bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial
Authors: Wu Xin , Yu Hailin , Bai Yongrui , Hou Yanli , Lou Weihua , Wang Xipeng , Zhu Tao , Zhang Yuyang , Hu Weiguo , Xue Xiaohong , Zhu Zhiling , Xiang Libing , Li Jiarui , Fang Xuhong , Gao Shujun , Feng Hua , Diao Wenjing , Zhang Hongwei , Du Ming , Yan Weili , Qiu Ling , Feng Hao , Zhu Shurong , Du Yan , Jiang Hua 
Published: August 2023

Abstract
Background
Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial.

Methods/design
This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements.

Discussion
The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method.

Trial registration
ClinicalTrials.gov, NCT04939831, retrospectively registered on 25 June 2021.
Iguratimod attenuated fibrosis in systemic sclerosis via targeting early growth response 1 expression
Authors: Shen Lichong , Yin Hanlin , Sun Li , Zhang Zhiliang , Jin Yuyang , Cao Shan , Fu Qiong , Fan Chaofan , Bao Chunde , Lu Liangjing , Zhan Yifan , Xu Xiaojiang , Chen Xiaoxiang , Yan Qingran 
Published: August 2023

Abstract
Background
The early growth response 1 (EGR1) is a central transcription factor involved in systemic sclerosis (SSc) pathogenesis. Iguratimod is a synthesized anti-rheumatic disease-modifying drug, which shows drastic inhibition to EGR1 expression in B cells. This study is aiming to investigate the anti-fibrotic effect of iguratimod in SSc.

Methods
EGR1 was detected by immunofluorescence staining real-time PCR or western blot. Iguratimod was applied in EGR1 overexpressed or knockdown human dermal fibroblast, bleomycin pre-treated mice, tight skin 1 mice, and SSc skin xenografts. RNA sequencing was performed in cultured fibroblast and xenografts to identify the iguratimod regulated genes.

Results
EGR1 overexpressed predominantly in non-immune cells of SSc patients. Iguratimod reduced EGR1 expression in fibroblasts and neutralized changes of EGR1 response genes regulated by TGFβ. The extracellular matrix (ECM) production and activation of fibroblasts were attenuated by iguratimod while EGR1 overexpression reversed this effect of iguratimod. Iguratimod ameliorated the skin fibrosis induced by bleomycin and hypodermal fibrosis in TSK-1 mice. Decreasing in the collagen content as well as the density of EGR1 or TGFβ positive fibroblasts of skin xenografts from naïve SSc patients was observed after local treatment of iguratimod.

Conclusion
Targeting EGR1 expression is a probable underlying mechanism for the anti-fibrotic effect of iguratimod.
Transposable elements as essential elements in the control of gene expression
Authors: Gebrie Alemu 
Published: August 2023

AbstractInterspersed repetitions called transposable elements (TEs), commonly referred to as mobile elements, make up a significant portion of the genomes of higher animals. TEs contribute in controlling the expression of genes locally and even far away at the transcriptional and post-transcriptional levels, which is one of their significant functional effects on gene function and genome evolution. There are different mechanisms through which TEs control the expression of genes. First, TEs offer cis-regulatory regions in the genome with their inherent regulatory features for their own expression, making them potential factors for controlling the expression of the host genes. Promoter and enhancer elements contain cis-regulatory sites generated from TE, which function as binding sites for a variety of trans-acting factors. Second, a significant portion of miRNAs and long non-coding RNAs (lncRNAs) have been shown to have TEs that encode for regulatory RNAs, revealing the TE origin of these RNAs. Furthermore, it was shown that TE sequences are essential for these RNAs' regulatory actions, which include binding to the target mRNA. By being a member of cis-regulatory and regulatory RNA sequences, TEs therefore play essential regulatory roles. Additionally, it has been suggested that TE-derived regulatory RNAs and cis-regulatory regions both contribute to the evolutionary novelty of gene regulation. Additionally, these regulatory systems arising from TE frequently have tissue-specific functions. The objective of this review is to discuss TE-mediated gene regulation, with a particular emphasis on the processes, contributions of various TE types, differential roles of various tissue types, based mostly on recent studies on humans.
Students’ COVID-19 vaccine behaviors, intentions, and beliefs at a US Native American-Serving Nontribal Institution (NASNTI)
Authors: Dutta Tapati , Agley Jon , Xiao Yunyu , Golzarri-Arroyo Lilian , Ali Sumayyah 
Published: August 2023

Abstract
Objective
Multiple national and international studies of college student COVID-19 vaccination have been recently published, providing important descriptive information and a conceptual basis to inform future decisions about infectious disease prevention in higher education settings. Yet almost no research has examined Native American-Serving Nontribal Institutions (NASNTIs), which occupy a unique space in US higher education in terms of structure and students served. To address that gap, this report describes results from a two-wave cross-sectional survey administered at a NASNTI in Durango, Colorado, as part of a larger study of COVID-19 campus response. Surveys were administered prior to (wave one) and following (wave two) statewide availability of the COVID-19 vaccine for ages 16+. Comparisons between waves used Cramer’s V and Mann-Whitney U tests.

Results
A total of 283 students responded to wave one, and 186 responded to wave two. Notable results included a self-reported COVID-19 vaccination rate (40.1%) at wave one that far exceeded parallel national rates. Injunctive and disjunctive normative beliefs were also less supportive of vaccination among the unvaccinated at wave two compared to wave one. Findings from this study should be considered in the context of all available evidence and not used to make inferences in isolation.
Feasibility and therapeutical potential of local intracerebral encapsulated cell biodelivery of BDNF to AppNL−G−F knock-in Alzheimer mice
Authors: Tambaro Simone , Mitra Sumonto , Gera Ruchi , Linderoth Bengt , Wahlberg Lars U. , Darreh-Shori Taher , Behbahani Homira , Nilsson Per , Eriksdotter Maria 
Published: August 2023

Abstract
Background
Alzheimer’s disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis. BDNF has been proposed as a potential therapy for AD, but BDNF has low brain penetration. In this study, we used an innovative encapsulated cell biodelivery (ECB) device, containing genetically modified cells capable of releasing BDNF and characterized its feasibility and therapeutic effects in the novel App knock-in AD mouse model (AppNL−G−F).

Methods
ECB’s containing human ARPE-19 cells genetically modified to release BDNF (ECB-BDNF devices) were stereotactically implanted bilaterally into hippocampus of 3-month-old AppNL−G−F mice. The stability of BDNF release and its effect on AD pathology were evaluated after 1, 2-, and 4-months post-implantation by immunohistochemical and biochemical analyses. Exploratory and memory performance using elevated plus maze (EPM) and Y-maze test were performed in the 4-months treatment group. Immunological reaction towards ECB-BDNF devices were studied under ex vivo and in vivo settings.

Results
The surgery and the ECB-BDNF implants were well tolerated without any signs of unwanted side effects or weight loss. ECB-BDNF devices did not induce host-mediated immune response under ex vivo set-up but showed reduced immune cell attachment when explanted 4-months post-implantation. Elevated BDNF staining around ECB-BDNF device proximity was detected after 1, 2, and 4 months treatment, but the retrieved devices showed variable BDNF release. A reduction of amyloid-β (Aβ) plaque deposition was observed around ECB-BDNF device proximity after 2-months of BDNF delivery.

Conclusions
The result of this study supports the use of ECB device as a promising drug-delivery approach to locally administer BBB-impermeable factors for treating neurodegenerative conditions like AD. Optimization of the mouse-sized devices to reduce variability of BDNF release is needed to employ the ECB platform in future pre-clinical research and therapy development studies.
A uterine fibroid presenting as an incarcerated epigastric hernia: a case report and review of the literature
Authors: Atri Souhaib , Hammami Mahdi , Ben Brahim Meriem , Maghrebi Houcine , Kacem Montassar 
Published: August 2023

Abstract
Background
Uterine fibroids incarcerated in abdominal wall hernias during pregnancy are rare, with only six cases reported in umbilical hernias. This case report presents the first reported case of an incarcerated uterine fibroid in an epigastric hernia.

Case presentation
A 31-year-old primigravid Caucasian woman at 28 weeks gestational age presented with sudden onset abdominal pain and vomiting. Physical examination revealed an incarcerated epigastric hernia containing a non-reducible firm mass. Ultrasound showed a healthy fetus, and during surgery, a subserosal and sessile fibroid originating from the anterior uterine wall was found in the hernia sac. It was easily reduced, and the hernia was repaired with no complications. The patient proceeded to deliver a healthy baby boy by cesarean section at full term.

Conclusion
Uterine fibroids incarcerated in abdominal wall hernias during pregnancy are rare and affect mostly primigravid women in the third trimester. Abdominal ultrasound may facilitate the diagnosis, and pedunculated fibroids may be resected while sessile fibroids should be simply reduced. Clinicians should consider incarcerated fibroid as a differential diagnosis in pregnant women with irreducible ventral abdominal wall hernias. This case report aims to contribute to the literature and optimize the management of abdominal wall hernias in pregnant women.
l-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway
Authors: Ma Chunhua , Liao Kexi , Wang Jing , Li Tao , Liu Liangming 
Published: August 2023

Abstract
Backgrounds
Chronic obstructive pulmonary disease (COPD) is a frequent and common disease in clinical respiratory medicine and its mechanism is unclear. The purpose of this study was to find the new biomarkers of COPD and elucidate its role in the pathogenesis of COPD. Analysis of metabolites in plasma of COPD patients were performed by ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (TOF–MS). The differential metabolites were analyzed and identified by multivariate analysis between COPD patients and healthy people. The role and mechanisms of the differential biomarkers in COPD were verified with COPD rats, arginosuccinate synthetase 1 (ASS-l) KO mice and bronchial epithelial cells (BECs). Meanwhile, whether the differential biomarkers can be the potential treatment targets for COPD was also investigated. 85 differentials metabolites were identified between COPD patients and healthy people by metabonomic.

Results
l-Arginine (LA) was the most obvious differential metabolite among the 85 metabolites. Compare with healthy people, the level of LA was markedly decreased in serum of COPD patients. It was found that LA had protective effects on COPD with in vivo and in vitro experiments. Silencing Ass-1, which regulates LA metabolism, and α-methy-dl-aspartic (NHLA), an Ass-1 inhibitor, canceled the protective effect of LA on COPD. The mechanism of LA in COPD was related to the inhibition of ROS/NLRP3/NF-κB signaling pathway. It was also found that exogenous LA significantly improved COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. l-Arginine (LA) as a key metabolic marker is identified in COPD patients and has a protective effect on COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.

Conclusion
LA may be a novel target for the treatment of COPD and also a potential substitute for treating COPD.
Aftershock study of the 2019 Ambon earthquake using moment tensor inversion: identification of fault reactivation in northern Banda, Indonesia
Authors: Baskara Aria W. , Sahara David P. , Nugraha Andri D. , Rusdin Andi Azhar , Zulfakriza Z. , Widiyantoro Sri , Triyoso Wahyu , Priyono Awali , Puspito Nanang T. , Shiddiqi Hasbi Ash , Kusumawati Dian , Rudyawan Alfend , Elly Erfin 
Published: August 2023

AbstractOn September 26, 2019, an Mw 6.5 earthquake occurred 23 km northeast of Ambon City, Indonesia, followed by numerous aftershock series related to a complex fault network reactivation in the Ambon and Seram region. Using moment tensor inversion, we identify the kinematics of fault reactivation based on the focal mechanism solution of 20 aftershocks with Mw > 3.2 and analyze the earthquake sequence from both focal mechanism solutions and spatiotemporal seismicity. The MTs solution of aftershocks revealed three different characteristics of fault reactivation: (i) a 35 km long N-S oriented main fault characterized by dextral strike-slip (ii) a NE-SW reverse fault segment with a ~ 55° northeastward dip located in southwest Seram, and (iii) two strike-slip segments (NNW-SSE and NNE-SSW trends) and an E-W normal fault in Ambon Island. Analysis of spatiotemporal seismicity with the MTs solution suggests that the Mw 6.5 Ambon aftershock sequences can be described as follows: (i) an Mw 6.5 mainshock rupture that was primarily made up of a major strike-slip component and an insignificant minor normal fault; (ii) first aftershock cluster propagate along the main N-S ruptures, followed by the strike-slip and normal cluster in Ambon Island (iii) The reverse fault events cluster appeared next in Southwest Seram. The presence of complex strike-slip segments in Ambon agrees with the regional structure trends in Halmahera, located in the north of the study area, while the E-W oriented normal fault might be related to the eastward velocity increase in Banda Arc, which causes extensional deformation. Given that the fault reactivation identified in Ambon and Seram is located close to the densely populated urban regions of Ambon City and Kairatu, the analysis of future seismic hazards related to this fault reactivation should consider the risks in a region with complex fault settings.
Graphical Abstract
The Japa syndrome and the migration of Nigerians to the United Kingdom: an empirical analysis
Authors: Okunade Samuel Kehinde , Awosusi Oladotun E. 
Published: August 2023

AbstractSince the early years of independence, Africa has witnessed varying degrees of migration-regular and irregular. Scholarships in African regional studies have mainly attributed this phenomenon to factors such as high poverty levels, rising unemployment, and the deplorable economies of most African countries, Nigeria inclusive. However, the post-Covid-19 trend of out-migration of Nigerians to the UK, known as japa to the United Kingdom (UK) and other parts of the world, is concerning with multifaced implications. The study investigates the endogamous and exogamous variables responsible for this Japa syndrome in Nigeria. It contends that beyond the unfavourable economic climate and the lingering security issues among other internal vices in Nigeria, the current trend of out-migration bears a connection with the neo-liberal structure of the UK and the emerging global trend. The study argues further that the mad rush out-migration portends hydra-headed implications for the two countries and Africa at large. The study adopts a qualitative research design, including the utilisation of primary and secondary data. It draws primary data through pre-set standard e-interviews with thirty-six (36) Nigerian University students from seventeen (17) universities in the UK. The thematic analytic framework is applied to this data, with the product being an essay defined by seven sections.
Integrating simulation into surgical training: a qualitative case study of a national programme
Authors: Shah Adarsh P. , Cleland Jennifer , Hawick Lorraine , Walker Kim A. , Walker Kenneth G. 
Published: August 2023

Abstract
Background
Applying simulation-based education (SBE) into surgical curricula is challenging and exacerbated by the absence of guidance on implementation processes. Empirical studies evaluating implementation of SBE interventions focus primarily on outcomes. However, understanding the processes involved in organising, planning, and delivering SBE adds knowledge on how best to develop, implement, and sustain surgical SBE. This study used a reform of early years surgical training to explore the implementation of a new SBE programme in Scotland. It aimed to understand the processes that are involved in the relative success (or failure) when implementing surgical SBE interventions.

Methods
This qualitative case study, underpinned by social constructionism, used publicly available documents and the relevant surgical SBE literature to inform the research focus and contextualise data obtained from semi-structured interviews with core surgical trainees (n = 46), consultant surgeons (n = 25), and key leaders with roles in surgical training governance in Scotland (n = 7). Initial data coding and analysis were inductive. Secondary data analysis was then undertaken using Normalisation Process Theory (NPT). NPTs’ four constructs (coherence, cognitive participation, collective action, reflexive monitoring) provided an explanatory framework for scrutinising how interventions are implemented, embedded, and integrated into practice, i.e. the “normalisation” process.

Results
Distributed leadership (individual SBE initiatives assigned to faculty but overall programme overseen by a single leader) and the quality improvement practise of iterative refinement were identified as key novel processes promoting successful normalisation of the new SBE programme. Other processes widely described in the literature were also identified: stakeholder collaboration, personal contacts/relational processes, effective communication, faculty development, effective leadership, and tight programme management. The study also identified that learners valued SBE activities in group- or team-based social environments over isolated deliberate practice.

Conclusions
SBE is most effective when designed as a comprehensive programme aligned to the curriculum. Programmes incorporating both group-based and isolated SBE activities promote deliberate practice. Distributed leadership amongst faculty attracts wide engagement integral to SBE programme implementation, while iterative programme refinement through regular evaluation and action on feedback encourages integration into practice. The knowledge contributed by critically analysing SBE programme implementation processes can support development of much needed guidance in this area.
New Resinogalea species from Araucaria araucana resin in Chile and reclassification of the genus in the Cryptocaliciomycetidae
Authors: Balocchi Felipe , Barnes Irene , Wingfield Michael J. , Ahumada Rodrigo , Visagie Cobus M. 
Published: August 2023

AbstractAraucaria araucana is an ancient conifer, native to the mountain ranges in Chile and Argentina. These trees host a large number of organisms, mainly insects, strongly or even exclusively associated with them. The recent emergence of a novel canker disease on A. araucana has emphasised the importance of fungi associated with these iconic trees and has resulted in the discovery of various new species. In this study, we considered the identity of an unknown calicioid fungus consistently found on resin on the branches of A. araucana. Preliminary phylogenetic analyses placed isolates in the recently described sub-class Cryptocaliciomycetidae, closest to Cryptocalicium blascoi. However, the morphology of the ascomata and its occurrence in a unique niche suggested that the closest relative could be Resinogalea humboldtensis (Bruceomycetaceae, incertae sedis), a fungus with similar sporing structures found on resin of Araucaria humboldtensis in New Caledonia. There are no living cultures or sequence data available for either R. humboldtensis or its supposed closest relative, Bruceomyces castoris, precluding sequence-based comparisons. Morphological comparisons of the sporing structures on A. araucana confirmed that the ascomatal morphology of our unknown calicioid fungus and R. humboldtensis are almost identical and resemble each other more so than B. castoris or Cr. blascoi. A phylogenetic analysis based on the small subunit (SSU), internal transcribed spacer (ITS) and large subunit (LSU) rDNA regions resolved our strains into two clades with Cr. blascoi as its closest relative. Further analyses applying the Genealogical Concordance Phylogenetic Species Recognition (GCPSR) based on ITS, mini chromosome maintenance protein complex (MCM7), RNA polymerase II second largest subunit (RPB2) and translation elongation factor 1-alpha (TEF) gene regions, confirmed that strains represent two new species. Based on our morphological observations and phylogenetic analyses, we introduce two new Resinogalea species, R. araucana and R. tapulicola, and reclassify the genus in the subclass Cryptocaliciomycetidae.