bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase III Randomized Clinical Trial: The Impact of Paclitaxel-Based Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (NLHIPEC) Followed by Sequential Intravenous Chemotherapy in Advanced High-Grade Serous Ovarian Cancer Patients - Interim Analysis of Safety and Immediate Efficacy from the C-HOC Trial
Authors: Wang Qun , Liu Hua , Shen Yuhong , Shen Lifei , Feng Weiwei 
Published: October 2023

AbstractObjectiveThis study evaluates the potential superiority of combining paclitaxel-based neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (NLHIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy (IV NACT) alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of a planned phase III trial.MethodsIn a single-center, open-label, phase III trial, FIGO stage IIIC-IVB HGSOC patients (FAGOTTI score ≥8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The NLHIPEC group received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the IV NACT group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). This partial analysis focuses on comparing adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS.ResultsAmong 65 enrolled patients, 39 NLHIPEC and 21 IV NACT patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between two groups. The NLHIPEC group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P=0.000). R0 resection rates in IDS were 69.2% (NLHIPEC) and 66.7% (IV NACT). R2 resection occurred in 2.6% (NLHIPEC) and 14.3% (IV NACT) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively.ConclusionsCombining NLHIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. NLHIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if NLHIPEC combined with IV NACT is superior to IV NACT alone Keyword: high-grade serous ovarian/fallopian tubecarcinoma (HGSOC); paclitaxel; neoadjuvant chemotherapy;hyperthermic intraperitoneal chemotherapy (HIPEC); chemotherapy response score (CRS).
Improving epileptogenic zone estimation using Bayesian inference on neural field models
Authors: Vattikonda Anirudh Nihalani , Woodman Marmaduke M. , Lemarechal Jean-Didier , Daini Daniele , Hashemi Meysam , Bartolomei Fabrice , Jirsa Viktor 
Published: October 2023

AbstractEpilepsy remains a significant medical challenge, particularly in drug-resistant cases where surgical intervention may be the only viable treatment option. Identifying the epileptogenic zone, the brain region responsible for seizure initiation, is a critical step in surgical planning. Combining dynamical system models and the neuroimaging data of epileptic patients in a Bayesian framework has previously been shown to be a promising approach to identify the epileptogenic zone. However, previous studies employed coupled neural mass models to describe the whole brain seizure dynamics and hence could only provide a highly coarse spatially estimate of the epileptogenic zone. In this study we propose an extension of the Bayesian virtual epileptic patient framework to a neural field model which could improve the spatial resolution by several orders. Performing model inversion using neural field models is a challenging task since: (i) it is computationally expensive to compute gradients over a neural field simulation and (ii) parameter space can be very high dimensional. We demonstrate that using pseudo-spectral methods and spherical harmonic transforms it is feasible to perform Bayesian model inversion on a neural field extension of the reduced Epileptor model. We found that the neural field extension not only improves the spatial resolution but also significantly reduces the number of false positives.
Misidentification ofPlasmodiummixed-infections leads to an overestimation of falciparum malaria
Authors: Deora Nimita , Pande Veena , Sinha Abhinav 
Published: October 2023

AbstractDespite the fact that malaria elimination is nearing in several countries, we continue to struggle with accurate diagnosis and thus treatment. The purpose of this study was to determine the rate ofPlasmodiumspecies misidentification (MI) by microscopy (MS). The study was based on previously published reports in which MS-PCR pairs were analysed to identifyPlasmodiummisidentification rates (by MS). Region- and species-wise misidentification rates were also estimated.A total of 2706 MS-PCR pairs were extracted from 16 different locations across 11 Indian states. MS-PCR pair analysis revealed 15% misidentification rate (408/2706). Surprisingly, microscopy misidentified more than 98% of mixed infections (400/405) as mono-infections (almost all asP. falciparummono infections). The study identifies Jharkhand and Madhya Pradesh as major contributors (>20%) toPlasmodiumspecies misidentification by microscopy. These findings suggest that we are overestimatingP. falciparumburden, potentially wasting elimination resources, and underestimating non-falciparum species. The study also addresses an important issue concerning analysis of misidentification & sub-microscopic infection data (SMI). The proposed analysis (for MI and SMI) will aid in deciphering MI and SMI data in a more granular manner, generating actionable data for elimination programmes in various countries.
Gene Therapy for Cardiomyopathy associated with Duchenne Muscular Dystrophy in a Pig Model
Authors: Bähr Andrea , Hoppmann Petra , Bozoglu Tarik , Stirm Michael , Luksch Ina , Ziegler Tilman , Hornaschewitz Nadja , Shrestha Samjhana , Shashikadze Bachuki , Stöckl Jan , Raad Nour , Blum Helmut , Krebs Stefan , Fröhlich Thomas , Baumgartner Christine , Nowak-Imialek Monika , Walter Maggie , Weber Christian , Engelhardt Stefan , Moretti Alessandra , Klymiuk Nik , Wurst Wolfgang , Laugwitz Karl-Ludwig , Hajjar Roger J. , Wolf Eckhard , Kupatt Christian 
Published: October 2023

AbstractBackgroundGenetic cardiomyopathies caused by mutations in the dystrophin gene(DMD)are only partially responsive to current pharmacological heart failure treatments, although dilated and arrhythomogenic phenotypes of cardiomyopathy are frequent.ObjectiveIn this study, we tested whether a normalization of Ca2+-handling by forced expression of SERCA2a in cardiomyocytes mitigates heart failure and arrhythmogenesis in a pig model for Duchenne muscular dystrophy (DMD).Methods and resultsMale offspring of pigs lackingDMDexon 52 are characterized by heart failure with reduced ejection fraction (HFrEF, EF 34.5±1.8% vs. 49.2±1.0% in control hearts), arrhythmogenesis due to large apical regions of reduced voltage amplitude and sudden cardiac death with a lifespan of usually less than 4 months. Slow antegrade intracoronary infusion of AAV1.SERCA2a (3×1013virus genomes (vg) per pig) improved left ventricular ejection fraction (EF 47.3±2.0%, p<0.05) to a similar extent as germline editing ofDMDΔ52 toDMDΔ51-52, inducing a Becker dystrophy (BMD) genotype (EF 46.7±3.8%). Moreover, AAV.SERCA2a significantly reduced myocardial inflammation and fibrosis and areas of reduced AP amplitude.ConclusionsInDMDpigs, 3×1013vg/heart of GMP-grade AAV1.SERCA2a sufficed to normalize left ventricular function and improved electrical vulnerability of the heart. Hence, AAV.SERCA2a may serve as a treatment option for DMD cardiomyopathy.
SABRE: Self-Attention Based model for predicting T-cell Receptor Epitope Specificity
Authors: Wang Zicheng , Shen Yufeng 
Published: October 2023

AbstractT cell receptors (TCR) recognize antigens on the surface of T cells, which is the critical event in the adaptive immune response to infection and vaccination. The ability to determine TCR-antigen recognition would benefit research in basic immunology and therapeutics. High-throughput experimental approaches for determining TCR-antigen specificity have produced valuable data, but the TCR-antigen pairing space is astronomically more significant than what can reached by experiments. Here, we describe a computational method for predicting TCR-antigen recognition, SABRE (Self-Attention-based Transformer Model for predicting T-cell Receptor-Epitope specificity). SABRE captures sequence properties of matching TCR and antigen pairs by selfsupervised pre-training using known pairs from curated databases and large-scale experiments. It then fine-tunes by supervised learning to predict TCRs that can recognize each antigen. We showed that SABRE’s AUROC reaches 0.726 ± 0.008 for predicting TCR-epitope recognition. We meticulously designed a training and testing scheme to evaluate the model’s performance on unseen TCR species: 60% of the data was allocated for training, 20% for validation, and the remaining 20% exclusively for testing. Notably, this testing set comprised entirely of TCRs not present in the training phase, ensuring a genuine assessment of the model’s ability to generalize to novel data.
Hypoxia increases the methylated histones to prevent histone clipping and redistribution of heterochromatin during Raf-induced senescence
Authors: Chang Soojeong , Moon Ramhee , Yim Sujin , Nam Dowoon , Lee Sang-Won , Choi Seunghyuk , Paek Eunok , Hur Junho K. , Nam Youhyun , Chang Rakwoo , Park Hyunsung 
Published: October 2023

ABSTRACTHypoxia increases histone methylation by inhibiting O2- and α-ketoglutarate- dependent histone lysine demethylases (KDMs). This study is the first to demonstrate how the hypoxic increment of methylated histones cross-talks with other epigenetic changes, such as histone clipping, and heterochromatin redistribution (senescence-associated heterochromatin foci, SAHF) found during oncogene-induced senescence (OIS). Raf activation in primary human fibroblasts IMR90 increased cathepsin L (CTSL)-mediated clipping of histone 3 (H3), H2B and H4 at H3 A21/T22, H2B T19/K20, and H4 G11/K12, respectively. Hypoxia protected H3 from CTSL by increasing histone methylation, especially at H3K23me3 without reducing the activity of CTSL. The maintenance of methylated histones is sufficient for protecting histones from CTSL, not sufficient but necessary for inhibiting SAHFs. Expression of cleaved H3 induces senescence even under hypoxia, suggesting that hypoxia disrupts this positive feedback loop of OIS by increasing histone methylation. Thus, hypoxia protects histones and chromatin from dramatic epigenetic changes by increasing histone methylation.Highlights✓Raf activation in primary fibroblasts increases cathepsin L-mediated cleavage of H3, H2B, and H4.✓Hypoxia inhibits OIS-induced histone clipping by maintaining methylated histones.✓Cleaved H3 induces senescence, even under hypoxia.
The longest intron rule
Authors: Dvorak Pavel , Hlavac Viktor , Hanicinec Vojtech , Rao Bhavana Hemantha , Soucek Pavel 
Published: October 2023

AbstractDespite the fact that long introns mean an energy and time burden for eukaryotic cells, they play an irreplaceable role in the diversification and regulation of protein production. A general feature is the accumulation of the longest introns closer to the start of protein-coding genes. Our work aimed to more closely characterize the genes in which the longest intron is only located in the second or third third of the gene. Data on the lengths of all introns in genes were extracted from the genomes of 4 vertebrates (human, mouse, chicken and zebrafish), nematode worm and yeast. With the genes divided according to the relative position of the longest intron, gene set enrichment analyses were performed, the results of which were then confronted with the results of randomly generated gene sets of the same size. The analyses show that among the genes associated with biological processes of ion transport across membranes, cell signaling or the development of multicellular organisms, there is a greater representation of genes with the longest intron in the first third. Conversely, among the genes associated with the processes of RNA processing and ribosome biogenesis, there are more genes with the longest intron in the second or third third. It is a newly discovered characteristic with more general validity among multicellular organisms.
Behavioural and Social Predictors of COVID-19 Vaccine Uptake among Persons with Disabilities in Kenya
Authors: Josphat Martin , Moraro Rogers , Omogi Jarim , Alasmari Abrar , Kanyangi Lennah , Mwema Rehema , Simiyu Sheillah , Kosgei Sarah 
Published: October 2023

AbstractThe uptake of the COVID-19 vaccine by persons with disabilities remains largely unknown in low-and middle-income countries. This evidence gap necessitates disability-focused research to inform improvements in access and inclusion in the last mile of COVID-19 vaccination programs and to support future programs for other vaccine-preventable diseases. We aimed to identify behavioural and social predictors of COVID-19 uptake among persons with disabilities in Kenya. This was a convergent parallel mixed method study that involved questionnaires (792), key informants interviews, and focus group discussions among persons with disabilities and key stakeholders (government actors and professional associations). Data were analysed using STATA statistical analysis software (version 14). Chi-square (X2) and Fisher’s exact tests were used to test for differences in categorical variables; multivariate regression analysis was employed to ascertain the factors that influence uptake of COVID-19 among persons with disabilities (PWDs) in Kenya. Approximately 59% of persons with disabilities reported to be fully vaccinated, with significant disparities noted among those with cognition (34.2%) and self-care (36.6%) impairments. Confidence in vaccine benefits (Adjusted odds ration [OR]; 11.3, 95% CI; 5.2-24.2), health worker recommendation (OR; 2.6, 95% CI; 1.8-3.7), employment (OR; 2.1, 95% CI; 1.4-3.1), perceived risk (OR; 2.0, 95% CI; 1.3-3.1), age and area of residence were statistically significant predictors of vaccine uptake among PWDs. The primary reasons for low uptake included perceived negative vaccine effects and lack of adequate information. No association was found between having a primary caregiver and/or assistive device, with COVID-19 vaccine uptake. Subsequent vaccination deployments should map and reach PWDs through relevant institutions of PWDs, and localized vaccination campaigns. Related communication strategies should leverage on behaviour change techniques that inspire confidence in vaccines, and on the credibility and trust in health workers to improve vaccine uptake.
The 21-base pair deletion mutant Calpain 3 does not inhibit wild-type Calpain 3 activity
Authors: Maitra Swati , Oh Seungjae , Choe Yun-Jeong , Kim JiHye , Kim Nam Chul 
Published: October 2023

ABSTRACTIntroductionCalpain 3 is one of the calpain protease family members, which is a calcium-dependent proteolytic enzyme predominantly expressed in skeletal muscle. Loss-of-function mutations in the Calpain 3 gene have been related to autosomal recessiveLimb-Girdle Muscular Dystrophy 1(LGMDR1), a common form of muscular dystrophy. Recently, the heterozygous 21-bp deletion mutation of the Calpain 3 gene has been reported to cause autosomal dominantLimb-Girdle Muscular Dystrophy 4(LGMDD4). According to its dominant inheritance pattern, it has been suggested that the deletion mutant proteins act in a dominant-negative manner. Therefore, we examined whether the mutant protein can suppress the activity of wild-type Calpain 3 and has any dominant toxicity in cell culture andin vivo Drosophilamodels.MethodsA human cell culture (HeLa cells) model with the transient transfection of human wild-type and mutant Calpain 3 andin vivo Drosophilamodels overexpressing wild-type and mutantDrosophilaCalpain A and B were utilized in this study to assess dominant effects of Calpain 3 21-bp deletion mutant. Western blot analysis was used to determine protein stability and catalytic activity in cell culture. External eye morphology and muscle integrity were examined to observe dominant toxicity inDrosophilamodels.ResultsThe 21-bp deletion mutation of Calpain 3 resulted in catalytic inactivation, which did not inhibit wild-type Calpain 3 autolytic and catalytic activity against Calpastatin in HeLa cells. In addition, the mutant protein was normally processed by wild-type Calpain 3. Overexpression of wild-type and deletion mutant Calpain 3 in theDrosophilaeye and muscles did not exhibit significant developmental and age-related dominant toxicity.DiscussionWe provide evidence that mutant Calpain 3 does not suppress wild-type Calpain 3 activity. Rather, it is a mutant lacking autocatalytic processing activity like many other loss-of-function Calpain 3 mutants causing LGMDR1. Our results implicate that the stability of the heteromeric mutant and wild-type Calpain 3 complexes may be affected without inhibiting the wild-type activity per se. However, a more thorough investigation is necessary to understand the molecular mechanism and dominant inheritance of the heterozygous 21-bp deletion mutation in LGMDD4.
Ethnic fashion designers, entrepreneurs and family businesses: an African marketing perspective
Authors: Singh Satyendra 
Published: October 2023

PurposeThe purpose of the perspective article is to review relevant literature on family business and ethnic fashion and establish links across identity (defined as culture, tradition, heritage and status) and fashion (color, design, pattern and fabric/texture) and internationalization (foreign market entry), and develop a conceptual model using the identity theory and qualitative method.Design/methodology/approachThis is a qualitative study by design. We used a systematic research and ethnographic method for this study. Specifically, the author used the participant observation aspect of ethnography to collect information and images relating to ethnic fashion. Ethnography is a well-established methodology widely used in social sciences research, including fashion.FindingsThe study's conceptual model proposes that (1) ethnic fashion mediates the identity-internationalization relationship, (2) knowledge transfer moderates the identity-ethnic fashion relationship and (3) family business size moderates the ethnic fashion-internationalization relationship. It is also revealed that a person's status can be judged by their dress and fashion in under two minutes.Research limitations/implicationsThis study is limited to the African continent, though it has 54 countries with a current population of about 1.5 billion people, which is expected to be roughly 2.5 billion by 2050.Practical implicationsImplications of the study for the entrepreneurs and family businesses are that they should realize the opportunities presented by ethnic African fashion and tap into the most crucial key to success—local design, color, fabric and patterns associated with meaning and messages. Cross-cultural collaborations and digital innovations can help the internationalization of African fashion while preserving local heritage and identity. Another implication is that quality and consistency in branding are equally essential to be on par with intentional luxury brands.Social implicationsThe social implication of the study is that culture and fashion are correlated and influence designers' creations, reflecting and conveying identity, status and societal values. Fashion allows people to express their identity, individuality and values. The proper fashion and outfit can boost mood, self-esteem and confidence, resulting in healthy social interaction and mental health. Fashion can also raise social issues (e.g. inclusiveness, diversity and gender by featuring various models and designs) and environmental issues (e.g. sustainable practices local and ethical production).Originality/valueThe paper synthesizes ethnic fashion in the context of family businesses in Africa, highlights specific examples of ethnic fashion of African people with the potential for internationalization and proposes future fashion perspectives for family businesses. It adds value in that it focuses on fashion family businesses in the African continent.
Transforming entrepreneurial research: leveraging library research services and technology innovations for rapid information discovery
Authors: Gupta Varun , Gupta Chetna 
Published: October 2023

PurposeWith the aid of libraries, the research paper aims to assist businesses in swiftly and accurately acquiring knowledge and insights from scholarly literature to guide their inventive and decision-making processes. The foundation for achieving the goal is Connected Papers technology.Design/methodology/approachThe author's professional expertise in performing literature reviews using connected papers technology as well as using other ways, and corresponding with entrepreneurs and librarians impacted the article's research methodology.FindingsThe use of Connected Papers technology in the library context for helping entrepreneurs is discussed. Libraries and entrepreneurs could benefit from using Connected Papers technology to quickly compile pertinent data from scholarly literature to solve business challenges. According to the paper, adopting this technology can speed up information gathering and drastically reduce the time needed for business owners to search through bibliographic data-bases. Using this technology can help entrepreneurs at various phases of their entrepreneurial journeys and give libraries a productive way to assist business owners with their information needs.Originality/valueThis paper's novelty comes from its examination of the usage of connectedpapers.com technology to compile data from scholarly literature to assist entrepreneurs in solving their business problems. The useful piece of advice this paper offers entrepreneurs and librarians is what makes it valuable. By using connectedpapers.com technology, businesses may be able to get critical information from scholarly literature to foster a series of experimentation quickly and effectively. Also, librarians can help their patrons with systematic re-views and other research services by using this application.
Permission granted: professional development to promote social studies content integration
Authors: Brant Cathy A.R. , Stanger Ross 
Published: October 2023

PurposeIn this article, the authors, a university elementary social studies methods faculty member and a district social studies supervisor, discuss the creation of sustained professional development (PD) for elementary teachers on integrated social studies instruction.Design/methodology/approachThe authors detail the development of a PD sequence that included two 45-minute whole-group PD sessions and two days of individual and small-group school-day coaching for each school in the district. The ultimate goal of this PD was to provide the classroom teachers with the pedagogical content knowledge to meaningfully integrate social studies and English language arts (ELA) in their classrooms.FindingsThe collaboration between the university faculty member and the district administrator allowed for the development of meaningful, sustained PD for the classroom teachers.Originality/valueThis work has implications related to the development of PD to integrate social studies and ELA for university faculty working with teachers in school-based settings and for school administrators seeking to provide more PD for their teachers.