bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing pain in multiple sclerosis: Test–retest reliability of patient-reported outcome measures and accuracy of screening tools
Authors: Yilmazer Cigdem , D’haeseleer Miguel , Soler Bernardita , Van Wijmeersch Bart , Solaro Claudio , Ciampi Ethel , Carcamo Claudia , Van Asch Paul , Cambron Melissa , Lamers Ilse , Feys Peter 
Published: January 2025

Background: Pain is a common symptom of multiple sclerosis (MS). The reliability of outcome measures for pain and the accuracy of screening tools are essential for treatment purposes. Objectives: This study investigated the test–retest reliability of Neuropathic Pain Scale (NPS), Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory-Short Form (BPI-SF), Nordic Musculoskeletal Questionnaire (NMQ), Douleur Neuropathique 4 (DN4), and painDETECT, and the accuracy of DN4 and painDETECT. Methods: 110 persons with MS were included (mean age: 45.35 ± 12.73; Expanded Disability Status Scale (EDSS): 3 (Interquartile range, IQR: 2.6)). The reliability (internal consistency, test–retest, measurement error) and accuracy (area under the curve (AUC), specificity, sensitivity, positive predictive value, and negative predictive value) were analyzed. Results: All included pain assessment tools showed good test–retest reliability (Intraclass correlation coefficient, ICC, (95% confidence interval, CI): 0.85 (0.79–0.89)–0.89 (0.84–0.92)) and good-to-excellent internal consistency (Cronbach’s α: 0.73–0.93). The test–retest reliability of NMQ was moderate to substantial (Cohen’s κ = 0.54–0.87). The overall accuracy of DN4 compared to the neurologist’s diagnosis was acceptable (AUC = 0.762), while that of painDETECT was poor (AUC = 0.682) and demonstrated inadequate predictive ability. Conclusion: All pain outcome measures were reliable in patients with MS (pwMS). DN4 can be used to screen neuropathic pain in MS. Clinical trial registry name: Reliability and Validity of Outcome Measures for Pain in MS https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CRMD&selectaction=Edit&uid=U0006NAA&ts=2&cx=-jzvd6m Registration number: NCT05742152
Real-time ultrasound-guided thoracic epidural placement: Illustrating the techniques and reporting on prospective observational study
Authors: Sutthibenjakul Karuna , Pakpirom Jatuporn , Siripruekpong Sirikarn , Boonchuduang Somrutai 
Published: January 2025

Background: This study aimed to assess the feasibility of real-time ultrasound-guided thoracic epidural placement. Methods: A prospective observational study was conducted in 20 patients undergoing elective abdominal and thoracic surgery. The procedure, performed with patients in a lateral position, involved three sequential steps: (1) identification of the interlaminar gap, (2) advancement of the Touhy needle, and (3) identification of the epidural space. Success was defined as the catheter insertion with achieving sensory blockade. The estimated and actual epidural depth, thoracic epidural placement success rate and procedural time were recorded. Results: The average age and body mass index were 62.1 ± 8.9 years and 22.4 ± 4.4 kg/m2. Thoracic epidural placement was successful in 18 patients (90%, 95% confidence interval: 77–100), and at first attempt in 12 of those (66.7%). The thoracic epidural placement times and total procedural time were 5 (4–6.75) min and 19.5 ± 5.4 min, respectively. The correlation between ultrasound-estimated epidural depth and actual depth was 0.81. Conclusion: Ultrasound guidance enhances thoracic epidural success rates and reduces attempts and skin punctures.
Plain Language Summary of Publication: What is the effect of the medicine vibegron in the treatment of overactive bladder in patients with and without bladder leakage?
Authors: Staskin David , Frankel Jeffrey , Gregg Steven G. , Owens-Grillo Janet 
Published: January 2025

What is this summary about? People with overactive bladder need to use the bathroom many times a day to urinate (pee). This need may often be sudden and may cause some people with overactive bladder to have accidental bladder leakage. The EMPOWUR trial looked at how well a medicine called vibegron worked to help people with overactive bladder. The study also included another drug that was already available for treating overactive bladder called tolterodine and a pill with no medicine called a placebo. Both vibegron and tolterodine were compared with placebo. Participants had improvements in their overactive bladder symptoms after taking either vibegron or tolterodine compared to placebo. The medicine vibegron was approved in 2020 by the US Food and Drug Administration (also called the FDA) to treat overactive bladder. Researchers next wanted to see how well vibegron worked in people from the EMPOWUR trial split into 2 groups. One group was made of participants with overactive bladder who have accidental leakage. The second group was made of participants with overactive bladder who do not have accidental leakage. This is a plain language summary of the study of how well vibegron works for those 2 groups from the EMPOWUR study that was published in the International Journal of Clinical Practice. What were the results? Study participants who took vibegron needed to pee fewer times per day. The number of times they had little warning before the need to pee was also lower. The results were the same for study participants who did and did not have accidental leakage related to overactive bladder. What do the results mean? This study suggests that vibegron can improve symptoms in people with overactive bladder whether or not they have accidental bladder leakage.
Diagnostic utility of lipocalin 2 and metalloproteinase 9 levels in early-stage endometrial cancer
Authors: Ünüvar Songül , Melekoğlu Rauf , Yüce Hande , Çelik Nesibe Zeyveli , Okumuş Ezgi Bulut , Toprak Serhat , Tanbek Kevser , Yaşar Şeyma , Doğan Ayşegül , Türkmen Neşe Başak , Yılmaz Ercan , Sandal Süleyman 
Published: January 2025

Background Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC. Objectıves The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression. Methods A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled. Results There was a significant difference between diagnosis (p < 0.001), surgical procedure (p < 0.001), pathology (p = 0.002), stage (p < 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p < 0.001), and staining intensity (p < 0.001), MMP9 (p = 0.023), LCN2 (p < 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-α) (p = 0.044), menopause duration (p = 0.001), body weight (p < 0.001), and body mass index (BMI) (p < 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies. Conclusıon LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.
Redefining the Approach to Resettlement and Reception: The Humanitarian Corridors Experience in Italy
Authors: Enna Antea 
Published: January 2025

Executive Summary In an era of global uncertainty and multiple humanitarian crises, migration is a matter of life and death for many. In the Mediterranean, the migration drive from Africa and the Middle East has been restricted by European containment policies that have forced asylum seekers and refugees to depend on smugglers and illegal sea-crossing, resulting in numerous tragedies in which many have died. The lack of a secure path to access international protection and safe and legal entry to Europe and the increase in vulnerable people seeking international protection have motivated some stakeholders to outline and test new approaches to support refugees’ resettlement. Humanitarian corridors are a civil society response to support refugees and asylum seekers to reach Europe legally and safely. Although not without its drawbacks, the approach has proved highly effective. This article explores the humanitarian corridors from Lebanon to Italy, delving into the experiences of Syrian refugees who have participated in the program and those who have been involved in its implementation. It examines the weaknesses and strengths of the humanitarian corridors program based on feedback from program beneficiaries, field staff in Lebanon, and those in charge of the reception in Italy. Results reveal that, overall, this approach has proven to be highly effective as the humanitarian corridors are a civil society response to support refugees and asylum seekers to reach Europe legally and safely. Moreover, findings show that expanding humanitarian corridors on a larger scale is possible. The growth of humanitarian corridors depends on the political commitment of member states, the European Union policies and financial allocation, and civil society actors. Collaboration between governments and civil society could boost the potential for expansion, ensuring safe and legal entry for more individuals in need.
D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes
Authors: Luo Jialiang , Wu Tianxing , Zhang Jing , Liang Zhicheng , Shao Weijie , Wang Di , Li Lei , Zuo Daming , Zhou Jia 
Published: January 2025

Abstract

Background
Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.

Methods
Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What’s more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting.

Results
We first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK.

Conclusion
As far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.
getphylo: rapid and automatic generation of multi-locus phylogenetic trees
Authors: Booth T. J. , Shaw S. , Cruz-Morales P. , Weber T. 
Published: January 2025

Abstract

Background
The increasing amount of genomic data calls for tools that can create genome-scale phylogenies quickly and efficiently. Existing tools rely on large reference databases or require lengthy de novo calculations to identify orthologues, meaning that they have long run times and are limited in their taxonomic scope. To address this, we created getphylo, a python tool for the rapid generation of phylogenetic trees de novo from annotated sequences.

Results
We present getphylo (
Ge
nbank
t
o
Phylo
geny), a tool that automatically builds phylogenetic trees from annotated genomes alone. Orthologues are identified heuristically by searching for singletons (single copy genes) across all input genomes and the phylogeny is inferred from a concatenated alignment of all coding sequences by maximum likelihood. We performed a thorough benchmarking of getphylo against two existing tools, autoMLST and GTDB-tk, to show that it can produce trees of comparable quality in a fraction of the time. We also demonstrate the flexibility of getphylo across four case studies including bacterial and eukaryotic genomes, and biosynthetic gene clusters.

Conclusions
getphylo is a quick and reliable tool for the automated generation of genome-scale phylogenetic trees. getphylo can produce phylogenies comparable to other software in a fraction of the time, without the need large local databases or intense computation. getphylo can rapidly identify orthologues from a wide variety of datasets regardless of taxonomic or genomic scope. The usability, speed, flexibility of getphylo makes it a valuable addition to the phylogenetics toolkit.
Gender inequalities in prescribing and initiation patterns of guideline-recommended drugs after acute myocardial infarction
Authors: López-Ferreruela Irene , Malo Sara , Obón-Azuara Blanca , Rabanaque María José , Gamba Adriana , Castel-Feced Sara , Aguilar-Palacio Isabel 
Published: January 2025

Abstract

Background
European guidelines recommend the prescription of certain drugs after acute myocardial infarction (AMI). The existence of gender differences in pharmacological treatment after an AMI has been described. This study aims to describe and analyse, using real-world data (RWD), whether there are gender differences in the prescribing patterns and initiation of treatment in secondary prevention after a first AMI, and which are the factors that explain these differences.

Methods
A population-based observational study of RWD was conducted in the CARhES (CArdiovascular Risk factors for hEalth Services research) cohort. The study included subjects who had experienced a first episode of AMI between 2017 and 2022, had survived the event, and had a minimum follow-up of 180 days.

Results
3,975 subjects were followed 180 days after a first AMI. Women (27.8% of the study population) were older and had more comorbidities. Of the main guideline-recommended drugs, antiplatelets, lipid modifying agents and beta-blockers, were prescribed less often in women. Comedications such as rivaroxaban and calcium channel blockers were more likely to be prescribed in women. The proportion of subjects initiating treatment was similar in both genders.
Overall, age and morbidity burden were the main contributors to differences in the prescribing patterns. Living in an urban area seemed to be a protective or mitigating factor. There were controversial results regarding socioeconomic level.

Conclusion
In our study population, women are older, have greater comorbidities and lower socioeconomic status. Despite this, gender inequalities in the prescribing patterns after a first AMI remains, as women appear to experience less therapeutic effort. It is crucial to analyse them from an intersectional perspective, considering the influence of multiple axes of inequality on health, in order to develop gender-sensitive strategies with a multidisciplinary approach.
Influence of pelvic position on shoulder range of motion
Authors: Lobbos Bishoy S. , Essa Mohamed M. M. , Khaireldin Alaaeldin , Gamal El-Din Mohamed Y. , Rizkallah Phillips , Samy Heba Allah 
Published: January 2025

Abstract

Background
pelvis and shoulder are deeply integrated. They are connected by myofascial slings. The pelvic and spinal posture affects the position of the scapula and the activity of its muscles and affects acromio-humeral distance and so that affects shoulder movement. The aim of the study was to investigate the influence of pelvic position on the shoulder range of motion.

Methods
The full active range of motion (flexion/extension, abduction, and external/internal rotation) of both shoulders was measured by digital goniometer for 33 normal adult subjects. Measurements were taken from a standing position in the following pelvic positions: 1- Neutral posture, 2- Evoked anterior and posterior pelvic tilt, 3- Evoked right and left pelvic rotation, 4- Evoked right and left lateral pelvic tilt. For every shoulder movement, One-Way ANOVA including Tukey post hoc test was used to compare between different positions.

Results
Anterior pelvic tilt leads to a significant increase in flexion and a significant decrease in extension of both shoulders (P value was < 0.001). Posterior pelvic tilt leads to the opposite. Pelvic rotation leads to a significant decrease in shoulder flexion on the same side of rotation and shoulder extension on the opposite side of rotation (P value was < 0.001). Lateral pelvic tilt leads to a significant decrease in abduction on the same side of lateral tilt (P value was < 0.001).

Conclusion
pelvic position affects shoulder range of motion.
Development of Virus-Like Particles (VLPs) for Hepatitis C Virus genotype 4: a novel approach for vaccine development in Egypt
Authors: Ali Ahmed A. , Azouz Rasha A. M. , Hussein Nahla A. , El-Shenawy Reem , Helmy Naiera M. , El-Abd Yasmine S. , Tabll Ashraf A. 
Published: January 2025

Abstract

Background
Egypt has the highest global prevalence of Hepatitis C Virus (HCV) infection, particularly of genotype 4. The development of a prophylactic vaccine remains crucial for HCV eradication, yet no such vaccine currently exists due to the vaccine development challenges. The ability of Virus-Like Particles (VLPs) to mimic the native virus and incorporate neutralizing and conformational epitopes, while effectively engaging both humoral and cellular immune responses, makes them a promising approach to addressing the challenges in HCV vaccine development.

Methods
Lentiviral-based vectors were constructed and employed to integrate the full-length sequence of Core, E1, E2, and P7 genes of HCV genotype 4 into the genome of Human Embryonic Kidney cells (HEK293T). Upon the expression, HCV structural proteins can oligomerize and self-assemble into VLPs mimicking the structure of HCV native virus. VLPs were purified and characterized for the development of a potential VLPs-based vaccine.

Results
In this study, mammalian cells were successfully engineered to stably express HCV structural proteins and generate non-infectious VLPs for HCV genotype 4. The expression of HCV-integrated genes resulted in a successful production of HCV structural proteins, which oligomerized and self-assembled into two layers enveloped VLPs. Electron microscopy analysis of purified VLPs revealed spherical particles with an average diameter of 60–65 nm, closely resembling mature HCV virions. These results highlighted the potential of these VLPs as a vaccine candidate for HCV genotype 4.

Conclusions
HCV genotype 4 remains an underexplored target in vaccine development, despite its significant public health burden, especially in Egypt. The successful generation of VLPs for this genotype represents a promising avenue for further vaccine development. The established system provides a robust platform for the production and study of VLP-based vaccines targeting HCV genotype 4.
Tissue-specific roles of de novo DNA methyltransferases
Authors: Tóth Dániel Márton , Szeri Flóra , Ashaber Mária , Muazu Muhyiddeen , Székvölgyi Lóránt , Arányi Tamás 
Published: January 2025

Abstract
DNA methylation, catalyzed by DNA methyltransferases (DNMT), plays pivotal role in regulating embryonic development, gene expression, adaption to environmental stress, and maintaining genome integrity. DNMT family consists of DNMT1, DNMT3A, DNMT3B, and the enzymatically inactive DNMT3L. DNMT3A and DNMT3B establish novel methylation patterns maintained by DNMT1 during replication. Genetic variants of DNMT3A and DNMT3B cause rare diseases such as Tatton-Brown-Rahman and ICF syndromes. Additionally, somatic mutations cause common conditions such as osteoarthritis, osteoporosis, clonal hematopoiesis of indeterminate potential (CHIP), hematologic malignancies, and cancer. While DNMTs have been extensively studied in vitro, in early development and in disease, their detailed physiologic roles remain less understood as in vivo investigations are hindered by the embryonic or perinatal lethality of the knockout mice. To circumvent this problem, tissue-specific Dnmt3a and Dnmt3b knockouts were engineered. This review explores their diverse molecular roles across various organs and cell types and characterizes the phenotype of the knockout mice. We provide a comprehensive collection of over forty tissue-specific knockout models generated by cre recombinase. We highlight the distinct functions of DNMT3A and DNMT3B in germ cells, early development, uterus, hematopoietic differentiation, musculoskeletal development, visceral organs, and nervous system. Our findings indicate that DNMT3A primarily regulates hematopoietic differentiation, while DNMT3B is crucial for cartilage homeostasis and ossification. We emphasize the context-dependent roles of DNMT3A and DNMT3B and demonstrate that they also complement DNMT1 maintenance methyltransferase activity. Overall, the expression patterns of DNMTs across tissues provide insights into potential therapeutic applications for treating neurologic diseases, cancer, and osteoporosis.
Central venous pressure as a method of optimising atrio-ventricular delay after cardiac surgery
Authors: Tindale Alexander , Cretu Ioana , Gomez Naomi , Haynes Ross , Meng Hongying , Mason Mark J. , Francis Darrel P. 
Published: January 2025

Introduction
Haemodynamic atrioventricular delay (AVD) optimisation has primarily focussed on signals that are not easy to acquire from a pacing system itself, such as invasive left ventricular catheterisation or arterial blood pressure (ABP). In this study, standard clinical central venous pressure (CVP) signals are tested as a potential alternative.

Methods
Sixteen patients with a temporary pacemaker after cardiac surgery were studied. AV delay optimisation was performed by alternating between a reference AVD of 120ms and tested settings ranging from 40 to 280ms, with 8 replicates for each setting. Alongside (a) the raw data, three methods of correcting for respiration were tested: (b) limiting analysis to a respiratory cycle, (c) asymmetric least squares (ALS) and (d) discrete wavelet transform (DWT). The utility of a quality control step was tested.

Results
CVP signals were a mirror image of the systolic ABP signals: The four R values were -0.674, -0.692, -0.631, -0.671 respectively (all p<0.001). With quality control, the mirror image was best for DWT (R = -0.76, p<0.001), with the CVP and ABP optima agreeing well (R = 0.78, p<0.001). The automated quality control signal correctly predicted the gap between the AVD optima calculated from ABP and CVP (R = 0.8, p<0.001).

Conclusions
Central venous pressure signals could be used to optimise AVD, because they have a reliable inverse relationship with ABP when pacemaker settings undergo protocolised testing. However, protocols need careful design to circumvent spontaneous biological variability.