bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tubal flushing with oil-based contrast during hysterosalpingography versus tubal flushing by hysterosalpingo-foam sonography in infertile women undergoing fertility work-up: study protocol of a randomised controlled trial (FOil study)
Authors: Kamphuis Danah , Huijser Janette P M , van Welie Nienke , Verhoeve Harold R , Kuijper Esther , de Bruin Jan Peter , van Dongen Angelique J C M , Gielen Susanne C J P , de Krom Guusje , Janse Femi , Koks Carolien A M , Nap Annemiek W , Anema Johannes R , Bosmans Judith E , Stoker Jaap , van Wely Madelon , Mol Ben Willem J , Mijatovic Velja , Dreyer Kim 
Published: November 2024

IntroductionHysterosalpingography (HSG) and hysterosalpingo-foam sonography (HyFoSy) are commonly used tubal patency tests during the fertility work-up. Besides its diagnostic purpose, HSG with oil-based contrast can also be applied for its fertility-enhancing effect, by tubal flushing. HyFoSy is considered as less painful compared with HSG, it lacks exposure to iodinated contrast medium and ionising radiation. The fertility-enhancing effects of HyFoSy are less studied and randomised controlled trials comparing pregnancy rates after HSG and HyFoSy are lacking. This study (FOil study) is initiated to compare the effectiveness of tubal flushing during HSG with oil-based contrast and HyFoSy.Methods and analysisThe FOil study is a nationwide, multicentre, open label, randomised controlled trial with a superiority design. Infertile women with an indication for tubal patency testing during their fertility work-up will be randomly assigned to HSG with oil-based contrast medium or HyFoSy. The primary outcome is conception within 6 months after randomisation leading to live birth. To demonstrate or refute an 8% difference in conception leading to live birth in favour of HSG with oil-based contrast, 1102 women will be included in the trial. A cost-effectiveness analysis from a societal perspective will be performed alongside the trial.Ethics and disseminationThe trial is approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers (Ref. No. 2022.0884, date: 17 March 2023) and by the boards of the participating hospitals. The findings will be disseminated in peer-reviewed journals and participants will be informed through the patient organisation.Trial registration numberNCT05882188.
Plasmodium falciparummolecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol
Authors: da Silva Clemente , Matambisso Gloria , Boene Simone , Rovira-Vallbona Eduard , Pujol Arnau , Comiche Kiba , Sánchez Antoni , Greenhouse Bryan , Chidimatembue Arlindo , Aranda-Díaz Andrés , Arnaldo Paulo , Ariani Cristina , Walker Patrick , Mbeve Henriques , Ndimande Nelo , Tembisse Dário , Ruybal-Pesántez Shazia , Verity Robert , Rafael Bernardete , Candrinho Baltazar , Mayor Alfredo 
Published: November 2024

IntroductionMalaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023–2030) for malaria control and elimination.Methods and analysesThis prospective genomic surveillance study aims to generatePlasmodium falciparumgenetic data to monitor diagnostic failures due topfhrp2/3deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination). The study, to be conducted between 2024 and 2026, will use three sampling schemes: a multicluster probabilistic health facility survey in the 10 provinces of the country to detectpfhrp2/3deletions and markers of antimalarial drug resistance; dense sampling of all clinical cases in representative districts in the south targeted for elimination to characterise malaria importation and identify sources of transmission; and testing of pregnant women for malaria at their first antenatal care visit to assess malaria burden and molecular trends. Using a multiplex amplicon-based sequencing approach, the study will target microhaplotypes informative of genomic diversity and relatedness, as well as key drug resistance-associated genes,pfhrp2/3deletion and malaria vaccine targets. Key genomic information will be visualised in a dashboard integrated into the District Health Information System V.2-based Malaria Information Storage System for programmatic use.Ethics and disseminationThe protocol was reviewed and approved by the national ethics committee of Mozambique (Comité Nacional de Bioética para Saúde, Ref: 680/CNBS/23). Project results will be presented to all stakeholders using study-specific brochures and published in open-access journals.Trial registration numberNCT06529237.
Study protocol: Return to Country, an Australia-wide prospective observational study about returning First Nations renal patients home
Authors: Jones Yomei , Truong Mandy , Preece Cecilia , Cass Alan , Heerink Fiona , McDonald Stephen , Jones Scott , Mallett Andrew John , Majoni Sandawana William , Sajiv Cherian , Patankar Khalil , Mulholland Eddie , Woldeyohannes Solomon , Lawton Paul 
Published: November 2024

IntroductionIn Australia, kidney failure treatment disparities exist between Aboriginal and/or Torres Strait Islander (First Nations) and non-First Nations people. Despite persistent calls from First Nations patients with kidney failure, they are less likely to have treatment that allows them to live at home.Methods and analysisThis is a prospective, multicentre study based in Australia. The aim of the study is to characterise the socioeconomic, environmental, health service and biomedical factors driving the health outcomes and patterns of health service utilisation experienced by First Nations patients and investigate whether health service changes to address these identified barriers can achieve higher rates of renal replacement therapy at home on country. This will be achieved by mixed-methods data collection at health service (audit and process data), staff (surveys and qualitative interviews) and patient (survey testing, feedback sessions, health outcomes) levels. A process evaluation will identify barriers and enablers to health services changes in relation to cultural safety. Baseline and follow-up data will be compared to assess the extent to which health services change their service delivery and the impact on health outcomes for First Nations patients with kidney failure. Qualitative and quantitative data will be integrated to provide an in-depth understanding of project outcomes and impacts.Ethics and disseminationThis study is funded by the National Health and Medical Research Council of Australia (GNT1158075). Ethics approval has been obtained so far from the Human Research Ethics Committee (HREC) of the Northern Territory Department of Health and Menzies School of Health Research (2019-3530), Far North Queensland HREC (2023/QCH/99606 (Nov ver 4)-1732), the Central Adelaide Local Health Network HREC (2023/HRE00209), the Aboriginal Health Council of South Australia (AHREC Protocol #: 04-23-1078), the Aboriginal Health and Medical Research Council of New South Wales (AH&MRC HREC reference: 2230/24) and the Far North Queensland Human Research Ethics Committee (FNQ HREC reference: HREC/2023/QCH/99606 (Nov ver 4)-1732). Study participants, policy makers and community organisations will be provided with updates of study findings. Dissemination of study findings will be through peer-reviewed publications and conference presentations.Trial registration numberACTRN12623001241628.
Implementing group consultations in a lower limb musculoskeletal outpatient service to improve efficiency and maintain positive patient outcomes
Authors: Wigham Lisa , Richardson Annette , Moore Kathryn , Martin Michael 
Published: November 2024

BackgroundGroup consultations (GCs) in healthcare have been shown to improve clinical outcomes with greater efficiency. This project aimed to develop a more efficient musculoskeletal (MSK) physiotherapy-led GC approach for common lower limb problems. This was to help manage an anticipated increase in demand while maintaining high patient satisfaction and ensuring clinical effectiveness.MethodsThree ‘Plan-Do-Study-Act’ (PDSA) cycles were undertaken to test out the new approach of virtual group consultations (VGCs) and face-to-face GCs with MSK patients. These two approaches were tested and refined on four common lower limb conditions: patellofemoral pain syndrome, Achilles tendinopathy, plantar fasciopathy and knee osteoarthritis. We measured the number of patients seen, staff time, patients’ experience and patient outcome scores.ResultsEach patient used 45 min of physiotherapy time via the traditional one-to-one physiotherapy consultation approach, this was reduced to 22 min in the VGCs and 12 min for the face-to-face GCs. We found a significant increase in EQ-5D scores (PDSA 1: +0.19, p=0.004 and PDSA 2: +0.17, p=0.002) and the Visual Analogue Score for Pain (PDSA 1: −1.95, p=0.001 and PDSA 2: −2.6, p=0.007) from the first to the second virtual GC sessions.ConclusionGCs were shown to be an efficient way of providing physiotherapy to patients with lower limb conditions. Feedback from patients attending GCs has shown a good level of effectiveness and patient satisfaction. This alternative way to review and treat patients has yielded a reduction in physiotherapist contact time per patient, improving the efficiency of our MSK service. We did not compare these groups to the one-to-one face-to-face consultations, therefore whether they are better, is unknown.
Life course socio-demographic circumstances and the association between housing tenure and disability-free life expectancy in Australia: a longitudinal cohort study
Authors: Hambisa Mitiku Teshome , Kiely Kim M 
Published: November 2024

IntroductionThis study aimed to assess the extent to which the association between housing tenure and disability-free life years is independent of socio-demographic circumstances from earlier in life.MethodsWe analysed nationally representative data from the Household Income and Labour Dynamics in Australia survey. Participants were followed up for 14 years (2001–2014). Housing tenure was measured by the question, “Do you (or any other members of this household) own this home, rent it, or do you live here rent-free?” Disability was defined by the SF-36 physical function subscale. We used multistate modelling and inverse probability weighting to estimate the association between housing tenure (home ownership vs renting) and disability-free life expectancy (DFLE), adjusting for a range of socio-demographic indicators.ResultsThe sample included 6164 participants (52.5% women) aged 45 years and older in 2001. In weighted analyses that adjusted for earlier life circumstances, for men, the estimated total life expectancy (TLE) at age 65 among renters was 16.7 years, 2.3 (95% CI −3.7 to −0.7) years shorter than the TLE of 19.0 years for owner-occupiers. DFLE was 1.8 years shorter for renters than owner-occupiers. For women at age 65, the weighted TLE was estimated to be 20.6 years, 2.3 (95% CI −3.9 to −0.6) years shorter than the 22.9 years estimated for owner-occupiers. Compared with owner-occupiers, DFLE was 3.1 years shorter for women renters.ConclusionsBoth men and women renters had shorter disability-free and TLE than owner-occupiers independent of earlier life circumstances. There is a need for policies addressing potential health disparities linked to housing tenure.
Burnout, motivation and job satisfaction among community health workers recruited for a depression training in Madhya Pradesh, India: a cross-sectional study
Authors: Mitchell Lauren M , Anand Aditya , Muke Shital , Hollon Steven D , Joshi Udita , Khan Azaz , Haney Juliana , Shrivastava Ritu , Singh Abhishek , Singla Daisy , Teja G Sai , Tugnawat Deepak , Bhan Anant , Patel Vikram , Naslund John A 
Published: November 2024

IntroductionBurnout, low motivation and poor job satisfaction among community health workers (CHWs) have negative impacts on health workers and on patients. This study aimed to characterise levels of burnout, motivation and job satisfaction in CHWs in Madhya Pradesh, India and to determine the relation between these levels and participant characteristics. This study can inform efforts to promote well-being and address stress in this population.MethodsIn this cross-sectional study, we recruited participants via simple random sampling without replacement. We administered two validated questionnaires, the Copenhagen Burnout Inventory and a Motivation and Job Satisfaction Assessment, to CHWs who had enrolled in a training programme to deliver a brief psychological intervention for depression. We calculated mean scores for each questionnaire item, examined the reliability of the measures and analysed associations between participant demographic characteristics and questionnaire scores.Results339 CHWs completed the questionnaires. The personal burnout domain had the highest mean burnout score (41.08, 95% CI 39.52 to 42.64, scale 0–100) and 33% of participants reported moderate or greater levels of personal burnout. Items that reflected physical exhaustion had the highest item-test correlations. The organisation commitment domain had the highest mean motivation score (mean 3.34, 95% CI 3.28 to 3.40, scale 1–4). Items describing pride in CHWs’ work had the highest item-test correlations. Several pairwise comparisons showed that higher education levels were associated with higher motivation levels (degree or higher vs eighth standard (p=0.0044) and 10th standard (p=0.048) and 12th standard versus eighth standard (p=0.012)). Cronbach’s alpha was 0.82 for the burnout questionnaire and 0.86 for the motivation and job satisfaction questionnaire.ConclusionCHWs report experiencing burnout and feeling physically tired and worn out. A sense of pride in their work appears to contribute to motivation. These findings can inform efforts to address burnout and implement effective task-sharing programmes in low-resource settings.
Prospective cohort study exploring the neurodevelopmental outcomes following documented neonatal sepsis in Nepal: study protocol
Authors: Vaidya Swechhya , Raj Manu , Sudevan Remya , Chandramathi Jayasree , Karmacharya Shailendra Bir , Subedi Kalpana , Raya Ganendra Bhakta , Shrestha Dhruba 
Published: November 2024

IntroductionNeonatal sepsis, a significant contributor to global neonatal mortality, poses substantial risks to infant health, particularly in low-resource countries like Nepal. Despite its high prevalence, there is a lack of clarity in defining and understanding neonatal sepsis, leading to challenges in diagnosing and managing the condition effectively. The probable impact of neonatal sepsis on long-term neurodevelopmental outcomes, including motor and cognitive delays, remains under-explored in Nepal. The primary objective of this study is to report the prevalence of neurodevelopmental delay in neonates with documented sepsis. The secondary objective is to report significant associations of the same with selected probable risk factors.Methods and analysisThis is a dual-centric prospective cohort study that is ongoing at two hospitals—Paropakar Maternity and Women’s Hospital and Siddhi Memorial Hospital in Nepal, over a 2-year period. Neonates diagnosed with sepsis will be assessed using the Developmental Assessment Scale for Indian Infants at 6 months and 1 year, postdiagnosis. Statistical analyses will include prevalence estimation and logistic regression.
Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma
Authors: Zhou Qian , Dian Yating , He Yi , Yao Lei , Su Hui , Meng Yu , Sun Yuming , Li Daishi , Xiong Yixiao , Zeng Furong , Liang Xiaowei , Liu Hong , Chen Xiang , Deng Guangtong 
Published: November 2024

BackgroundDespite the successful application of immunotherapy, both innate and acquired resistance are typical in melanoma. Ferroptosis induction appears to be a potential strategy to enhance the effectiveness of immunotherapy. However, the relationship between the status of ferroptosis and the effectiveness of immunotherapy, as well as viable strategies to augment ferroptosis, remains unclear.MethodsA screening of 200 cardiovascular drugs obtained from the Food and Drug Administration-approved drug library was conducted to identify the potential ferroptosis sensitizer. In vitro and in vivo experiments explored the effects of propafenone on ferroptosis in melanoma. Animal models and transcriptomic analyses evaluated the therapeutic effects and survival benefits of propafenone combined with immune checkpoint blockades (ICBs). The relationship between propafenone targets and the efficacy of ICBs was validated using the Xiangya melanoma data set and publicly available clinical data sets.ResultsThrough large-scale drug screening of cardiovascular drugs, we identified propafenone, an anti-arrhythmia medication, as capable of synergizing with ferroptosis inducers in melanoma. Furthermore, we observed that propafenone, in combination with glutathione peroxidase 4 inhibitor RSL3, collaboratively induces mitochondrial-associated ferroptosis. Mechanistically, propafenone transcriptionally upregulates mitochondrial heme oxygenase 1 through the activation of the Jun N-terminal kinase (JNK)/JUN signaling pathway under RSL3 treatment, leading to overloaded ferrous iron and reactive oxygen species within the mitochondria. In xenograft models, the combination of propafenone and ferroptosis induction led to nearly complete tumor regression and prolonged survival. Consistently, propafenone enhances immunotherapy-induced tumorous ferroptosis and antitumor immunity in tumor-bearing mice. Significantly, patients exhibiting high levels of ferroptosis/JUN/HMOX1 exhibited improved efficacy of immunotherapy and prolonged progression-free survival.ConclusionsTaken together, our findings suggest that propafenone holds promise as a candidate drug for enhancing the efficacy of immunotherapy and other ferroptosis-targeted therapies in the treatment of melanoma.
Neoadjuvant immunotherapy in the evolving landscape of sarcoma treatment
Authors: Cai Qiyan , Que Yi , Zhang Xing 
Published: November 2024

AbstractSoft tissue sarcoma is characterized by its rarity and complexity, making it more difficult to conduct large clinical trials compared with other solid tumors. Also known as ‘cold tumors,’ sarcomas, especially advanced sarcomas, have poor responses to immunotherapy. Based on that, the results of two groundbreaking phase 2 clinical trials about neoadjuvant immunotherapy in patients with liposarcoma or undifferentiated pleomorphic sarcoma are encouraging. In this paper, we discuss the results of these clinical trials and the challenges we are facing to conduct neoadjuvant immunotherapy in sarcomas and call for further research to promote the development of it.
Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy
Authors: Li Tianhao , Guo Shengnan , Xu Chang , Zhang Mingjie , Lyu Cheng , Xu Huanhuan , Hou Zepeng , Zhang Mingshuo , Li Xiaobo , Ren Jing , Liu Changqing , Kong Dan , Hao Dapeng , Wang Guangyu 
Published: November 2024

BackgroundDespite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further mechanistic understanding of therapy response.MethodsWe comprehensively analyzed paired single-cell RNA transcriptome and T-cell repertoire profiles from 14 HCC ascites samples, collected from 7 patients before and after treatment with the combination of sintilimab (anti-PD-1) and bevacizumab (anti-VEGF).ResultsWe identify a widespread convergence on interferon (IFN) signaling across various immune cell lineages in treatment-responsive patients with HCC, indicating a common transcriptional state transition in the immune microenvironment linked to immunotherapy response in HCC. Strong IFN signaling marks CD8+T cells with larger clonal expansion and enhanced cytotoxicity, macrophages toward M1-like polarization and strong T-cell recruitment ability, dendritic cells with increased antigen presentation capacity, as well as highly cytotoxic natural killer cells and activated B cells. By translating our finding to cohorts of patients with HCC, we demonstrate the specificity of IFN-signaling in the prognosis of patients with HCC and its ability to predict immunotherapy response.ConclusionsThis study provides a unique single-cell resource with clonal and longitudinal resolution during ICI therapy and reveals IFN signaling as a biomarker of immunotherapy response in HCC, suggesting a beneficial effect by combining IFN inducers with ICIs for patients with HCC.
Treatment of iatrogenic vertebral artery injury during C1-C2 arthrodesis with a covered stent
Authors: Bram Richard , Mehta Ankit I , Atwal Gursant 
Published: November 2024

Iatrogenic vertebral artery injury (VAI) has been described in the context of both anterior and posterior approaches to the cervical spine.1 2 Endovascular treatment of VAI primarily entails vessel sacrifice or vascular reconstruction. The latter option offers the advantage of achieving hemostasis while maintaining parent vessel patency.3 In this video (video 1) we describe the case of a patient in their 20s undergoing C1-C2 arthrodesis with Harms technique. A V3 segment VAI was successfully treated with two overlapping covered stents which provided hemostasis and parent vessel reconstruction. Follow-up angiography demonstrated robust flow in the parent vertebral artery with no in-stent stenosis. The patient remained at neurological baseline with no ischemic or hemorrhagic complications. To our knowledge, this is the first technical video demonstrating this technique in the setting of iatrogenic VAI.Video 1 Endovascular treatment of iatrogenic vertebral artery injury with a covered stent.
Recurrent intrathecal catheter-tip granuloma formation on a replaced system delivering low dose/concentration fentanyl and bupivacaine: a case report
Authors: Feldheim Timothy V , Hayek Salim M 
Published: November 2024

BackgroundIntrathecal drug delivery (IDD) is a well-established treatment modality for refractory chronic pain. Intrathecal catheter-tip granuloma (ICTG) formation is a known possible complication of opiate IDD and is likely triggered by mast cell degranulation. The use of low concentration and dosage of opioids that do not induce mast cell degranulation has been advised to mitigate the risk of ICTG formation.Case presentationA patient in their 50s with history of multiple lumbar spine surgeries and refractory low back pain who was treated with IDD developed an initial ICTG while receiving intrathecal hydromorphone and bupivacaine. The patient’s catheter was thus replaced and repositioned. The pump was also replaced due to repeat motor stall, and the infusate was changed from hydromorphone with bupivacaine to low-dose fentanyl with bupivacaine. Five years later, the patient developed myelopathic symptoms, and on imaging a new mass believed to be an ICTG was detected at the new thoracic catheter tip location. The patient was placed on normal saline infusion for 4 months before system explant, with some improvement of symptoms.ConclusionsICTG formation is uncommon but can be a devastating complication of IDD if not properly diagnosed in a timely fashion. Repeat ICTG has only been documented twice in the literature, and ICTG with low dose fentanyl in combination with bupivacaine has not been reported. Despite using regimens and techniques to reduce the risk of ICTG formation, one must judiciously surveil their patients for the dreaded ICTG complication.