bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer
Authors: Navarro-Domenech Inmaculada , Arulanantham Shinthujah , Liu Zhihui Amy , Tjong Michael , Kong Vickie , Malkov Victor , Tadic Tony , Fleshner Neil , Kulkarni Girish , Zlotta Alexandre R , Catton Charles , Berlin Alejandro , Sridhar Srikala , Jiang Di , Chung Peter , Raman Srinivas 
Published: September 2023

Abstract
Purpose/Objective
Definitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT.

Material/Methods
This was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS.

Results
117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5–89.2) and 46% (95% CI 36.5–57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%.

Conclusion
Partial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.
Type III NRG-1 plays a regulatory role in the regeneration process of nerves from the beginning of transplantation
Authors: Wang Jun-Ning , He Sai , Yang Wei-xia , Lu Yao , Li Kun , Zhang Yu-Min , Wang Ya-Kang 
Published: September 2023

AbstractThe present study investigated the effect of type III Neuregulin-1 (NRG-1) on changes in the myelin sheath and the recovery of nerve function during the regeneration process following autologous nerve transplantation. Seventy-two Sprague–Dawley rats were divided into a Blank, Model and (antisense oligonucleotide, ASON) group. The Model and ASON groups of SD rats were subjected to autologous nerve transplantation, and the Blank group only had the sciatic nerve exposed. The Model and ASON groups were given local injections of 2 ml PBS buffer solution and 2 ml ASON of Type III NRG-1, respectively, the NRG-1 type III was inhibited by ASON. Changes in the sciatic nerve functional index (SFI) and conduction velocities were observed at different 6 time points. Regeneration of the myelin sheath was observed using transmission electron microscopy. Type III NRG-1 protein was detected using Western blotting and immunohistochemistry, and NRG-1 mRNA was detected using PCR. The SFI of the ASON group was lower than the Model group after transplantation. The conduction velocities of the ASON group on the 14th and 21st days after autologous nerve transplantation were lower than the Model group (P < 0.01). The protein and mRNA expression of type III NRG-1 in the ASON group was lower than the Model group at all 6 time points. The area of medullated nerve fibres was significantly different between the ASON group and the Model group on the 3rd day (P < 0.05), as was the number of medullated nerve fibres per unit area (P < 0.01). The diameter of axons was obviously different between the two groups (P < 0.01). Type III NRG-1 played an important regulatory role in the regeneration process of the nerve from the beginning of transplantation to the 28th day.
Shuangshen Ningxin capsule alleviates myocardial ischemia–reperfusion injury in miniature pigs by modulating mitophagy: network pharmacology and experiments in vivo
Authors: Jia Feifan , Chen Yuanyuan , Xin Gaojie , Li Lingmei , Liu Zixin , Xu Sujuan , Gao Jiaming , Meng Hongxu , Shi Yue , Ma Yanlei , Li Lei , Fu Jianhua 
Published: September 2023

Abstract
Background
Myocardial ischemia/reperfusion injury (MI/RI) is involved in a variety of pathological states for which there is no effective treatment exists. Shuangshen Ningxin (SSNX) capsule which is developed by Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine has been demonstrated to alleviate MI/RI, but its mechanism remains to be further elucidated.

Methods
The MI/RI miniature pigs model was constructed to assess the pharmacodynamics of SSNX by blocking the proximal blood flow of the left anterior descending branch of the cardiac coronary artery through an interventional balloon. The principal chemical compounds and potential targets of SSNX were screened by HPLC–MS and SwissTargetPrediction. The targets of MI/RI were identified based on Online Mendelian Inheritance in Man (OMIM) and GeneCards. Cytoscape 3.9.0 was applied to construct a protein–protein interaction (PPI) network, and Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using metascape. To further validate the mechanism of SSNX, Molecular docking, Transmission electron microscopy, and Western blot analysis were used to test the effectiveness of targets in related pathways.

Results
Our results indicated that SSNX significantly improved cardiac function, attenuated myocardial I/R injury. Through network analysis, a total of 15 active components and 201 targets were obtained from SSNX, 75 of which are potential targets for the treatment of MI/RI. KEGG and MCODE analysis showed that SSNX is involved in the mitophagy signaling pathway, and ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rb2 are key components associated with the mitophagy. Further experimental results proved that SSNX protected mitochondrial structure and function, and significantly reduced the expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1), Parkin, FUN14 domain containing 1 (FUNDC1) and Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) in MI/RI miniature pigs.

Conclusion
In our study, the integration of network pharmacology and experiments in vivo demonstrated that SSNX interfered with MI/RI by inhibiting mitophagy.
Age-related hearing loss and its potential drug candidates: a systematic review
Authors: Hu Shiyu , Sun Qingru , Xu Fei , Jiang Ninghua , Gao Jianli 
Published: September 2023

Abstract
Background
Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials.

Objectives
The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL.

Methods
Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis.

Results
Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects.

Conclusion
Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K+ channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.
CRISPR/Cas9-mediated activation of NR5A1 steers female human embryonic stem cell-derived bipotential gonadal-like cells towards a steroidogenic cell fate
Authors: Danti Laura , Lundin Karolina , Sepponen Kirsi , Yohannes Dawit A. , Kere Juha , Tuuri Timo , Tapanainen Juha S. 
Published: September 2023

AbstractThe nuclear receptor subfamily 5 group A member 1 (NR5A1), encoding steroidogenic factor 1 (SF-1), has been identified as a critical factor in gonadal development in animal studies. A previous study of ours suggested that upregulation of NR5A1 during early gonadal differentiation in male (46,XY) human pluripotent stem cells steers the cells into a more mature gonadal cell type. However, the detailed role of NR5A1 in female gonadal differentiation has yet to be determined. In this study, by combining the processes of gonadal differentiation and conditional gene activation, we show that NR5A1 induction predominantly upregulates the female gonadal marker inhibin subunit α (INHA) and steroidogenic markers steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 17 subfamily A member 1 (CYP17A1), hydroxy-delta-5-steroid dehydrogenase (HSD3B2) and hydroxysteroid 17-beta dehydrogenase 1 (HSD17B1). In contrast, NR5A1 induction did not seem to affect the bipotential gonadal markers gata binding protein 4 (GATA4) and Wilms’ tumour suppressor 1 (WT1) nor the female gonadal markers r-spondin 1 (RSPO1) and wnt family member 4 (WNT4). Differentially expressed genes were highly associated with adrenal and ovarian steroidogenesis pathways. Moreover, time-series analysis revealed different dynamic changes between male and female induced samples, where continuously upregulated genes in female gonadal differentiation were mostly associated with adrenal steroidogenesis. Thus, in contrast to male gonadal differentiation, NR5A1 is necessary but not sufficient to steer human embryonic stem cell (hESC)-derived bipotential gonadal-like cells towards a more mature somatic, female cell fate. Instead, it seems to direct bipotential gonadal-like cells more towards a steroidogenic-like cell population. The information obtained in this study helps in elucidating the role of NR5A1 in gonadal differentiation of a female stem cell line.
Whole-genome characterization of common rotavirus strains circulating in Vellore, India from 2002 to 2017: emergence of non-classical genomic constellations
Authors: Khakha Shainey Alokit , Varghese Tintu , Giri Sidhartha , Durbin Alan , Tan Gene S. , Kalaivanan Maheswari , Prasad Jasmin Helan , Kang Gagandeep 
Published: September 2023

AbstractRotaviruses (RVs) are the most common etiological agent of acute gastroenteritis among young children, even after vaccine introduction in low-income countries. A whole-genome classification representing the 11 RV genes, was introduced for surveillance and characterization of RVs. This study characterized the common circulating strains in Vellore, India from 2002 to 2017 to understand rotavirus strain diversity and evolution using Whole genome sequencing (WGS) carried out on Illumina MiSeq. The 89% (92% of Wa-like, 86% of DS-1-like) of strains had classical constellations, while reassortant constellations were seen in 11% (8% of Wa-like, 14% of DS-1-like) of the strains. The rare E6-NSP4 in combination with DS-1 like G1P[8] and the emergence of the OP-354 subtype of P[8] were identified. Phylogenetics of RV strains revealed multiple subtypes circulating in the past 15 years, with strong evidence of animal to human gene transmission among several strains.
Splenic sarcoid reaction mimicking metastases in patients after uterine cancer surgery: a report of two cases
Authors: Kitamura Kei , Ogura Toshiro , Miyamoto Ryoichi , Ishida Hiroyuki , Matsudaira Shinichi , Takahashi Amane , Kanda Hiroaki , Fukuda Takashi 
Published: September 2023

Abstract
Background
Tumor-associated sarcoid reactions have been observed with various tumors; however, they have not been reported with uterine cancer. We present two cases of splenic sarcoid reactions that mimicked metastases a few years after uterine cancer surgery.

Case presentation
Case 1 involved a 67-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent open total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Three years after the initial surgery, computed tomography (CT) and positron emission tomography CT showed multiple splenic masses with increasing numbers and sizes. Splenic metastases were diagnosed, and laparoscopic splenectomy was performed. The histopathological analysis revealed sarcoid reactions in the spleen. Case 2 involved a 47-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Two years after the initial surgery, multiple splenic masses were observed. We performed laparoscopic splenectomy for the splenic metastases. Granuloma formations were identified in the splenic specimen and perisplenic lymph nodes that were removed simultaneously, resulting in a final diagnosis of sarcoid reaction. A review of the lymph nodes at the time of the previous uterine surgery revealed granuloma formation. Other than the presence of splenic masses, no findings suggestive of recurrence were observed in these cases. Uterine cancer and sarcoid reactions progressed without recurrence after splenectomy.

Conclusions
To the best of our knowledge, this is the first report of the late development of splenic sarcoid reactions after uterine cancer surgery. Sarcoid reactions and metastases are difficult to diagnose based on preoperative imaging results. However, reviewing the specimen at the time of the initial resection, the number of lesions, and the clinical findings (other than imaging findings) may aid in the determination of the correct diagnosis.
Thiothrix and Sulfurovum genera dominate bacterial mats in Slovak cold sulfur springs
Authors: Nosalova Lea , Mekadim Chahrazed , Mrazek Jakub , Pristas Peter 
Published: September 2023

AbstractMicrobiota of sulfur-rich environments has been extensively studied due to the biotechnological potential of sulfur bacteria, or as a model of ancient life. Cold terrestrial sulfur springs are less studied compared to sulfur-oxidizing microbiota of hydrothermal vents, volcanic environments, or soda lakes. Despite that, several studies suggested that sulfur springs harbor diverse microbial communities because of the unique geochemical conditions of upwelling waters. In this study, the microbiota of five terrestrial sulfur springs was examined using a 16 S rRNA gene sequencing. The clear dominance of the Proteobacteria and Campylobacterota phyla of cold sulfur springs microbiota was observed. Contrary to that, the microbiota of the hot sulfur spring was dominated by the Aquificota and Firmicutes phylum respectively. Sulfur-oxidizing genera constituted a dominant part of the microbial populations with the Thiothrix and Sulfurovum genera identified as the core microbiota of cold sulfur terrestrial springs in Slovakia. Additionally, the study emphasizes that sulfur springs in Slovakia support unique, poorly characterized bacterial communities of sulfur-oxidizing bacteria.
The “World Migration Congress” of 1926 and the Limits of Socialist Internationalism
Authors: Poy Lucas 
Published: September 2023

AbstractIn recent years, scholars doing research on the anticommunist and social democratic tradition developed an interpretation in which socialist internationalism is portrayed not as opposed to nationalism but instead as complementary. This allowed them to move away from older perspectives and to examine the main features of international cooperation among socialists in a more positive light. Its substantial and convincing contributions notwithstanding, this literature also displays important shortcomings. Not only does it minimize the challenge that nationalism did pose to transnational solidarities; it is also too focused on Europe and therefore overlooks a more serious limit to internationalism, namely a perspective that proclaimed a principle of color-blind solidarity among all peoples of the world but in practice built a much more limited transnational community of workers either born in Europe or of European descent. This article engages with these historiographical trends and complicates our knowledge of socialist internationalism in the 1920s by exploring a unique and underresearched event, the “World Migration Congress,” held in London in 1926 and jointly organized by the International Federation of Trade Unions and the Labour and Socialist International, the main transnational networks of trade unionists and political parties of the social democratic tradition. Drawing on the idea that international organizations and meetings can be used as “observation points” for studying global history, the article uses the prolegomena to, the preparations for, and the discussions of this congress as a lens to understand the stances of socialist parties and reformist trade unions regarding the question of migration in the 1920s, explaining to what extent, and for what reason, they have changed in comparison with the prewar period. Moreover, it shows that the stances on migration were intertwined in many ways with socialist and labor perspectives on colonialism and condescending views of the “colored peoples” of the world.
Changes in Desk-Based Workers’ Sitting, Standing, and Stepping Time: Short- and Longer-Term Effects on Musculoskeletal Pain
Authors: DZAKPASU FRANCIS Q. S. , OWEN NEVILLE , CARVER ALISON , BRAKENRIDGE CHRISTIAN J. , EAKIN ELIZABETH G. , HEALY GENEVIEVE N. , LAMONTAGNE ANTHONY D. , MOODIE MARJ , COENEN PIETER , STRAKER LEON , DUNSTAN DAVID W. 
Published: September 2023

ABSTRACT

Purpose
Sitting at work can be associated with musculoskeletal pain, but the effect of reductions in sitting is not well understood. We examined relationships with musculoskeletal pain of changes in sitting, standing, stepping, and short and long bouts of these behaviors.

Methods
Analyses pooled data from 224 desk workers (68.4% women; mean ± SD age = 45.5 ± 9.4 yr; body mass index = 28.1 ± 6.1 kg⋅m−2) in intervention trial. Device-assessed (activPAL3) sitting, standing, and stepping time and multisite musculoskeletal pain (Nordic Questionnaire; 12 body areas) were assessed at baseline, 3 months, and 12 months. Compositional data analyses in linear mixed-effects regressions examined relationships within 16 waking hours of the behaviors and their short and long bouts, with changes from baseline in acute and chronic multisite musculoskeletal pain at 3 and 12 months. Analyses were adjusted for initial group randomization and relevant covariates.

Results
At 3 months, increased standing relative to changes in other compositions was significantly associated with increased multisite musculoskeletal pain (acute: β = 1.54, 95% confidence interval [CI] = 0.10 to 2.98; chronic: β = 1.49, 95% CI = 0.12 to 2.83). By contrast, increased stepping relative to changes in other compositions was significantly associated with reduced multisite musculoskeletal pain (acute: β = −1.49, 95% CI = −2.97 to −0.02; chronic: β = −1.87, 95% CI = −3.75 to −0.01). Neither sitting reduction relative to changes in other compositions nor changes in short bouts relative to long bouts of the behaviors were significantly associated with multisite musculoskeletal pain changes. At 12 months, there were no significant associations for any of the compositional changes.

Conclusions
In the short term, while increasing standing with reduced sitting time can be unfavorable, concurrently increasing stepping could potentially reduce musculoskeletal pain. In the longer term, musculoskeletal pain may not be increased by moderate reductions in sitting time through spending more time standing or stepping.
Effect of Active Release Technique and Cyriax approach on pain, grip strength and functional performance in individuals with lateral epicondylitis: a randomized clinical trial protocol
Authors: Nagore Aditi N. , Samal Subrat 
Published: September 2023

Background: Tennis elbow, also known as lateral epicondylitis, is a painful condition characterized by irritation of the tendons that link the forearm muscles on the outside of the elbow, which can result from using the elbow too much. Active Release Technique (ART) is defined as a hands-on approach that manages cases to enable the identification and treatment of soft tissue injuries. Through the removal of fibrosis and adhesions that can develop in tissues as a result of overload from frequent use, the aim of ART, a soft tissue treatment, is to lessen tissue stress. Deep transverse friction (DTF) and Mill's manipulation, which are used shortly after DTF, have been used by Cyriax and Cyriax to successfully treat tennis elbow. ART and Cyriax techniques have shown promise for lateral epicondylitis sufferers. There hasn't yet been any research comparing these two approaches for participants with lateral epicondylitis. The aim is to examine the efficiency of ART with the Cyriax technique on lateral epicondylitis pain, strength, and function. Methods: A total number of 60 participants will be included as per the inclusion criteria and then they will be further divided into 30 in each group. The physiotherapy intervention will be given to Groups A (ART) and Group B (Cyriax technique) along with conventional 12 sessions spread across four weeks, three times per week. Each patient will be evaluated during and after treatment on the baseline and after four weeks using the Visual Analogue Scale (VAS), hand grip strength dynamometer, and Patient-rated Tennis Elbow Evaluation (PRTEE) scale. Conclusions: This physiotherapy intervention could be used in the treatment of lateral epicondylitis if our study's hypothesis is found to be accurate. Registration: CTRI (CTRI/2023/06/053660; 08/06/2023).