bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tebipenem pivoxil as an alternative to ceftriaxone for clinically non-responding children with shigellosis: a randomised non-inferiority trial protocol
Authors: Nuzhat Sharika , Islam Md Ridwan , Das Subhasish , Bashar Syed Jayedul , Pavlinac Patricia B , Arnold Samuel L , Newlands Amy , Gibson Rachel , Alvaro Elena Fernandez , Addo Juliet , Khanam Farhana , Ahmed Dilruba , Chisti Md Jobayer , Qadri Firdausi , Ahmed Tahmeed 
Published: February 2025

Introduction
Shigellosis is the second leading cause of diarrhoeal deaths among children worldwide. Oral azithromycin and intravenous ceftriaxone are the recommended first-line and second-line therapies for shigellosis in Bangladesh, respectively, but growing antibiotic resistance will require new antibiotic options. Tebipenem pivoxil, an orally administered carbapenem antibiotic with activity against many strains of antibiotic-resistant bacteria, may be a viable option.

Methods

A phase IIb randomised controlled trial was planned to determine the efficacy and safety of oral tebipenem pivoxil, compared with intravenous ceftriaxone, for children with
Shigella
diarrhoea unresponsive to the first-line antibiotic therapy. We will enrol 132 children in the trial (66 in each arm). Children from Bangladesh aged 24–59 months suspected of having
Shigella
diarrhoea, with no clinical improvement within 48 hours of starting first-line therapy, will be randomised to a 3-day course of intravenous ceftriaxone (50 mg/kg, once a day) or a 3-day course of oral tebipenem pivoxil (4 mg/kg, three times a day). The children will be evaluated for key clinical, microbiological and safety outcomes during the subsequent 30-day period. Clinically, failure at day 3 will be defined as the presence of fever (axillary temperature ≥38°C), diarrhoea (three or more abnormally loose or watery stools in the last 24 hours), blood in stool, or abdominal pain/tenderness at day 3 of follow-up or death or hospitalisation prior to day 3. It is hypothesised that children treated with tebipenem pivoxil will have no worse clinical and microbiological failure rates compared with ceftriaxone.

Ethics and dissemination
This study protocol was approved by the institutional review board of the International Centre for Diarrhoeal Disease Research, Bangladesh, which comprises a research review committee and an ethics review committee. In addition, the use of tebipenem pivoxil in shigellosis was approved by the Directorate General of Drug Administration of Bangladesh.

Trial registration number

NCT05121974
.
Efficacy of synovectomy in the treatment of femoral head osteonecrosis with vascularised fibular grafting in Shanghai: a protocol for SYNERGY-VGF trial
Authors: Fu Kai , Zheng Wei , Cai Qianying , Peng Hao , He Haiyan , Zhu Daoyu , Jiang Chenyi , Wang Zehao , Ding Peng , Yin Jimin , Jin Dongxu , Zhang Changqing , Gao Youshui 
Published: February 2025

BackgroundOsteonecrosis of the femoral head (ONFH) is characterised by progressive bone death, leading to joint incongruity and eventual osteoarthritis. Various interventions have been explored to forestall disease progression and delay total hip arthroplasty (THA). Free vascularised fibula grafting (FVFG) has shown promise, particularly in the precollapse stages of ONFH. However, the potential benefits of combining synovectomy with FVFG to address synovitis in ONFH have not been systematically studied. This trial seeks to compare outcomes between patients undergoing FVFG with and without synovectomy.Methods and analysisThe trial is a randomised, single-centre, parallel-group trial comparing FVFG with synovectomy versus FVFG alone in patients with ONFH and synovitis. 90 participants will be randomised into two groups: synovectomy (n=45) and non-synovectomy (n=45). The primary outcome is the Harris Hip Score (HHS) change at 12 months post surgery. Secondary outcomes include HHS, Numeric Rating Scale (NRS) for pain, Depression Anxiety Stress Scales-21 (DASS-21), and EQ-5D scale assessments at intervals up to 12 months post randomisation.Ethics and disseminationThis trial was approved by the Human Research Ethics Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine prior to patient recruitment (approval number: 2023-076). Results from this trial will be published in peer-reviewed journals. Results will also be presented at international conferences.Trial registration numberChinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2300073385. Prospectively registered on 10 July 2023.
Role of the collagen scaffold in preventing intrauterine adhesion from recurrence after adhesiolysis: protocol for a multicentre, randomised, controlled, parallel-group, open-label, superiority clinical trial
Authors: Li Taishun , Wang Huiyan , Xu Biyun , Zhu Hui , Hu Yali 
Published: February 2025

IntroductionIntrauterine adhesions (IUAs) are one of the most common causes of uterine infertility. Hysteroscopic adhesiolysis is the primary treatment for IUA, but the rate of IUA recurrence is high in moderate to severe cases. While traditional guidelines recommend placing a non-copper stainless steel intrauterine device (IUD) into the uterine cavity after adhesiolysis to prevent readhesion, the preventive effect is uncertain. Our preliminary trials suggested that the collagen scaffold was more effective in moderate cases. This study aims to assess the efficacy and safety of a collagen scaffold versus IUD in preventing readhesion after hysteroscopic adhesiolysis in patients with moderate IUA.Methods and analysisThis multicentre, open-label, randomised controlled trial evaluates the efficacy and safety of a collagen scaffold compared with an IUD in preventing readhesion after hysteroscopic adhesiolysis in women with moderate IUA. This trial will be conducted at six teaching hospitals and plans to enrol 200 participants. The primary outcome is the non-recurrence rate of IUA 2 months after adhesiolysis. Secondary endpoints include changes in American Fertility Society scores before and after surgery and postoperative menstrual blood volume. The 95% CIs for the difference in non-recurrence rates between the two groups will be calculated. If the lower limit of this interval exceeds the superiority threshold of zero, the conclusion of superiority is confirmed.Ethics and disseminationThis study has received approval from the ethics committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School (2022-491-02) and the ethics committees of the participating centres. Written informed consent will be obtained from each participant before starting any study procedures. The results of this trial will be published in a peer-reviewed journal.Trial registration numberChiCTR2300068271.
Comparison of remimazolam-based and propofol-based general anaesthesia on postoperative quality of recovery in patients undergoing laparoscopic sleeve gastrectomy: protocol for a prospective, randomised, parallel-group, non-inferiority trial
Authors: An Dong-jiao , Wang Jing , Ren Chuning , Zhao Yanjun , Wei Changwei , Wu Anshi 
Published: February 2025

IntroductionRemimazolam is a novel short-acting benzodiazepine that exhibits sedative and hypnotic properties without compromising respiratory function and while maintaining haemodynamic stability. Its safety and efficacy have been demonstrated to be non-inferior to those of propofol in the context of general anaesthesia. Nevertheless, the non-inferiority in terms of postoperative recovery quality in obese patients has not been established. Thus, we conducted a prospective, randomised, parallel-group, non-inferiority study to compare remimazolam-based general anaesthesia with propofol-based general anaesthesia on the postoperative quality of recovery (QoR) in patients undergoing laparoscopic sleeve gastrectomy.Methods and analysisAll participants meeting the included criteria will be enrolled after signing an informed consent form. Patients will be randomly allocated to either the propofol group (n=63; induction and maintenance with propofol) or the remimazolam group (n=63; induction and maintenance with remimazolam). The primary endpoint of the study is the 15-item QoR Scale assessed at 24 hours postoperatively. Secondary endpoints include the doses of anaesthetic required for loss of consciousness (LOC), the time to LOC, the time to recovery of consciousness, the total amount of anaesthetic administered during the surgery and the incidence of hypotension and bradycardia. Additionally, postoperative profiles of pain, nausea and vomiting, delirium, intraoperative awareness, adverse events and patient satisfaction will be collected. Statistical analyses will be performed using IBM SPSS Statistics V.26.0 and GraphPad Prism V.5.01. Statistical significance is set at two-sided p values<0.05.Ethics and disseminationEthical approval was obtained from the ethics committees of Beijing Chaoyang Hospital, Capital Medical University (No. 2023ke715-1). The findings will be disseminated in peer-reviewed publications.Trial registration numberChiCTR2400083700.
What are the lived experiences of patients with cancer and their families in northern Ghana? A qualitative study using narrative interview and creative task approach
Authors: Tuck Chloe Zabrina , Akparibo Robert , Gray Laura A , Suraj Hamza , Iddrisu Abdul-Rashid Timtoni , Abane Tampuri Rahman , Deedat Alhassan Ahmed , Aryeetey Richmond Nii Okai , Abubakari Braimah Baba , Azure Amos , Cooper Richard 
Published: February 2025

ObjectivesCancer poses a major burden in Ghana that is exacerbated by poor engagement with biomedical treatment. The reasons for this are not well understood for most cancers and in northern Ghana.DesignThis research took combined narrative interviews with a creative task that was analysed through reflexive thematic analysis.SettingA tertiary treatment centre in northern Ghana.Participants15 adult (>18 years) patients or their relatives who had been diagnosed and/or treated for cancer within the last 2 years.ResultsThe thematic analysis highlighted the psychological burden of cancer and ways participants cope and find meaning, including through religion, trust in biomedical treatment, and occupation and social support. The findings stress the negative impact of the financial burden, shame, worry and the spiralling poverty this causes.The creative task was found to be resonant, emotive and more humanising, which is anticipated to be more effective when communicating with policy-makers and community members. The findings provide rich contextual insights to understand patients’ and relatives’ perspectives and frame their experiences within what was important to them.ConclusionsTogether the research has identified a critical need for policy to consider the psychosocial, occupational, spiritual and financial needs of patients with cancer in northern Ghana. It has demonstrated narrative interviews with graphical elicitation as an effective approach to discuss sensitive topics for findings that can engage stakeholders and inform holistic cancer service design.
Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis
Authors: Trebicka Jonel , Aguilar Ferran , Queiroz Farias Alberto , Lozano Juan-José , Sánchez-Garrido Cristina , Usón-Raposo Eva , de la Peña-Ramirez Carlos , Sidorova Julia , Curto-Vilalta Anna , Sierra-Casas Patricia , Momoyo Zitelli Patricia , Papp Maria , Pereira Gustavo , Caraceni Paolo , Goncalves Luciana L , Alessandria Carlo , Torre Aldo , Laleman Wim , Gadano Adrián , Piano Salvatore , Mattos Angelo Z , Gu Wenyi , Brol Maximilian Joseph , Schierwagen Robert , Uschner Frank Erhard , Fischer Julia , Mendes Liliana S C , Vargas Victor , Alvares-da-Silva Mario R , Mookerjee Raj , Bittencourt Paolo L , Benitez Carlos , Albillos Agustín , Couto Cláudia , Mendizabal Manuel , Bañares Rafael , Toledo Claudio L , Mazo Daniel F , Janicko Martin , Castillo-Barradas Mauricio , Padilla Machaca Pedro Martin , Gatti Pietro , Miranda Adelina Zarela-Lozano , Malé-Velázquez René , Zipprich Alexander , Castro-Lyra André , Gustot Thierry , Bernal William , Gerbes Alexander L , Jalan Rajiv , Fernández Javier , Angeli Paolo , Carrilho Flair Jose , Claria Joan , Moreau Richard , Arroyo Vicente 
Published: February 2025

Background and aimsQuantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.MethodsStandard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients.ResultsThe CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission.ConclusionsIn patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.
Serological screening for coeliac disease in an adult general population: the HUNT study
Authors: Andersen Ina Lervåg , Lukina Polina , Dyrli Ole T , Klaasen Rolf Anton , Warren David John , Bolstad Nils , Mjønes Patricia , Rønne Elin , Iversen Rasmus , Sollid Ludvig M , Lundin Knut E A , Ness-Jensen Eivind 
Published: February 2025

BackgroundA large proportion of individuals with coeliac disease (CeD) remain undiagnosed.ObjectiveThe aim of this study was to assess serological screening for CeD in the adult general population.DesignThe study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found.ResultsHistological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals.ConclusionThe TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.
Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium
Authors: Tseng Ching-Hung , Wong Sunny , Yu Jun , Lee Yeong Yeh , Terauchi Jun , Lai Hsin-Chih , Luo Jiing-Chyuan , Kao Cheng Yen , Yu Sung-Liang , Liou Jyh-Ming , Wu Deng-Chyang , Hou Ming-Chih , Wu Ming-Shiang , Wu Jiunn-Jong , Sung Joseph J Y , El-Omar Emad M , Wu Chun-Ying 
Published: February 2025

ObjectiveLive biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains ofAkkermansia muciniphilaandChristensenella minuta, as well as treatments using purified Firmicutes spores for recurrentClostridioides difficileinfections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.DesignExperts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.ResultsThe consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.ConclusionsThe development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.
Enhanced thrombopoiesis supplies PD-L1 to circulating immune cells via the generation of PD-L1-expressing platelets in patients with lung cancer
Authors: Lee Sung-Woo , Jeong Saei , Kim Young Ju , Noh Jeong Eun , Rho Kyung Na , Kim Hee-Ok , Cho Hyun-Ju , Yang Deok Hwan , Hwang Eu Chang , Kyun Bae Woo , Yun Sook Jung , Yun Ju Sik , Park Cheol-Kyu , Oh In-Jae , Cho Jae-Ho 
Published: February 2025

BackgroundThe increased expression of programmed cell death ligand 1 (PD-L1) on a subset of immune cells in the peripheral blood has been frequently observed in patients with cancer, suggesting a relationship with PD-L1 expression in tumor tissues. In this study, we investigated the mechanisms underlying PD-L1 expression on various types of immune cells in the peripheral blood of patients with cancer.MethodsPD-L1 expression on various immune cell populations was analyzed in peripheral blood mononuclear cells of 112 patients with non-small cell lung cancer (NSCLC) using flow cytometry. A mouse model of X-ray-induced acute thrombocytopenia was used to investigate the relationship between thrombopoiesis and PD-L1-expressing platelet generation. The clinical significance of PD-L1-expressing platelets was analyzed in a cohort of patients with stage IV NSCLC who received a combination of anti-programmed cell death 1 (PD-1) therapy and chemotherapy.ResultsAll immune cell populations, including monocytes, T cells, B cells, and NK cells, showed higher PD-L1 expression in patients with cancer than in healthy controls. However, this increased frequency of PD-L1-expressing cells was not attributed to the expression of the cells themselves. Instead, it was entirely dependent on the direct interaction of the cells with PD-L1-expressing platelets. Notably, the platelet-dependent acquisition of PD-L1 on circulating immune cells of patients with lung cancer was observed in various other cancer types and was mechanistically associated with a surge in thrombopoiesis, resulting in the increased production of PD-L1-expressing reticulated platelets. Clinically, patients with enhanced thrombopoiesis and concurrently high PD-L1-expressing platelets exhibited a better response to anti-PD-1 therapy.ConclusionsThese findings highlight the role of tumor-associated thrombopoiesis in generating PD-L1-expressing platelets that may serve as a resource for PD-L1-positive cells in the circulation and act as a predictive biomarker for anti-PD-1/PD-L1 therapy.
Impact of an intervention for osteoarthritis based on exercise and education on metabolic health: a register-based study using the SOAD cohort
Authors: Battista Simone , Recenti Filippo , Kiadaliri Ali , Lohmander Stefan , Jönsson Thérése , Abbott Allan , Vinblad Johanna , Rolfson Ola , Englund Martin , Dell’Isola Andrea 
Published: February 2025

ObjectiveThis study evaluated the effects of a 6-week osteoarthritis (OA) exercise and education intervention on metabolic health markers, including blood pressure (BP), glycated haemoglobin (HbA1c), high-density lipoprotein (HDL), cholesterol levels and weight in individuals with both OA and diabetes.MethodsData originated from the Swedish Osteoarthritis and Diabetes cohort, which is composed of the Swedish Osteoarthritis Register (SOAR) and National Diabetes Register. We included individuals diagnosed with OA and diabetes who underwent the intervention between January 2008 and December 2019, matched with controls with diabetes who did not based on birth year, sex, OA site (hip/knee) and OA diagnosis year. Outcomes included BP, HbA1c, HDL, total cholesterol levels and weight measured up to 3 years before and after SOAR enrolment. Statistical analyses used two-way fixed-effect models.ResultsThe study included 4571 individuals with OA and diabetes (mean age: 69.5, SD: 7.8; women: 52.7%; knee OA: 71.2%) and 7925 controls. The intervention group showed a systolic BP decrease of approximately 1.0 mm Hg at 6 and 12 months compared with the control group. HDL levels increased by about 0.02 mmol/L at 12, 18 and 24 months. Weight decreased by approximately 0.5 kg at 6, 18 and 30 months. HbA1c levels increased by approximately 0.5 mmol/mol at 6 months. No essential differences were found in the total cholesterol levels.ConclusionAn OA exercise and education intervention designed following OA clinical practice guidelines led to small and unlikely clinically relevant improvements in metabolic health markers in individuals with OA and diabetes.