyou , Lv Zheng , Hao Danrui , Wang Runyu , Yi Qinxuan , Mei Ling , Yuan Yang , Zou Hang , Guo Yidong , Wang Xinrong , Chu Yiwen , Zhao Kelei 
Published: December 2024

ABSTRACT

Klebsiella pneumoniae
is a prominent Gram-negative and encapsulated opportunistic pathogen that causes a multitude of infections such as severe respiratory and healthcare-associated infections. Despite the widespread anti-microbial resistance and the high mortality rate, currently, no clinically vaccine is approved for battling
K. pneumoniae
. To date, messenger RNA (mRNA) vaccine is one of the most advancing technologies and are extensively investigated for viral infection, while infrequently applied for prevention of bacterial infections. In the present study, we aim to construct a new mRNA vaccine encoding YidR or combining with a tissue plasminogen activator signal sequence for preventing
K. pneumoniae
infection. Adaptive immunity was determined in mRNA vaccines-immunized mice and the protective effects of mRNA vaccines were evaluated in
K. pneumoniae
infected models. The results showed that lipid nanoparticle (LNP)-YidR-mRNA vaccine was produced with good morphology, high the encapsulation efficiency, and the specific antigen was highly expressed in cells
in vitro
. In addition, immunization with either LNP-YidR or LNP-YidR-SP elicited a Th1-biased immune response, reduced bacterial load, and provided broad protection in the lung infection models. Importantly, the LNP-YidR-SP mRNA vaccine induced strong adaptive humoral and cellular immunity and increased the survivability of mice compared to the other groups. Our findings serve as a focal point for developing a potential mRNA vaccine against
K. pneumoniae
, indicating the potential of mRNA vaccines for improving next-generation bacterial vaccine.

IMPORTANCE

K. pneumoniae
is a notorious and clinical bacterium that is evolving in community-acquired and nosocomial settings. This opportunistic pathogen causes severe infectious diseases, including urinary tract infection and pneumonia, and causes a concerning global public burden. Despite efforts having been created to develop different types of
K. pneumoniae
vaccines, there is no licensed vaccine for preventing
K. pneumoniae
infection. Therefore, to develop an effective tactic is essential to combat
K. pneumoniae
-caused diseases. This study provides a novel vaccine strategy against
K. pneumoniae
and a potent platform to elicit high levels of humoral and cell-meditated immunity.
Clinical and microbiological analyses of colistin-resistant strains among carbapenem-resistant
Enterobacter cloacae
complex clinical isolates
Authors: Yang Jinyoung , Baek Jin Yang , Ko Jae-Hoon , Huh Kyungmin , Cho Sun Young , Chung Doo Ryeon , Peck Kyong Ran , Huh Hee Jae , Ko Kwan Soo , Kang Cheol-In 
Published: December 2024

ABSTRACT

Carbapenem-resistant
Enterobacter cloacae
complex (CR-ECC), which is rapidly increasing as the cause of nosocomial infections, has limited treatment options. The aim of this study is to investigate the microbiological and clinical traits and molecular epidemiology of isolates of CR-ECC and provide guidance for antibiotic selection in clinical practice. Clinical CR-ECC isolates (ertapenem MIC ≥ 2 mg/L) were collected from 2021 to 2022. Species identification was performed using
hsp60
gene analysis, and antibiotic susceptibility tests were conducted by broth microdilution. The clinical characteristics of patients with CR-ECC isolates were retrospectively analyzed. Among the 108 CR-ECC isolates, 25 (23.2%) were non-susceptible to colistin, with colistin susceptibility being higher in
Enterobacter hormaechei
compared to non-
E
.
hormaechei
isolates (
P
< 0.0001). Of the 108 CR-ECC isolates, 9 (8.3%) produced carbapenemases, and only 6 of the 22 colistin-resistant CR-ECC isolates (27.3%) harbored the
mcr
gene. A total of 73 sequence types (STs), including 28 newly identified STs, were detected, demonstrating significant clonal diversity. The most common ST was ST74, known for its high prevalence and association with carbapenem resistance, with 77.8% identified as
E. hormaechei
subsp.
hoffmannii. E. hormaechei
was more common in the colistin-susceptible group than in the non-susceptible group (88.0% vs 37.5%,
P
< 0.0001), and
E. hormaechei
was the only protective factor for colistin resistance (HR 0.089, CI 0.030–0.261,
P
< 0.001). Although colistin resistance of CR-ECC is high, colistin could be administered safely to
E. hormaechei
. It is imperative to maintain ongoing surveillance and to further research on CR-ECC.

IMPORTANCE

Although new antibiotics are being developed, there are still limited options for treating carbapenem-resistant
Enterobacter cloacae
complex (CR-ECC) in regions where their use is restricted. The resistance level to one of these options, colistin, was investigated using bacteria isolated from clinical samples. In clinical practice, colistin is frequently administered empirically without susceptibility testing. However, this study suggests that colistin can be safely administered to certain species such as
Enterobacter hormaechei
within the CR-ECC.
How does gut microbiota affect the vaginitis axis? The mediating role of plasma metabolites
Authors: Li Mo , Zhang Qianyu , Wu Tong , Ma Lanfang , Hu Dianxing , Yuan Zixuan , Wang Shixuan , Luo Aiyue , Zhang Jinjin 
Published: December 2024

ABSTRACT

Vaginitis is the most common problem afflicting women of childbearing age. However, the underlying etiological factors remain poorly understood, leading to recurrent vaginitis and constraining clinical management. Here, we explored whether the gut microbiota influences the risk of vaginitis by performing a two-sample Mendelian randomization analysis using the largest genome-wide association studies to date. Four gut taxa in genus levels were identified related to vaginitis:
Candidatus Soleaferrea
(inverse-variance weighted [IVW] odds ratio [OR] = 2.20,
P
= 0.026),
Dialister
(IVW OR = 2.62,
P
= 0.029),
Lachnospiraceae UCG-008
(IVW OR = 0.41,
P
= 0.0067), and
Ruminiclostridium 5
(IVW OR = 0.080,
P
= 1.42 × 10
−5
). We further explored the mediation effect of the plasma metabolites by two-step Mendelian randomization (MR) and multivariable MR. The findings indicated that 3-phosphoglycerate and lysophosphatidylcholine antagonistically act against the two identified risk factors (
Candidatus Soleaferrea
and
Dialister
, respectively) of vaginitis, thus appearing to confer protective effects against vaginitis. On the contrary, the elevation of arachidonate/pyruvate ratio and reduction in palmitate/myristate ratio mediated the protective effects of
Lachnospiraceae UCG-008
against vaginitis. These findings support a potential causal role for gut microbiota in the development of vaginitis, thereby providing potential strategies for its prevention and intervention.

IMPORTANCE
Vaginitis is the most common problem afflicting women of childbearing age. However, the underlying etiological factors remain poorly understood, leading to recurrent vaginitis and constraining clinical management. Besides, the human gut and vagina are important organs that are both colonized by thousands of microorganisms impacting human physiology and health. Whether there is an interplay between the microecosystems is intriguing and unclear. This study evaluated the potential causal relationship between the gut microbiota and vaginitis and suggested that specific types of gut microbiota may be the potential risk or protective factors of vaginitis mediated or suppressed by certain plasma metabolites. These findings provide treatment insights for vaginitis.
Effects of head direction during prone position on postoperative delirium in elderly patients undergoing thoracolumbar spine surgery: a study protocol for a randomised controlled trial
Authors: Zhu Jixiang , Chen Yongzhuang , Chen Yangyang , Ma Hong , Liu Fengyun , Chen Qian , Wang Fang , Chen Xuetai , Xue Zhouya , Ni Kun , Li Feng , Qian Bin 
Published: December 2024

IntroductionProne positioning with head rotation can influence cerebral haemodynamics, potentially affecting cerebral perfusion and oxygenation. Elderly patients with impaired brain perfusion and oxygenation are at an increased risk of developing postoperative delirium (POD). Despite this, few studies have explored whether head orientation during prone positioning contributes to POD in older adults, an aspect often overlooked by clinicians. This study aimed to evaluate the impact of head orientation during prone positioning on the incidence of POD in elderly patients undergoing thoracolumbar spine surgery.Methods and analysisThis study is a single-centre, randomised, single-blind trial, with the assessors blinded to the intraoperative head position. Eligible participants are patients aged ≥65 years undergoing elective thoracolumbar spine surgery. A total of 500 patients will be randomly assigned to either the prone position with the head centred, or the prone position with the head deviated. The primary outcome is the incidence of POD, measured using the 3 min Diagnostic Interview for Confusion Assessment Method (3D-CAM) until postoperative day 5. Secondary outcomes include the severity of POD assessed by the Memorial Delirium Assessment Scale (MDAS), postoperative cognitive impairment evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), intraoperative regional cerebral oxygen saturation (rSO2), changes in vertebrobasilar artery and middle cerebral artery haemodynamics, and plasma levels of calcium channel-binding protein S100 subunit beta (S100B) and neuron-specific enolase (NSE).Ethics and disseminationEthical approval was obtained from Yancheng No. 1 People’s Hospital Ethics Examination Committee (2023-K-120–01). The findings will be disseminated through presentations at annual conferences and publications in scientific journals.Trial registration numberChiCTR2300078839.
Digital supportive supervision (DiSS) of maternal health, child health and nutrition (MCHN) service delivery in Rajasthan, India: study protocol for impact evaluation and cost-effectiveness analysis
Authors: Sharda Shweta , Kshtriya Pranav , Agrawal Praween Kumar , Singh Prakash , Trakroo Ajay , Joshi Anurag , Agarwal Anil , Goyal Aarti , D'Aquino Luigi , Singh Shubhra , Singh Raghuraj , Prinja Shankar 
Published: December 2024

BackgroundA digital supportive supervision (DiSS) tool was developed and implemented in Rajasthan, India, to enhance the coverage and quality of maternal health, child health and nutrition (MCHN) services. This study aims to assess the impact and cost-effectiveness of DiSS compared to traditional paper-based supportive supervision.Methods and analysisA quasi-experimental research design incorporating interrupted time series regression analysis will be employed to evaluate the impact of DiSS. Two districts from the high DiSS intensity group, defined as having at least 25% of the MCHN sessions supervised digitally, will be randomly selected as intervention districts. Two comparator districts will be selected from the low DiSS intensity group (less than 25% of MCHN sessions supervised digitally) after matching with intervention districts based on three indicators—female literacy, proportion of population belonging to scheduled caste or tribe and coverage of four antenatal care visits. District-level monthly data on the number of beneficiaries using MCHN services will be obtained from the state’s routine health management information system. Key informants involved in supervising MCHN sessions will also be interviewed to complement the quantitative findings. A mixed micro-costing methodology, incorporating top-down and bottom-up approaches, for assessing the cost of implementing supervision in either scenario. A decision model will estimate long-term health outcomes, in the form of quality-adjusted life years (QALY), in both the intervention and comparator groups. Cost-effectiveness of DiSS will be assessed by computing the incremental cost per QALY gained in the intervention versus comparator group.Ethics and disseminationThe study has been approved by the Institute Ethics Committee of the PGIMER, Chandigarh, India (IEC No. IEC-03/2023–2671). The study results will be disseminated at research conferences and published in peer-reviewed journals.
Pathway to care, treatment and disease burden of pulmonary arterial hypertension: a real-world survey of physicians and patients in Latin America
Authors: Orozco-Levi Mauricio , Souza Rogerio , Bluro Ignacio M , Harley Julia , Hernández Oropeza Jose Luis , Lescano Adrian , Meyer Gisela , Pineda Tatiana , Ramirez Alicia , Small Mark , Valencia Angelo , Pulido Tomás 
Published: December 2024

ObjectivesTo investigate clinical characteristics, symptom profile, testing practices, treatment patterns and quality of life (QoL) among patients with pulmonary arterial hypertension (PAH) in Latin America.DesignData from the Adelphi Real World PAH Disease Specific Programme, a cross-sectional survey with retrospective data collection.SettingUniversity/teaching hospital, regional centres, private practices and government institutions in Argentina, Brazil, Colombia and Mexico.Participants246 physicians provided data for 958 patients, of which 533 patients also self-reported data.ResultsMean (SD) patient age was 53.7 (17) years, 70% of patients were female and 79% were WHO functional class (WHO FC) I–II. Overall, 76% had undergone a right heart catheterisation, ranging from 92% in Argentina to 64% in Brazil (p<0.0001). Only 28% underwent a simplified risk assessment strategy in the past 12 months, ranging from 46% in Argentina to 16% in Brazil. Fatigue and dyspnoea on exertion were reported most commonly by physicians (37% and 53%) and patients (68% and 67%). Patient–physician agreement on symptom reporting was minimal-to-weak (kappa, 0.21–0.42). PAH-specific combination therapy varied across countries (21% Mexico, 30% Brazil, 70% Colombia and 79% Argentina, p<0.0001)). Overall, 73% of patients received a phosphodiesterase type 5 inhibitor; 52% an endothelin receptor antagonist, 15% a prostacyclin pathway agent and 11% a soluble guanylate cyclase stimulator. The mean (SD) EQ-5D (generic instrument to define quality of life)utility ranged from 0.66 (0.20) to 0.70 (0.20) across countries and the mean (SD) EQ-5D Visual Analogue Scale (VAS) was 67.0 (18.10). Lower VAS and utility scores were reported among patients with higher WHO FC (p<0.05).ConclusionsPatients reported a high burden of PAH in terms of symptoms and QoL, particularly within higher WHO FC. Low usage of risk assessment strategies and PAH-specific combination therapy was seen in Brazil and Mexico. Further research could identify barriers to prescribing optimal treatment.
Effects of intravascular administration of mesenchymal stromal cells derived from Wharton’s Jelly of the umbilical cord on systemic immunomodulation and neuroinflammation after traumatic brain injury (TRAUMACELL): study protocol for a multicentre randomised controlled trial
Authors: Sigaut Stéphanie , Tardivon Coralie , Jacquens Alice , Bottlaender Michel , Gervais Philippe , Habert Marie-Odile , Monsel Antoine , Roquilly Antoine , Boutonnet Mathieu , Galanaud Damien , Cras Audrey , Boucher-Pillet Hélène , Florence Aline-Marie , Cavalier Ines , Menasche Philippe , Degos Vincent , Couffignal Camille 
Published: December 2024

IntroductionTraumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Treatments for TBI patients are limited and none has been shown to provide prolonged and long-term neuroprotective or neurorestorative effects. A growing body of evidence suggests a link between TBI-induced neuro-inflammation and neurodegenerative post-traumatic disorders. Consequently, new therapies triggering immunomodulation and promoting neurological recovery are the subject of major research efforts. We hypothesise that repeated intravenous treatment with mesenchymal stromal cells derived from Wharton’s Jelly of the umbilical cord-derived mesenchymal stromal cells ((WJ-UC-MSC) may be associated with a significant decrease of post-TBI neuroinflammation and improvement of neurological status.Methods and analysisThe TRAUMACELL trial is a prospective, national multicentre, phase III, superiority, double-arm comparative randomised (1:1) double-blinded clinical trial. Among patients aged between 18–50, with a severe TBI defined by a Glasgow score less than 12 (within the first 48 hours) with brain traumatic lesion on CT Scan and needing intracranial pressure monitoring, with no other significant organ trauma (abbreviated injury scale<2) and unresponsive to verbal commands after 5 days of sedation discontinuation, 68 will be randomly allocated to receive either WJ-UC-MSC solution or placebo, with three intravenous injections 1 week apart. The primary outcome is the [18F]-DPA-714 signal intensity in corpus callosum measured by dynamic positron emission tomography (PET)-MRI at 6 months after the last injection, blinded to the randomisation arm, to evaluate the post-traumatic neuro-inflammation.Ethics and disseminationThe TRAUMACELL trial has been approved by an independent ethics committee (CPP SUD EST II) and French Medicines Agency (2023-504415-33-00) for all study centres. Participant recruitment will be starting in September 2024. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT06146062, first posted 24 November 2023Protocol version identifierTRAUMACELL−V.2.0_20240102
Management of uncomplicated acute appendicitis: a protocol for systematic review and network meta-analysis of randomised-controlled trials
Authors: Wang Xiaoyun , Liu Xueyu , Liu Yi , Long Lixi , Zhang Wei 
Published: December 2024

ObjectivesWhile multiple studies have shown the safety and efficacy of non-operative management, appendectomy remains the standard treatment for uncomplicated acute appendicitis (UAA). This study presents a protocol for a meta-analysis comparing antibiotic therapy, endoscopic retrograde appendicitis therapy (ERAT) and appendectomy in patients with UAA.Methods and analysisWe will conduct a systematic search of several databases, including PubMed, Web of Science, Embase, the China National Knowledge Infrastructure and the Cochrane Library. The search will cover the full range of database records up to September 2024. Eligible studies will include randomised-controlled trials (RCTs) evaluating the efficacy of antibiotic therapy, ERAT and appendectomy for UAA. The primary outcome will be treatment success, while secondary outcomes will include major complications, hospital costs, length of stay and recurrence of appendicitis. Two independent reviewers will select studies, extract data and assess bias risk. A Bayesian approach will be used for the network meta-analysis.Ethics and disseminationEthical approval is not required as the study will use data from published RCTs. The findings will be disseminated through publication in peer-reviewed journals.PROSPERO registration numberCRD42024554427.
Barriers to medication administration error reporting in a tertiary hospital in Lebanon
Authors: Mehanna Diala , El Gerges Najwa , Chalhoub Marianne , Daou Remy 
Published: December 2024

ObjectiveThe aim of this study is to identify the key barriers that prevent medication administration errors (MAEs) from being reported by nurses in Lebanese hospitals.MethodsA quantitative cross-sectional study was conducted at Hotel-Dieu de France Hospital using a self-administered questionnaire. A total of 275 responses were recorded and analysed using the IBM SPSS software V.23.0.ResultsOur study showed that ‘Fear’ and ‘Administrative response’ present the two main types of barriers to MAE reporting with a frequency of 62.9% and 60.7%, respectively, with more than half of our nurses confirming it (52.7%). The significant administrative barriers are: No positive feedback if medications were given correctly, too much emphasis being placed on MAE and the focus by the nursing administration on the individual rather than looking at the systems as a potential cause of the MAE whereas the significant fear barriers are the chances of suing the nurse if MAE is reported, the fear of adverse consequences of MAE reporting, the blame of nurses if something happens to the patient as a result of the MAE. No significant association was found between the barriers and demographic factors such as age, gender, experience and attending the training and orientation programmes.ConclusionThe findings highlight the need for targeted strategies to address these types of barriers. Anonymous error reporting, fostering a culture of transparency and adopting a non-punitive reporting system are approaches that can be implemented for optimal performance improvement, enhanced safety and healthcare quality and reduced wasting of the hospitals’ financial resources.
Novel pathways for headache via neurology same day emergency care: admission avoidance, prevention of lumbar punctures and reduced length of stay in hospital
Authors: Bierrum William , Spencer Jonathan Ian , Macarimban Roberto , Shirazi Ayala , Dethabrew Agampodi-Umanda , See Isaiah , Henry Alun Marc , Schlattl Anne , Alim-Marvasti Ali-Jesus , Balaratnam Michelle , Chandratheva Arvind , Baruah Tim , Simister Robert , Haider Salman 
Published: December 2024

There are various models for acute neurology services in the UK, with considerable variation in practice. Patients are often admittedunnecessarily for neurology review, leading to delay in diagnosis and treatment. Alternative models, such as the Neurology Same Day Emergency Care service (Neuro-SDEC) at University College London Hospital provide a pathway that can prevent admissions and streamline patient care. Headache is one of the commonest presenting symptoms in acute neurology.This study compared the impact of Neuro-SDEC on the care for patients presenting with headache against the standard pathway.A prospective audit was undertaken from November – December 2023 to evaluate all appropriate patients seen by the Neuro-SDEC service or admitted to the ward. For Neuro-SDEC patients, each case was reviewed to see whether an admission, lumbar puncture or neurology outpatient referral was avoided. For admitted patients, length of inpatient stay, time to neurology review and discharge diagnosis was recorded.Fifty-one patients were seen by Neuro-SDEC, twenty-five of whom would have been admitted to hospital on the standard pathway. Thirty general neurology outpatient clinic referrals were prevented and 5 patients avoided a lumbar puncture. In 45% of cases, the working diagnosis changed after the patient was seen by the Neuro-SDEC team. There were seven admitted patients not seen by the service with a combined length of stay of 17 bed days. The average wait time for inpatient neurology review was 42 hours. 3 admitted patients underwent a lumbar puncture. 2 patients were referred on to neuro-SDEC to enable an earlier discharge from hospital. Migraine was the most common final diagnosis in both groups.This study highlights that Neuro-SDEC is effective at reducing hospital admissions, as well as unnecessary tests and referrals to generalneurology outpatients. For admitted patients, the service enabled earlier discharge from hospital and reduced length of stay.