bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda: stakeholder engagement meeting report
Authors: Hill Jenny ,   PDMC Saves Lives Consortium, Accrombessi Manfred , Briand Valérie , Dhabangi Aggrey , Hill Jenny , Hoyt Jenna , Idro Richard , Khairallah Carole , Kariuki Simon , ter Kuile Feiko O. , Kwambai Titus , Luty Adrian J. F. , Manda-Taylor Lucinda , Massougbodji Achille , Otieno Juliet , Phiri Kamija S. , Rosu Laura , Rujumba Joseph , Seddon Tracy , Tangara Brian , Vincent Jeanne Perpétue , Worrall Eve 
Published: March 2024

AbstractA Stakeholder engagement meeting on the implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda was held in Nairobi, Kenya, on 27 September 2023. Representatives from the respective National Malaria Control Programmes, the World Health Organization (WHO) Geneva, Africa Regional and Kenya offices, research partners, non-governmental organizations, and the Medicines for Malaria Venture participated. PDMC was recommended by the WHO in June 2022 and involves provision of a full anti-malarial treatment course at regular intervals during the post-discharge period in children hospitalized with severe anaemia in areas of moderate-to-high malaria transmission. The WHO recommendation followed evidence from a meta-analysis of three clinical trials and from acceptability, delivery, cost-effectiveness, and modelling studies. The trials were conducted in The Gambia using monthly sulfadoxine-pyrimethamine during the transmission season, in Malawi using monthly artemether-lumefantrine, and in Kenya and Uganda using monthly dihydroartemisinin-piperaquine, showing a significant reduction in all-cause mortality by 77% (95% CI 30–98) and a 55% (95% CI 44–64) reduction in all-cause hospital readmissions 6 months post-discharge. The recommendation has not yet been implemented in sub-Saharan Africa. There is no established platform for PDMC delivery. The objectives of the meeting were for the participating countries to share country contexts, plans and experiences regarding the adoption and implementation of PDMC and to explore potential delivery platforms in each setting. The meeting served as the beginning of stakeholder engagement within the PDMC Saves Lives project and will be followed by formative and implementation research to evaluate alternative delivery strategies in selected countries. Meeting highlights included country consensus on use of dihydroartemisinin-piperaquine for PDMC and expansion of the target group to "severe anaemia or severe malaria", in addition to identifying country-specific options for PDMC delivery for evaluation in implementation research. Further exploration is needed on whether the age group should be extended to school-age children.
The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers
Authors: Luo Qin , Chen Jingfei , Yi Yanfeng , Wu Panyun , Su Yingjie , Chen Zhangling , Aydemir Hacı Ahmet , Tang Jianjun , Fang Zhenfei , Luo Fei 
Published: March 2024

Abstract
Background and aims
Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD).

Methods
The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics.

Results
Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (β = 0.86, P < 0.001) and WBC (β = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients.

Conclusion
Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.
Opportunities for cancer prevention at syringe services programs: acceptability of HPV self-sampling and vaccination among people who inject drugs
Authors: Hinkes Samuel , Ciraldo Katrina , Kobetz Erin , Bartholomew Tyler S. , Rinehart Sarah , Siringo Nicolette , Barnett Rebecca , Godbole Neha , Jeanty Frantzia , Frederick Morgan , Tookes Hansel E. 
Published: March 2024

Abstract
Introduction
Despite having a high risk of acquiring sexually transmitted infections, people who inject drugs (PWID) often do not receive recommended HPV screenings due to barriers to healthcare. Guideline-based cervical HPV screening and vaccination can prevent cervical cancer. Low-cost, low-barrier methods for cancer screening and prevention are important for vulnerable communities such as PWID.

Methods
We examined acceptability of HPV self-sampling at a syringe services program (SSP). Participants with a cervix (n = 49) participated in patient education followed by a survey to assess willingness to perform HPV self-sampling versus standard of care.

Results
59% found self-sampling to be acceptable, citing privacy, ease, and quickness. Among those opting for HPV screening delivered by a provider (n = 16), participants cited concerns about adequate sampling (81%) and test accuracy (75%). Notably, only 18% of participants reported complete HPV vaccination.

Conclusion
Cervical HPV self-sampling was acceptable to PWID. SSP-based efforts to provide preventative health services could place tools for cancer screening into the hands of PWID, a need-to-reach community.
Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years
Authors: Salvador Christina , Salvador Robert , Kropshofer Gabriele , Meister Bernhard , Rock Marie , Obexer Petra , Hetzer Benjamin , Rabensteiner Evelyn , Crazzolara Roman 
Published: March 2024

Abstract
Background
Thromboembolic complications are well known in the treatment of childhood acute lymphoblastic leukemia. Over the years it has not been possible to reach a consensus on a possible prophylaxis of thromboembolic events during intensive therapy. Only the administration of enoxaparin was able to achieve evidence in the literature to date.

Methods
In this retrospective study, 173 childhood leukemia patients were treated over 20 years with a thromboembolic prophylaxis including enoxaparin and AT III during induction therapy with L-asparaginase and cortisone.

Results
We here report the effectiveness of administration of enoxaparin and AT III in childhood leukemia, showing a strikingly low prevalence of deep vein thrombosis (2.9%). Especially in adolescent patients, a particularly great need for AT III was demonstrated.

Conclusions
We recommend thromboembolic prophylaxis with enoxaparin and AT III substitution during induction/reinduction therapy with L-asparaginase and glucocorticosteroids, especially from adolescence onwards.
Rolapitant treats lung cancer by targeting deubiquitinase OTUD3
Authors: Du Tongde , Gu Quan , Zhang Yonghui , Gan Yujie , Liang Rongrui , Yang Wenzhu , Lu Ya , Xu Chenxin , Wu Jianzhong , Ma Rong , Cao Haixia , Jiang Jingwei , Wang Juan , Feng Jifeng 
Published: March 2024

Abstract
Background
Lung cancer is cancer with the highest morbidity and mortality in the world and poses a serious threat to human health. Therefore, discovering new treatments is urgently needed to improve lung cancer prognosis. Small molecule inhibitors targeting the ubiquitin-proteasome system have achieved great success, in which deubiquitinase inhibitors have broad clinical applications. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer.

Results
In this study, we identified a small molecule inhibitor of OTUD3, Rolapitant, by computer-aided virtual screening and biological experimental verification from FDA-approved drugs library. Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3. Quantitative proteomic profiling indicated that Rolapitant significantly upregulated the expression of death receptor 5 (DR5). Rolapitant also promoted lung cancer cell apoptosis through upregulating cell surface expression of DR5 and enhanced TRAIL-induced apoptosis. Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis. In the vivo assays, Rolapitant suppressed the growth of lung cancer xenografts in immunocompromised mice at suitable dosages without apparent toxicity.

Conclusion
In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer.
Osteofibrous dysplasia: a narrative review
Authors: Liu Rui , Tong Linjian , Wu Haiyang , Guo Qiang , Xu Lixia , Sun Zhiming , Yan Hua 
Published: March 2024

AbstractOsteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment.
Deep learning in cancer genomics and histopathology
Authors: Unger Michaela , Kather Jakob Nikolas 
Published: March 2024

AbstractHistopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. In this review, we summarize current and emerging applications of DL in histopathology and genomics, including basic diagnostic as well as advanced prognostic tasks. Based on a growing body of evidence, we suggest that DL could be the groundwork for a new kind of workflow in oncology and cancer research. However, we also point out that DL models can have biases and other flaws that users in healthcare and research need to know about, and we propose ways to address them.
Peptidoglycan in osteoarthritis synovial tissue is associated with joint inflammation
Authors: Holub Meaghan N , Wahhab Amanda , Rouse Joseph R , Danner Rebecca , Hackner Lauren G , Duris Christine B , McClune Mecaila E , Dressler Jules M , Strle Klemen , Jutras Brandon L , Edelstein Adam I , Lochhead Robert B 
Published: March 2024

Abstract
Objectives
Peptidoglycan (PG) is an arthritogenic bacterial cell wall component whose role in human osteoarthritis is poorly understood. The purpose of this study was to determine if PG is present in synovial tissue of osteoarthritis patients at the time of primary total knee arthroplasty (TKA), and if its presence is associated with inflammation and patient reported outcomes.

Methods
Intraoperative synovial tissue and synovial fluid samples were obtained from 56 patients undergoing primary TKA, none of whom had history of infection. PG in synovial tissue was detected by immunohistochemistry (IHC) and immunofluorescence microscopy (IFM). Synovial tissue inflammation and fibrosis were assessed by histopathology and synovial fluid cytokine quantification. Primary human fibroblasts isolated from arthritis synovial tissue were stimulated with PG to determine inflammatory cytokine response.

Results
A total of 33/56 (59%) of primary TKA synovial tissue samples were positive for PG by IHC, and PG staining colocalized with markers of synovial macrophages and fibroblasts by IFM. Synovial tissue inflammation and elevated IL-6 in synovial fluid positively correlated with PG positivity. Primary human fibroblasts stimulated with PG secreted high levels of IL-6, consistent with ex vivo findings. Interestingly, we observed a significant inverse correlation between PG and age at time of TKA, indicating younger age at time of TKA was associated with higher PG levels.

Conclusion
Peptidoglycan is commonly found in synovial tissue from patients undergoing TKA. Our data indicate that PG may play an important role in inflammatory synovitis, particularly in patients who undergo TKA at a relatively younger age.
Utility of the Venous Excess Ultrasound (VEXUS) score to track dynamic change in volume status in patients undergoing fluid removal during haemodialysis – the ACUVEX study
Authors: Wong Adrian , Olusanya Olusegun , Watchorn Jim , Bramham Kate , Hutchings Sam 
Published: March 2024

Abstract
Background
The use of ultrasound assessment, including the Venous Excess Ultrasound (VEXUS) score, is increasingly being utilised as part of fluid status assessment in clinical practice. We aimed to evaluate the ability of the VEXUS score to track fluid removal during the course of the dialysis session and explore the relationship between traditional measures of fluid status and venous congestion.

Methods
Single-centre, observational study in patients undergoing intermittent haemodialysis, who presented above their target dry weight. Patients had serial assessment using VEXUS, lung ultrasound and selected echocardiographic measures, before, during and after fluid removal.

Results
Amongst 33 patients analysed, 5 (15%) had an elevated VEXUS score (> 0). There was no difference in starting weight, dry weight or amount of fluid removed in patients with a normal VEXUS score and those with an elevated VEXUS score. In all patients with elevated VEXUS scores, the degree of venous congestion improved during the course of fluid removal. All patients with an elevated VEXUS score had evidence of both right and left ventricular systolic impairment.

Conclusion
In patients with ESRF undergoing haemodialysis, the incidence of venous congestion as measured by the VEXUS is low. In patients with elevated VEXUS scores, removal of fluid through haemodialysis improves the venous congestion score. The pattern of LV and RV systolic dysfunction suggests that VEXUS may be a reflection of cardiac failure rather than venous volume status.

Trial registration
Ethical approval was provided by South Central-Berkshire Research and Ethics Committee and registered on clinicaltrials.org (IRAS305720). Trial registration: ISRCTN14351189 – Retrospectively registered on 30/11/2023.
Elevated tryptase level in a child with idiopathic anaphylaxis: a case of hereditary alpha-tryptasemia
Authors: Le Blanc Vicky , Watson Wade T. A. 
Published: March 2024

AbstractHereditary alpha-tryptasemia (HαT) is an autosomal dominant disorder estimated to affect 5% of the population. High baseline tryptase level is a consistent finding, but there is a great variability of clinic manifestations, including no symptoms at all. We describe a case of HαT in a 5 years 8 months old girl manifesting with idiopathic anaphylaxis and elevated baseline tryptase level. As more cases of HαT are described, a better understanding of the clinical phenotype will be acquired.
The paradox of MRI for breast cancer screening: high-risk and dense breasts—available evidence and current practice
Authors: Sardanelli Francesco , Magni Veronica , Rossini Gabriele , Kilburn-Toppin Fleur , Healy Nuala A. , Gilbert Fiona J. 
Published: March 2024

AbstractIn the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25−58% for mammography, 33−52% for ultrasound, 48−67% for mammography plus ultrasound, and 71−100% for MRI; specificity 93–100%, 91–98%, 89–98%, and 81–98%, respectively. Based on the available evidence, in 2006–2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the “DENSE” RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.Key points• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory.
Graphical Abstract
Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives
Authors: Yuan Chenrui , Song Wei , Jiang Xiping , Wang Yifei , Li Chenkai , Yu Weilin , He Yaohua 
Published: March 2024

AbstractMusculoskeletal disorders are the leading causes of physical disabilities worldwide. The poor self-repair capacity of musculoskeletal tissues and the absence of effective therapies have driven the development of novel bioengineering-based therapeutic approaches. Adipose-derived stem cell (ADSC)-based therapies are being explored as new regenerative strategies for the repair and regeneration of bone, cartilage, and tendon owing to the accessibility, multipotency, and active paracrine activity of ADSCs. In this review, recent advances in ADSCs and their optimization strategies, including ADSC-derived exosomes (ADSC-Exos), biomaterials, and genetic modifications, are summarized. Furthermore, the preclinical and clinical applications of ADSCs and ADSC-Exos, either alone or in combination with growth factors or biomaterials or in genetically modified forms, for bone, cartilage, and tendon regeneration are reviewed. ADSC-based optimization strategies hold promise for the management of multiple types of musculoskeletal injuries. The timely summary and highlights provided here could offer guidance for further investigations to accelerate the development and clinical application of ADSC-based therapies in musculoskeletal regeneration.
Graphical abstract
The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles
Authors: Song Yinhua , Wu Jiachen , Liu Yang , Xu Na , Bai Hualin , Wang Lingjuan , Ai Jihui , Li Kezhen 
Published: March 2024

AbstractPremature ovarian insufficiency (POI) is an essential cause of reduced fertility and quality of life in young women. Mesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have the ability to migrate to damaged tissues and are considered as promising therapeutic approaches for POI. However, the homing ability and therapeutic efficacy of MSCs administered in vivo are still insufficient, and their potential tumorigenicity and multi-differentiation potential also bring many doubts about their safety. The targeting ability and migration efficiency of MSCs can be improved by genetic engineering and surface modification, thereby maximizing their therapeutic efficacy. However, the use of viral vectors also has increased safety concerns. In addition, EVs, which seem to be the current therapeutic alternative to MSCs, are still poorly targeted for distribution, although they have improved in terms of safety. This paper reviews the comparative therapeutic effects of MSCs and their derived EVs on POI, their biodistribution after in vivo administration, and the most important possible ovarian targeting strategies. Difficulties such as homogeneity and yield before clinical application are also discussed. This article will provide new insights into precision therapy and targeted drug delivery for female ovarian diseases.
Graphical Abstract