bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience
Authors: Svedman Fernanda Costa , Holmsten Karin , Jawdat Faith , Hailom Wehazit , Alm Daniel , Grozman Vitali , Ullén Anders 
Published: June 2024

Abstract
Background
Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population.

Methods
All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT.

Results
In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81–9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT.

Conclusions
SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.
Incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated haemophilia A
Authors: Wang Han , Zhu Wei , Wang Shujie , Feng Bin , Weng Xisheng 
Published: June 2024

Abstract
Introduction
Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by lack or deficiency of coagulation factor VIII.

Aim
The aim of this study is to determine the incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated persons with HA.

Methods
A total of 151 HA who underwent 221 major orthopaedic surgical procedures after intensive FVIII treatment were reviewed. The results of inhibitor tests were collected. Potential clinical risk factors for inhibitor development were analyzed.

Results
111 people were diagnosed with severe HA. Thirty-seven persons (24.5%) had history of previous intensive FVIII treatment for surgical procedure. They received a mean perioperative cumulative FVIII of 498 iu/kg within first week after surgery. Seven cases (4.6%) developed an inhibitor post-operatively in our study. Surgical procedure for pseudotumor and the group of persons who experienced postoperative complications had the higher incidence of inhibitor development (9.5%, 13.3% respectively). Only previous history for intensive FVIII exposure was considered as a significant predictor for postoperative inhibitor development after multivariate logistic regression analysis (OR: 29.5, P = 0.002).

Conclusion
The incidence of inhibitor development in previously treated persons with HA undergoing major orthopaedic surgery was 4.6% and the history of previous intensive FVIII treatment for surgery was associated with higher risk of inhibitor development.
Alterations in DNA methylation machinery in a rat model of osteoarthritis of the hip
Authors: Kawarai Yuya , Nakamura Junichi , Hagiwara Shigeo , Suzuki-Narita Miyako , Inage Kazuhide , Ohtori Seiji 
Published: June 2024

Abstract
Background
This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models.

Methods
Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated.

Results
The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten–eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups.

Conclusions
The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.
The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1
Authors: Yang Miaomiao , Wei Yujie , He Xin , Xia Changwei 
Published: June 2024

Abstract
Background
There is growing evidence indicating that deubiquitinating enzymes may contribute to tumor progression and can serve as promising therapeutic targets.

Methods
The overexpression of deubiquitinase OTUD6B in lung adenocarcinoma (LUAD) and its adjacent tissues was analyzed by immunohistochemistry and TCGA/GO database. Survival analysis further supported OTUD6B as a potential target for LUAD treatment. We assessed the effect of OTUD6B on LUAD cell growth using cell viability assays and conducted TUNEL staining, migration, and invasion experiments to investigate the impact of OTUD6B on the apoptosis and metastasis of LUAD cells. Additionally, we established a transplanted tumor model in nude mice to validate our findings in vivo. Finally, using IP mass spectrometry and co-IP experiments, we screened and confirmed the influence of RIPK1 as a substrate of OTUD6B in LUAD.

Results
OTUD6B is highly overexpressed in human LUAD and predicts poor prognosis in LUAD patients. OTUD6B knockdown inhibited the proliferation of LUAD cells and enhanced apoptosis and inhibited metastasis in LUAD cells suppressed. A549 xenografts revealed that OTUD6B deletion can slow down tumour growth. Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability.

Conclusions
Our results suggest that OTUD6B is a promising clinical target for LUAD treatment and that targeting OTUD6B may constitute an effective anti-LUAD strategy.
Dirus complex species identification PCR (DiCSIP) improves the identification of Anopheles dirus complex from the Greater Mekong Subregion
Authors: Saeung Manop , Pengon Jutharat , Pethrak Chatpong , Thaiudomsup Saranya , Lhaosudto Suthat , Saeung Atiporn , Manguin Sylvie , Chareonviriyaphap Theeraphap , Jupatanakul Natapong 
Published: June 2024

Abstract
Background
The Anopheles dirus complex plays a significant role as a malaria vector in the Greater Mekong Subregion (GMS), with varying degrees of vector competence among species. Accurate identification of sibling species in this complex is essential for understanding malaria transmission dynamics and deploying effective vector control measures. However, the original molecular identification assay, Dirus allele-specific polymerase chain reaction (AS-PCR), targeting the ITS2 region, has pronounced nonspecific amplifications leading to ambiguous results and misidentification of the sibling species. This study investigates the underlying causes of these inconsistencies and develops new primers to accurately identify species within the Anopheles dirus complex.

Methods
The AS-PCR reaction and thermal cycling conditions were modified to improve specificity for An. dirus member species identification. In silico analyses with Benchling and Primer-BLAST were conducted to identify problematic primers and design a new set for Dirus complex species identification PCR (DiCSIP). DiCSIP was then validated with laboratory and field samples of the An. dirus complex.

Results
Despite several optimizations by reducing primer concentration, decreasing thermal cycling time, and increasing annealing temperature, the Dirus AS-PCR continued to produce inaccurate identifications for Anopheles dirus, Anopheles scanloni, and Anopheles nemophilous. Subsequently, in silico analyses pinpointed problematic primers with high Guanine-Cytosine (GC) content and multiple off-target binding sites. Through a series of in silico analyses and laboratory validation, a new set of primers for Dirus complex species identification PCR (DiCSIP) has been developed. DiCSIP primers improve specificity, operational range, and sensitivity to identify five complex member species in the GMS accurately. Validation with laboratory and field An. dirus complex specimens demonstrated that DiCSIP could correctly identify all samples while the original Dirus AS-PCR misidentified An. dirus as other species when used with different thermocyclers.

Conclusions
The DiCSIP assay offers a significant improvement in An. dirus complex identification, addressing challenges in specificity and efficiency of the previous ITS2-based assay. This new primer set provides a valuable tool for accurate entomological surveys, supporting effective vector control strategies to reduce transmission and prevent malaria re-introducing in the GMS.

Graphical Abstract
PubChem synonym filtering process using crowdsourcing
Authors: Kim Sunghwan , Yu Bo , Li Qingliang , Bolton Evan E. 
Published: June 2024

AbstractPubChem (https://pubchem.ncbi.nlm.nih.gov) is a public chemical information resource containing more than 100 million unique chemical structures. One of the most requested tasks in PubChem and other chemical databases is to search chemicals by name (also commonly called a “chemical synonym”). PubChem performs this task by looking up chemical synonym-structure associations provided by individual depositors to PubChem. In addition, these synonyms are used for many purposes, including creating links between chemicals and PubMed articles (using Medical Subject Headings (MeSH) terms). However, these depositor-provided name-structure associations are subject to substantial discrepancies within and between depositors, making it difficult to unambiguously map a chemical name to a specific chemical structure. The present paper describes PubChem’s crowdsourcing-based synonym filtering strategy, which resolves inter- and intra-depositor discrepancies in synonym-structure associations as well as in the chemical-MeSH associations. The PubChem synonym filtering process was developed based on the analysis of four crowd-voting strategies, which differ in the consistency threshold value employed (60% vs 70%) and how to resolve intra-depositor discrepancies (a single vote vs. multiple votes per depositor) prior to inter-depositor crowd-voting. The agreement of voting was determined at six levels of chemical equivalency, which considers varying isotopic composition, stereochemistry, and connectivity of chemical structures and their primary components. While all four strategies showed comparable results, Strategy I (one vote per depositor with a 60% consistency threshold) resulted in the most synonyms assigned to a single chemical structure as well as the most synonym-structure associations disambiguated at the six chemical equivalency contexts. Based on the results of this study, Strategy I was implemented in PubChem’s filtering process that cleans up synonym-structure associations as well as chemical-MeSH associations. This consistency-based filtering process is designed to look for a consensus in name-structure associations but cannot attest to their correctness. As a result, it can fail to recognize correct name-structure associations (or incorrect ones), for example, when a synonym is provided by only one depositor or when many contributors are incorrect. However, this filtering process is an important starting point for quality control in name-structure associations in large chemical databases like PubChem.
Evaluation of gastrin-releasing peptide receptor, prostate-specific membrane antigen, and neurotensin receptor 1 as potential biomarkers for accurate prostate cancer stratified diagnosis
Authors: Xiao Ling , Fang Zhihui , Tang Yongxiang , Sun Yanyan , Zhu Zehua , Li Jian , Zhou Ming , Yang Nengan , Zheng Kai , Hu Shuo 
Published: June 2024

Abstract
Background
Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging.

Methods
In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT.

Results
In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of 68Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of 68Ga-NOTA-RM26 than those with high GS (P = 0.001).

Conclusions
This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.
Analysis of Aspergillus niger isolated from ancient palm leaf manuscripts and its deterioration mechanisms
Authors: Chu Shimin , Lin Lanying , Tian Xingling 
Published: June 2024

Abstract
Palm leaf manuscripts (PLMs), venerable historical artefacts containing Buddhist scriptures, history, mathematics and literature, which are carried by palm leaves (Corypha umbraculifera) and are highly susceptible to microbial degradation during prolonged storage. This degradation results in significant alterations to both the appearance and material properties of PLMs, but the precise mechanism underlying this deterioration remains a mystery. To this end, the present study focused on ancient PLMs from Xishuangbanna Dai Autonomous Prefecture in Yunnan Province, China. The objective of present study was to isolate, culture and identify the microorganisms typically found in these manuscripts and to use them to biodegrade the carriers of PLMs. Detailed observations of the biodegradation behavior of these microorganisms on the carriers of PLMs were carried out, together with characterizations of the hierarchical structure and mechanical properties of the leaf fiber cell walls. This comprehensive analysis provided insights into the deterioration mechanisms of the carriers of PLMs. The study revealed the presence of the common fungus Aspergillus niger on ancient PLMs. Aspergillus niger can secrete cellulase, lipase, and acidic substances after colonizing on the carriers of PLMs. These substances sequentially damage the carrier's epidermal cells, mesophyll cells, and leaf fibers, leading to the separation of different tissue structures. At the molecular level, the lipids on the surface of the leaves were degraded initially, and sequential depolymerization of hemicellulose, amorphous cellulose, and crystalline cellulose occurred. Additionally, this study firstly applied nanoindentation technology in the research of PLMs. The mechanical properties of the cell walls underwent notable alterations due to the modifications in chemical and crystalline structure of the carriers of PLMs upon the biodegradation of Aspergillus niger. Specifically, the hardness and elastic modulus of leaf fiber cell walls showed an initial increasing and then decreasing trend, consistent with the trend of cellulose crystallinity, which also provided a new reference for assessing the degree of deterioration of PLMs.
Quantifying the expansion rates of aftershock zones for magnitude-7 class earthquakes around the Japanese archipelago
Authors: Mitsui Yuta , Utagawa Yuya , Miyamoto Ayaka 
Published: June 2024

AbstractEarthquakes (mainshocks) trigger sequences of aftershocks, the frequency of which diminishes following a power-law decay, while the spatial domain of these aftershocks extends logarithmically over time. The delineation of the aftershock zone can be modulated by variables beyond the magnitude of the mainshock, encompassing the location of the fault (whether the fault is at a plate boundary), the depth at which the event occurs, and the prevailing local stress conditions. Here, we evaluate the expansion rate of aftershock zones by analyzing earthquakes of magnitude-7 class in the vicinity of the Japanese archipelago. Prior studies have offered approximate assessments of expansion rates; however, our approach involves the utilization of a straightforward algorithm for the automated estimation of this metric, facilitating the compilation of a catalog. Across the dataset, no pronounced correlations were discerned between the expansion rate and other examined parameters. Yet, an inverse relationship is identified between the expansion rate and the b value of aftershocks for mainshocks occurring at plate boundaries. This observation suggests that the expansion rate of aftershock zones predominantly mirrors the stress field following the mainshock. Such a pattern is not detected in mainshocks occurring within the plate's interior. While the expansion rate of aftershock zones is likely influenced by various factors, aftershock zones may expand more rapidly with higher differential stress in areas surrounding hypocenters of major interplate earthquakes of magnitude 8 or 9.
Causes of child labor and working conditions in Ethiopia: evidence from temporary inter-rural child labor migrants from Sekela district
Authors: Zewdie Birhanu Mengist , Berlie Arega Bazezew , Mersha Linger Ayele 
Published: June 2024

AbstractChild labor migration is a critical issue that has received limited attention from academic and policy domains in many developing countries. This article analysis the causes of child labor migration and working conditions at the destination of temporary inter-rural child labor migration from Sekela district, Northwest Ethiopia. Mixed research methods is employed. Quantitative data is collected from randomly selected 204 respondents engaged in child labor migration. Focus group discussion, informal conversational interviews, and observation are also undertaken to gather qualitative data. Most child labor migrants participate in child labor migration due to localized economic constraints, which are reflected through a desire to have modern goods and cloth, food scarcity, and resource degradation. Also, the expansion of commercial farms at destination areas directly or indirectly due to the globalized market indicates that migrant children’s local labor cannot be delinked from material realities created by both national and international economic policy. The income from child labor migration supports children and their households’ livelihood, though it is at the expense of children’s education as well as exposure to worse working conditions at their destination in terms of exploitation, underpayment, malnutrition, breaching of an agreement by employers, and harassment. Hence, to exploit the benefits and minimize the risks, balanced measures should be taken at the origin and destination. Education programs should be supportive in increasing food productivity and assisting households to diversify their means of income by allowing them to participate in non-farm activities. It is also essential to the establishment of support groups in migrant destination places and the expansion of labor inspectorates who continuously supervise the safety of child labor migrants.
Speculative futures for higher education
Authors: Bayne Sian , Ross Jen 
Published: June 2024

AbstractThis paper uses speculative methods as a way of imagining futures for higher education in open, non-predictive ways. The complexity and ‘unknowability’ of the highly technologised, environmentally damaged and politically degraded futures we seem to be facing can mean that our conversations about the future of higher education have a tendency to spiral too quickly into dystopianism and hopelessness. Speculative methods can help open up new kinds of conversation capable of supporting active and fundamental hope. Working within a postqualitative framework, we argue that such approaches support the collaborative imagining of multiple alternatives, and represent a way of advocating for those that are preferable. The paper presents a series of speculative scenarios and microfictions focusing on worlds ruptured by climate change, artificial intelligence, revolution and the technological enhancement of humans, connecting each of these to current critical research focused on climate crisis, ‘big tech’, rising global injustice and ‘big pharma’. It emphasises the vital contribution and place of higher education within such futures, and advocates for speculative methods as an approach to maintaining hope.
Engaging for the future: challenge-based learning and stakeholder partnerships in sustainability education
Authors: Höffken Johanna , Lazendic-Galloway Jasmina 
Published: June 2024

AbstractThis paper aims to illustrate a mechanism and the impact of collaboration between academia and external stakeholders using a challenge-based learning (CBL) approach, with ill-defined open challenges as the starting point of the learning journey. The context of the study is a sequence of three connected courses that enabled students to address pressing sustainability challenges both in the Global South and the Global North in a variety of fields, such as health, urban living, agriculture and waste management. The courses aimed to equip students with knowledge and skills on how to tackle the challenges and design responsible innovations, as well as inspire them to make an impact in the world, while collaborating with external stakeholders. The insights gained from this study are that the courses effectively fostered critical thinking, organizational skills, and teamwork capabilities among students. The collaboration with external partners was particularly valued by the students for its relevance to their learning and potential career progression, as it allowed them to take ownership of the challenges to tackle, thereby enhancing motivation and deepening their learning experience. Furthermore, the courses were successful in enabling students to apply knowledge to real-world cases and engage in meaningful debates on responsible innovation and SDGs.