bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma
Authors: Tsai Yu-Fen , Chan Leong-Perng , Chen Yuk-Kwan , Su Chang-Wei , Hsu Ching-Wei , Wang Yen-Yun , Yuan Shyng-Shiou F. 
Published: October 2023

Abstract
Objectives
RAD51 overexpression has been reported to serve as a marker of poor prognosis in several cancer types. This study aimed to survey the role of RAD51 in oral squamous cell carcinoma and whether RAD51 could be a potential therapeutic target.

Materials and methods
RAD51 protein expression, assessed by immunohistochemical staining, was used to examine associations with survival and clinicopathological profiles of patients with oral squamous cell carcinoma. Lentiviral infection was used to knock down or overexpress RAD51. The influence of RAD51 on the biological profile of oral cancer cells was evaluated. Cell viability and apoptosis after treatment with chemotherapeutic agents and irradiation were analyzed. Co-treatment with chemotherapeutic agents and B02, a RAD51 inhibitor, was used to examine additional cytotoxic effects.

Results
Oral squamous cell carcinoma patients with higher RAD51 expression exhibited worse survival, especially those treated with adjuvant chemotherapy and radiotherapy. RAD51 overexpression promotes resistance to chemotherapy and radiotherapy in oral cancer cells in vitro. Higher tumorsphere formation ability was observed in RAD51 overexpressing oral cancer cells. However, the expression of oral cancer stem cell markers did not change in immunoblotting analysis. Co-treatment with RAD51 inhibitor B02 and cisplatin, compared with cisplatin alone, significantly enhanced cytotoxicity in oral cancer cells.

Conclusion
RAD51 is a poor prognostic marker for oral squamous cell carcinoma. High RAD51 protein expression associates with resistance to chemotherapy and radiotherapy. Addition of B02 significantly increased the cytotoxicity of cisplatin. These findings suggest that RAD51 protein may function as a treatment target for oral cancer.

Trial registration
Number: KMUHIRB-E(I)-20190009 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, approved on 20190130, Retrospective registration.
Injectable biocompatible nanocomposites of Prussian blue nanoparticles and bacterial cellulose as a safe and effective photothermal cancer therapy
Authors: Hong Hwichan , Kim MinKyu , Lee Wooseung , Jeon Miyeon , Lee Chaedong , Kim Hoonsub , Im Hyung-Jun , Piao Yuanzhe 
Published: October 2023

AbstractPhotothermal therapy (PTT) is a novel cancer treatment using a photoabsorber to cause hyperthermia to kill tumors by laser irradiation. Prussian blue nanoparticles (PB NPs) are considered as next-generation photothermal agents due to the facile synthesis and excellent absorption of near-infrared light. Although PB NPs demonstrate remarkable PTT capabilities, their clinical application is limited due to their systemic toxicity. Bacterial cellulose (BC) has been applied to various bio-applications based on its unique properties and biocompatibility. Herein, we design composites with PB NPs and BC as an injectable, highly biocompatible PTT agent (IBC-PB composites). Injectable bacterial cellulose (IBC) is produced through the trituration of BC, with PB NPs synthesized on the IBC surface to prepare IBC-PB composites. IBC-PB composites show in vitro and in vivo photothermal therapeutic effects similar to those of PB NPs but with significantly greater biocompatibility. Specifically, in vitro therapeutic index of IBC-PB composites is 26.5-fold higher than that of PB NPs. Furthermore, unlike PB NPs, IBC-PB composites exhibit no overt toxicity in mice as assessed by blood biochemical analysis and histological images. Hence, it is worth pursuing further research and development of IBC-PB composites as they hold promise as safe and efficacious PTT agents for clinical application.Graphical Abstract
Development of self-care strategies to promote young Iranian women’s sexual health: an explanatory sequential mixed method study protocol
Authors: Bonyadpour Batool , Maasoumi Raziyeh , Nekoolaltak Maryam 
Published: October 2023

Abstract
Background
In contemporary Iran, the nation's traditional and deeply religious society is currently experiencing swift transformations in its moral, cultural, and social aspects. It is, therefore, not surprising to observe shifts in people's attitudes toward sexuality, largely attributed to the profound impact of widespread social networks, the proliferation of information technology, and increased levels of education. Unmarried young women may potentially face adverse consequences from engaging in extramarital sexual relationships across various aspects of their lives. Acknowledging the pivotal role of self-care in influencing the sexual behaviors of young women, the objective of this study is to compile a comprehensive list of self-care strategies aimed at improving the sexual well-being of young, single Iranian women.

Methods
The research will unfold in three distinct phases: Phase 1: Explanatory Sequential Mixed-Method Study This initial phase encompasses both quantitative and qualitative aspects. It begins with a cross-sectional survey, where we will gather data from 400 unmarried female students aged 18 to 29 years, utilizing a cluster random sampling method at Kerman University of Medical Sciences. Data collection will involve the use of a researcher-designed questionnaire. Subsequently, the qualitative phase will involve conducting in-depth, semi-structured interviews with female students from the University. To analyze this qualitative data, we will employ the content analysis approach. The findings obtained from both phases will be combined. Phase 2: Narrative Review In the second stage of the study, we will conduct an extensive narrative review to explore existing strategies related to the subject matter comprehensively. This review will serve as the foundational basis for our subsequent analysis. Phase 3: Strategy Prioritization In the final phase, we will prioritize the proposed strategies using a nominal group process, soliciting expert advice. This step will result in the definitive list of strategies that emerge from the study.

Discussion
This study pioneers the field of sexual health, with the goal of developing a protocol for creating self-care strategies based on the perspectives of young, unmarried Iranian women. It offers potential evidence-based insights into current developments in the physical, psychological, and social aspects of sexual health within this demographic. Additionally, it aims to furnish essential information to healthcare policymakers regarding the sexual health of young women.
Genomic variant benchmark: if you cannot measure it, you cannot improve it
Authors: Majidian Sina , Agustinho Daniel Paiva , Chin Chen-Shan , Sedlazeck Fritz J. , Mahmoud Medhat 
Published: October 2023

AbstractGenomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.
MCProj: metacell projection for interpretable and quantitative use of transcriptional atlases
Authors: Ben-Kiki Oren , Bercovich Akhiad , Lifshitz Aviezer , Raz Ofir , Brook Dror , Tanay Amos 
Published: October 2023

AbstractWe describe MCProj—an algorithm for analyzing query scRNA-seq data by projections over reference single-cell atlases. We represent the reference as a manifold of annotated metacell gene expression distributions. We then interpret query metacells as mixtures of atlas distributions while correcting for technology-specific gene biases. This approach distinguishes and tags query cells that are consistent with atlas states from unobserved (novel or artifactual) behaviors. It also identifies expression differences observed in successfully mapped query states. We showcase MCProj functionality by projecting scRNA-seq data on a blood cell atlas, deriving precise, quantitative, and interpretable results across technologies and datasets.
Medicines and Healthcare products Regulatory Agency’s “Consultation on proposals for legislative changes for clinical trials”: a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing
Authors: Law Martin , Couturier Dominique-Laurent , Choodari-Oskooei Babak , Crout Phillip , Gamble Carrol , Jacko Peter , Pallmann Philip , Pilling Mark , Robertson David S. , Robling Michael , Sydes Matthew R. , Villar Sofía S. , Wason James , Wheeler Graham , Williamson S. Faye , Yap Christina , Jaki Thomas 
Published: October 2023

AbstractIn the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals “to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines”. The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing — making anonymised individual-level clinical trial data available to other investigators for further use — is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council’s Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.
Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design
Authors: Truthmann Julia , Freyer Martins Pereira Julia , Richter Adrian , Schuster Franziska , Witte Amelie , Böhm Susanne , Greser Alexandra , Kamin Petra , Stracke Sylvia , Dörr Marcus , Bülow Robin , Engeli Stefan , Gágyor Ildikó , Hummers Eva , Chenot Jean-François 
Published: October 2023

Abstract
Background
Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen.

Methods
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients’ global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed.

Discussion
This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care.

Trial registration
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680
Normalized economical speed is influenced by aging and not by exercise habituation
Authors: Horiuchi Masahiro , Saito Akira , Motoyama Kiyotaka , Tashiro Takehiro , Abe Daijiro 
Published: October 2023

Abstract
Objective
A U-shaped relationship between energy cost of walking (Cw) and walking speed indicates that there is a specific speed minimizing the Cw, called economical speed (ES). It is mostly slower in older adults than young adults; however, effects of leg length on the ES have been ignored. We investigated effects of aging and exercise habituation on the normalized ES by leg length (ESnormalized). We quantified time delay of stride length and step frequency in sedentary young (SY), active young (AY), and active elderly (AE) adults in response to sinusoidal gait speed change at 30-s and 180-s periods with an amplitude of ± 0.56 m･s− 1.

Results
The ES was significantly slower in the following sequence: AE, SY, and AY, whereas ESnormalized was slower in the AE than in other young groups, with no difference between AY and SY. AE and SY showed greater step variabilities at the 180-s period, whereas AY showed relatively smaller step variabilities at both periods. Collectively, the ESnormalized slowed due to aging, not due to exercise habituation. When optimizing the appropriate SL-SF combination for sinusoidal speed changes, young and elderly adults may adopt different strategies. Exercise habituation may reduce step variabilities in young adults.
A transgenic mice model of retinopathy of cblG-type inherited disorder of one-carbon metabolism highlights epigenome-wide alterations related to cone photoreceptor cells development and retinal metabolism
Authors: Matmat Karim , Conart Jean-Baptiste , Graindorge Paul-Henri , El Kouche Sandra , Hassan Ziad , Siblini Youssef , Umoret Rémy , Safar Ramia , Baspinar Okan , Robert Aurélie , Alberto Jean-Marc , Oussalah Abderrahim , Coelho David , Guéant Jean-Louis , Guéant-Rodriguez Rosa-Maria 
Published: October 2023

AbstractBackgroundMTRgene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions.cblGtype of inherited disorders of vitamin B12 metabolism due to mutations inMTRgene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies.MethodsTo unveil the underlying epigenetic pathological mechanisms, we conducted a comprehensive study of epigenomic-wide alterations of DNA methylation by NGS of bisulfited retinal DNA in an original murine model with conditionalMtrdeletion in retinal tissue. Our focus was on postnatal day 21, a critical developmental juncture for ocular structure refinement and functional maturation.ResultsWe observed delayed eye opening and impaired visual acuity and alterations in the one-carbon metabolomic profile, with a notable dramatic decline in SAM/SAH ratio predicted to impair DNA methylation. This metabolic disruption led to epigenome-wide changes in genes involved in eye development, synaptic plasticity, and retinoid metabolism, including promoter hypermethylation ofRarα, a regulator ofLratexpression. Consistently, we observed a decline in cone photoreceptor cells and reduced expression ofLrat,Rpe65,andRdh5, three pivotal genes of eye retinoid metabolism.ConclusionWe introduced an original in vivo model for studyingcblGretinopathy, which highlighted the pivotal role of altered DNA methylation in eye development, cone differentiation, and retinoid metabolism. This model can be used for preclinical studies of novel therapeutic targets.
A mutant methionyl-tRNA synthetase-based toolkit to assess induced-mesenchymal stromal cell secretome in mixed-culture disease models
Authors: Burgess Jeremy D. , Amerna Danilyn , Norton Emily S. , Parsons Tammee M. , Perkerson Ralph B. , Faroqi Ayman H. , Wszolek Zbigniew K. , Guerrero Cazares Hugo , Kanekiyo Takahisa , Delenclos Marion , McLean Pamela J. 
Published: October 2023

Abstract
Background
Mesenchymal stromal cells (MSCs) have a dynamic secretome that plays a critical role in tissue repair and regeneration. However, studying the MSC secretome in mixed-culture disease models remains challenging. This study aimed to develop a mutant methionyl-tRNA synthetase-based toolkit (MetRSL274G) to selectively profile secreted proteins from MSCs in mixed-culture systems and demonstrate its potential for investigating MSC responses to pathological stimulation.

Methods
We used CRISPR/Cas9 homology-directed repair to stably integrate MetRSL274G into cells, enabling the incorporation of the non-canonical amino acid, azidonorleucine (ANL), and facilitating selective protein isolation using click chemistry. MetRSL274G was integrated into both in H4 cells and induced pluripotent stem cells (iPSCs) for a series of proof-of-concept studies. Following iPSC differentiation into induced-MSCs, we validated their identity and co-cultured MetRSL274G-expressing iMSCs with naïve or lipopolysaccharide (LPS)-treated THP-1 cells. We then profiled the iMSC secretome using antibody arrays.

Results
Our results showed successful integration of MetRSL274G into targeted cells, allowing specific isolation of proteins from mixed-culture environments. We also demonstrated that the secretome of MetRSL274G-expressing iMSCs can be differentiated from that of THP-1 cells in co-culture and is altered when co-cultured with LPS-treated THP-1 cells compared to naïve THP-1 cells.

Conclusions
The MetRSL274G-based toolkit we have generated enables selective profiling of the MSC secretome in mixed-culture disease models. This approach has broad applications for examining not only MSC responses to models of pathological conditions, but any other cell type that can be differentiated from iPSCs. This can potentially reveal novel MSC-mediated repair mechanisms and advancing our understanding of tissue regeneration processes.
Stem cell therapy for inherited retinal diseases: a systematic review and meta-analysis
Authors: Chen Xiaodong , Xu Ningda , Li Jiarui , Zhao Mingwei , Huang Lvzhen 
Published: October 2023

Abstract
Purpose
Stem cell therapy is a promising therapeutic approach for inherited retinal diseases (IRDs). This study aims to quantitatively examine the effectiveness and safety of stem cell therapy for patients with IRDs, including retinitis pigmentosa and Stargardt disease (STGD).

Methods
We searched PubMed, EMBASE, Web of Science, Cochrane Library databases, and the ClinicalTrials.gov website. The latest retrieval time was August 20, 2023. The primary outcomes were rates and mean difference (MD) of best-corrected visual acuity (BCVA) improvement. Subgroup analyses were conducted according to administration routes and stem cell types. This study was registered with PROSPERO (CRD42022349271).

Results
Twenty-one prospective studies, involving 496 eyes (404 RP and 92 STGD) of 382 patients (306 RP and 76 STGD), were included in this study. For RP, the rate of BCVA improvement was 49% and 30% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months post-treatment (MD = − 0.12 logMAR, 95% CI .17 to − 0.06 logMAR; P < 0.001), while there was no significant difference at 12 months post-treatment (MD = -0.06 logMAR; 95% CI − 0.13 to 0.01 logMAR; P = 0.10). For STGD, the rate of BCVA improvement was 60% and 55% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months (MD = − 0.14 logMAR, 95% CI − 0.22 to − 0.07 logMAR; P = 0.0002) and 12 months (MD = − 0.17 logMAR, 95% CI − 0.29 to − 0.04 logMAR; P = 0.01). Subgroup analyses showed suprachoroidal space injection of stem cells may be more efficient for RP. Eleven treated-related ocular adverse events from three studies and no related systemic adverse events were reported.

Conclusions
This study suggests stem cell therapy may be effective and safe for patients with RP or STGD. The long-term vision improvement may be limited for RP patients. Suprachoroidal space injection of stem cells may be a promising administration route for RP patients. Limited by the low grade of evidence, large sample size randomized clinical trials are required in the future.