bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spike-specific TCRβ repertoire shows distinct features in unvaccinated or vaccinated patients with SARS-CoV-2 infection
Authors: Vecchio Eleonora , Rotundo Salvatore , Veneziano Claudia , Abatino Antonio , Aversa Ilenia , Gallo Raffaella , Giordano Caterina , Serapide Francesca , Fusco Paolo , Viglietto Giuseppe , Cuda Giovanni , Costanzo Francesco , Russo Alessandro , Trecarichi Enrico Maria , Torti Carlo , Palmieri Camillo 
Published: January 2024

Abstract
Background
The evolving variants of SARS-CoV-2 may escape immunity from prior infections or vaccinations. It’s vital to understand how immunity adapts to these changes. Both infection and mRNA vaccination induce T cells that target the Spike protein. These T cells can recognize multiple variants, such as Delta and Omicron, even if neutralizing antibodies are weakened. However, the degree of recognition can vary among people, affecting vaccine efficacy. Previous studies demonstrated the capability of T-cell receptor (TCR) repertoire analysis to identify conserved and immunodominant peptides with cross-reactive potential among variant of concerns. However, there is a need to extend the analysis of the TCR repertoire to different clinical scenarios. The aim of this study was to examine the Spike-specific TCR repertoire profiles in natural infections and those with combined natural and vaccine immunity.

Methods
A T-cell enrichment approach and bioinformatic tools were used to investigate the Spike-specific TCRβ repertoire in peripheral blood mononuclear cells of previously vaccinated (n = 8) or unvaccinated (n = 6) COVID-19 patients.

Results
Diversity and clonality of the TCRβ repertoire showed no significant differences between vaccinated and unvaccinated groups. When comparing the TCRβ data to public databases, 692 unique TCRβ sequences linked to S epitopes were found in the vaccinated group and 670 in the unvaccinated group. TCRβ clonotypes related to spike regions S135-177, S264-276, S319-350, and S448-472 appear notably more prevalent in the vaccinated group. In contrast, the S673-699 epitope, believed to have super antigenic properties, is observed more frequently in the unvaccinated group. In-silico analyses suggest that mutations in epitopes, relative to the main SARS-CoV-2 variants of concern, don’t hinder their cross-reactive recognition by associated TCRβ clonotypes.

Conclusions
Our findings reveal distinct TCRβ signatures in vaccinated and unvaccinated individuals with COVID-19. These differences might be associated with disease severity and could influence clinical outcomes.
Trial registration: FESR/FSE 2014–2020 DDRC n. 585, Action 10.5.12, noCOVID19@UMG.
Multi-institutional prognostic modeling of survival outcomes in NSCLC patients treated with first-line immunotherapy using radiomics
Authors: Yolchuyeva Sevinj , Ebrahimpour Leyla , Tonneau Marion , Lamaze Fabien , Orain Michele , Coulombe François , Malo Julie , Belkaid Wiam , Routy Bertrand , Joubert Philippe , Manem Venkata SK. 
Published: January 2024

Abstract
Background
Immune checkpoint inhibitors (ICIs) have emerged as one of the most promising first-line therapeutics in the management of non-small cell lung cancer (NSCLC). However, only a subset of these patients responds to ICIs, highlighting the clinical need to develop better predictive and prognostic biomarkers. This study will leverage pre-treatment imaging profiles to develop survival risk models for NSCLC patients treated with first-line immunotherapy.

Methods
Advanced NSCLC patients (n = 149) were retrospectively identified from two institutions who were treated with first-line ICIs. Radiomics features extracted from pretreatment imaging scans were used to build the predictive models for progression-free survival (PFS) and overall survival (OS). A compendium of five feature selection methods and seven machine learning approaches were utilized to build the survival risk models. The concordance index (C-index) was used to evaluate model performance.

Results
From our results, we found several combinations of machine learning algorithms and feature selection methods to achieve similar performance. K-nearest neighbourhood (KNN) with ReliefF (RL) feature selection was the best-performing model to predict PFS (C-index = 0.61 and 0.604 in discovery and validation cohorts), while XGBoost with Mutual Information (MI) feature selection was the best-performing model for OS (C-index = 0.7 and 0.655 in discovery and validation cohorts).

Conclusion
The results of this study highlight the importance of implementing an appropriate feature selection method coupled with a machine learning strategy to develop robust survival models. With further validation of these models on external cohorts when available, this can have the potential to improve clinical decisions by systematically analyzing routine medical images.
Chorioamnionitis accelerates granule cell and oligodendrocyte maturation in the cerebellum of preterm nonhuman primates
Authors: Newman Josef , Tong Xiaoying , Tan April , Yeasky Toni , De Paiva Vanessa Nunes , Presicce Pietro , Kannan Paranthaman S. , Williams Kevin , Damianos Andreas , Tamase Newsam Marione , Benny Merline K. , Wu Shu , Young Karen C. , Miller Lisa A. , Kallapur Suhas G. , Chougnet Claire A. , Jobe Alan H. , Brambilla Roberta , Schmidt Augusto F. 
Published: January 2024

AbstractBackgroundPreterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar underdevelopment, but the mechanisms of disrupted cerebellar development in preterm infants are not well understood. The cerebellum is consistently affected in people with autism spectrum disorders, showing reduction of Purkinje cells, decreased cerebellar grey matter, and altered connectivity.MethodsPreterm rhesus macaque fetuses were exposed to intra-amniotic LPS (1 mg,E. coliO55:B5) at 127 days (80%) gestation and delivered by c-section 5 days after injections. Maternal and fetal plasma were sampled for cytokine measurements. Chorio-decidua was analyzed for immune cell populations by flow cytometry. Fetal cerebellum was sampled for histology and molecular analysis by single-nuclei RNA-sequencing (snRNA-seq) on a 10× chromium platform. snRNA-seq data were analyzed for differences in cell populations, cell-type specific gene expression, and inferred cellular communications.ResultsWe leveraged snRNA-seq of the cerebellum in a clinically relevant rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation, and to oligodendrocytes, which show accelerated maturation from pre-oligodendrocytes into myelinating oligodendrocytes.ConclusionThese findings suggest a role of chorioamnionitis on disrupted cerebellar maturation associated with preterm birth and on the pathogenesis of neurodevelopmental disorders among preterm infants.
Effect of dolutegravir-based versus efavirenz-based antiretroviral therapy on excessive weight gain in adult treatment-naïve HIV patients at Matsanjeni health center, Eswatini: a retrospective cohort study
Authors: Mukuna Didier M. , Decroo Tom , Nyapokoto Clara M. 
Published: January 2024

Abstract
Background
There is limited data on dolutegravir (DTG)-associated weight gain from settings with a dual burden of HIV and overnutrition.

Methods
In Eswatini (at Matsanjeni), among 156 and 160 adult patients on DTG-based and EFV-based antiretroviral therapy (ART), respectively, we studied excessive weight gain (BMI at 24 months ART greater than baseline and ≥25 kg/m2).

Results
The median BMI increase in DTG-based patients was 1.09 (IQR:-0.28,3.28) kg/m2 compared to 0.20 (IQR:-0.85,2.18) kg/m2 in EFV-based patients (p value = 0.001). DTG-based ART predicted excessive weight gain (aOR 2.61;95% CI:1.39–4.93).

Conclusion
Practitioners should consider DTG-based regimens as one of the risk factors for overweight/obesity.
EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening
Authors: Cappelletto Ambra , Alfì Edoardo , Volf Nina , Vu Thi Van Anh , Bortolotti Francesca , Ciucci Giulio , Vodret Simone , Fantuz Marco , Perin Martina , Colliva Andrea , Rozzi Giacomo , Rossi Matilde , Ruozi Giulia , Zentilin Lorena , Vuerich Roman , Borin Daniele , Lapasin Romano , Piazza Silvano , Chiesa Mattia , Lorizio Daniela , Triboli Luca , Kumar Sandeep , Morello Gaia , Tripodo Claudio , Pinamonti Maurizio , Piperno Giulia Maria , Benvenuti Federica , Rustighi Alessandra , Jo Hanjoong , Piccolo Stefano , Del Sal Giannino , Carrer Alessandro , Giacca Mauro , Zacchigna Serena 
Published: January 2024

Abstract
Background
New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them are doomed to fail in clinical trials, largely because they are identified by cellular or in silico screens that cannot predict their in vivo effect.

Methods
We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly in vivo in a mouse model of cancer and validated the therapeutic effect of the first hit, EMID2, in both orthotopic and genetic models of lung and pancreatic cancer.

Results
EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival of patients with high levels of EMID2 expression in the most aggressive human cancers. Mechanistically, EMID2 inhibited TGFβ maturation and activation of cancer-associated fibroblasts, resulting in more elastic ECM and reduced levels of YAP in the nuclei of cancer cells.

Conclusion
This is the first in vivo screening, precisely designed to identify proteins able to interfere with cancer cell invasiveness. EMID2 was selected as the most potent protein, in line with the emerging relevance of the tumor extracellular matrix in controlling cancer cell invasiveness and dissemination, which kills most of cancer patients.
Intra-aortic balloon pump still has a role in late-onset myocardial infarction complicated by ventricular septal rupture with intractable heart failure: a case report
Authors: Alsagaff Mochamad Yusuf , Revianto Oky , Sembiring Yan Efrata , Ilman Muhammad Insani , Intan Ryan Enast 
Published: January 2024

Abstract
Background
The current guidelines have discouraged the routine use of intra-aortic balloon pump (IABP) in cardiogenic shock complicating acute coronary syndrome (ACS). Since then, the trend of IABP utilization in ACS has been declining. Nevertheless, the guidelines still preserve the recommendation of IABP use in hemodynamic instability or cardiogenic shock caused by post myocardial infarction (MI) ventricular septal rupture (VSR).

Case presentation
A 46-years-old diabetic Southeast Asian female was referred from a peripheral facility with intractable heart failure despite treatment with vasoactive agents and diuretics for five days. The ECG suggested a recent anteroseptal myocardial infarction with normal high-sensitivity troponin-I value. The echocardiography detected a regional wall motion abnormality and a 10 mm wide ventricular septal defect. Invasive coronary angiography revealed a severe two-vessel coronary artery disease. We planned a delayed surgical strategy with preoperative optimization using IABP as a bridge to surgery. IABP implantation followed by significant hemodynamic improvement and rapid resolution of heart failure without any inotrope support. Afterwards, coronary artery bypass grafting (CABG) and VSR surgical repair were performed. We safely removed IABP on the third postoperative day with proper weaning and minimal vasoactive support.

Conclusion
We report a case where IABP still provided benefits for a patient with intractable heart failure caused by undetermined onset MI complicated by VSR. The use of IABP in such a case is in accordance with the recommendation of the current guidelines. Several studies showed that IABP use during preoperative optimization in the case of post-MI VSR was associated with survival benefits.
Investigating environmental transmission to resolve a Bacillus cereus group outbreak in a neonatal intensive care unit using core genome multilocus sequence typing
Authors: Tönnies Hauke , Heep Axel , Herrmann Jörg , Lange Matthias , Mellmann Alexander , Hamprecht Axel 
Published: January 2024

Abstract
Background
We analyzed an outbreak of Bacillus cereus group (Bcg) at a single-center neonatal intensive care unit level IV by conducting comprehensive sampling of both patients and the environment.

Methods
Between 06/2020 and 10/2021, all Bcg isolates identified by both regular colonization screening and additional sampling of the environment were subjected to whole-genome sequencing, followed by in vitro extraction of MLST ST, resistance genes and virulence factors. Using publicly available genome sequences, we defined an ad hoc core genome multilocus sequence typing (cgMLST) scheme comprising 2759 target genes for Bcg typing, which we applied to the detected isolates. We have compared the results with a stable cgMLST that was published in the meantime and completed the investigation with a SNP analysis.

Results
We analyzed 28 Bcg isolates from patient and environmental samples using MLST and cgMLST. This revealed multiple sequence types, with ST127 being the most common (n = 13). Both cgMLST schemes grouped ten of the 13 ST127 isolates into a cluster, including two invasive isolates from two different patients and several environmental samples. SNP analysis postulated a screen from a ventilation machine as a possible reservoir.

Conclusion
In sensitive settings such as neonatal intensive care units, considering the environment in outbreak analyses is crucial, especially when investigating potential transmission routes through shared devices. When dealing with widespread bacteria such as Bcg, high-resolution typing techniques are necessary. In this study, we successfully resolved an outbreak of Bcg infections using a custom cgMLST scheme combined with a SNP analysis.
Analysis of customer reviews with an improved VADER lexicon classifier
Authors: Barik Kousik , Misra Sanjay 
Published: January 2024

Abstract
Background
The importance of customer reviews in determining satisfaction has significantly increased in the digital marketplace. Using sentiment analysis in customer reviews has immense potential but encounters challenges owing to domain heterogeneity. The sentiment orientation of words varies by domain; however, comprehending domain-specific sentiment reviews remains a significant constraint.

Aim
This study proposes an Improved VADER (IVADER) lexicon-based classification model to evaluate customer sentiment in multiple domains. The model involves constructing a domain-specific dictionary based on the VADER lexicon and classifying doeviews using the constructed dictionary.

Methodology
The proposed IVADER model uses data preprocessing, Vectorizer transformation, WordnetLemmatizer-based feature selection, and enhanced VADER Lexicon classifier.

Result
Compared to existing studies, the IVVADER model accomplished outcomes of accuracy of 98.64%, precision of 97%, recall of 94%, f1-measure of 92%, and less training time of 44 s for classification.

Outcome
Product designers and business organizations can benefit from the IVADER model to evaluate multi-domain customer sentiment and introduce new products in the competitive online marketplace.
Safety and Efficacy of Denosumab in Children With Osteogenesis Imperfecta—the First Prospective Comparative Study
Authors: Liu Jiayi , Lin Xiaoyun , Sun Lei , Zhang Qian , Jiang Yan , Wang Ou , Xing Xiaoping , Xia Weibo , Li Mei 
Published: January 2024

Abstract

Context
Denosumab is a potential therapeutic agent for osteogenesis imperfecta (OI), but its efficacy and safety remain unclear in children with OI.

Objective
We aimed to investigate the effects of denosumab on bone mineral density (BMD), spinal morphometry, and safety in children with OI compared with zoledronic acid.

Methods
In this prospective study, 84 children or adolescents with OI were randomized to receive denosumab subcutaneous injection every 6 months or zoledronic acid intravenous infusion once. Changes of BMD and its Z-score, vertebral shape, serum levels of calcium and bone turnover biomarkers were assessed during the 1-year treatment.

Results
After 12 months of treatment, BMD at the lumbar spine, femoral neck, and total hip significantly increased by 29.3%, 27.8%, and 30.2% in the denosumab group, and by 32.2%, 47.1%, and 41.1% in the zoledronic acid group (all P &lt; .001 vs baseline). Vertebral height and projection area significantly increased after denosumab and zoledronic acid treatment. Rebound hypercalcemia was found to be a common and serious side effect of denosumab, of which 14.3% reached hypercalcemic crisis. Rebound hypercalcemia could be alleviated by switching to zoledronic acid treatment.

Conclusion
Treatment with denosumab or zoledronic acid is beneficial in increasing BMD and improving the spinal morphometry of children with OI. However, denosumab should be used with caution in pediatric patients with OI because of its common and dangerous side effect of rebound hypercalcemia. The appropriate dosage and dosing interval of denosumab need to be further explored in children with OI.
Imaging of Pheochromocytomas and Paragangliomas
Authors: Timmers Henri J L M , Taïeb David , Pacak Karel , Lenders Jacques W M 
Published: January 2024

Abstract
Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
Clinical and Pathological Predictors of Death for Adrenocortical Carcinoma
Authors: Pato Eduardo , Srougi Victor , Zerbini Claudia , Ledesma Felipe L , Tanno Fabio , Almeida Madson Q , Nahas William , Latronico Ana Claudia , Mendonca Berenice B , Chambô Jose L , Fragoso Maria Candida B V 
Published: January 2024

Abstract
Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority presented as European Network for the Study of Adrenal Tumors (ENSAT) III or IV (22.9% and 31.2%, respectively), and the overall mortality rate was 54.6%. Independent predictors of death were elevated secretion of cortisol (HR = 2.0), androstenedione (HR = 2.2), estradiol (HR = 2.8), 17-OH progesterone (HR = 2.0), and 11-deoxycortisol (HR = 5.1), higher Weiss (HR = 4.3), modified Weiss (HR = 4.4), and Helsinki scores (HR = 12.0), advanced ENSAT stage (HR = 27.1), larger tumor size (HR = 2.7), higher Ki-67 percentage (HR = 2.3), and incomplete surgical resection (HR = 2.5). Mitosis greater than 5/50 high-power field (HR = 5.6), atypical mitosis (HR = 2.3), confluent necrosis (HR = 15.4), venous invasion (HR = 2.8), and capsular invasion (HR = 2.4) were also identified as independent predictors of death. Knowing the risk factors for ACC's mortality may help determine the best treatment option.
Kisspeptin Regulates Cell Invasion and Migration in Endometrial Cancer
Authors: Wu Hsien-Ming , Chen Liang-Hsuan , Chiu Wei-Jung , Tsai Chia-Lung 
Published: January 2024

Abstract
Kisspeptin (a product of the KISS1 gene and its receptor) plays an important role in obstetrics, gynecology, and cancer cell metastasis and behavior. In hypothalamic-pituitary-gonadal axis and placentation, Kisspeptin/Kisspeptin receptor affects hormone release and represses trophoblast invasion into maternal deciduae. Endometrial cancer is one of the common gynecological cancers and is usually accompanied by metastasis, the risk factor that causes death. Recently, research has demonstrated that Kisspeptin/Kisspeptin receptor expression in aggressive-stage endometrial cancer tissues. However, the detailed mechanism of Kisspeptin/Kisspeptin receptor in regulating the motility of endometrial cancers is not well understood. In this study, we use endometrial cancer cell lines RL95-2, Ishikawa, HEC-1-A, and HEC-1-B as models to explore the molecular mechanism of Kisspeptin on cell motility. First, we discovered that Kisspeptin/Kisspeptin receptor was expressed in endometrial cancer cells, and Kisspeptin significantly regulated the migration and invasion of endometrial cancer cells. Furthermore, we explored the epithelial–mesenchymal transition marker expression and the underlying signals were regulated on Kisspeptin treatment. In conclusion, we suggest that Kisspeptin regulates endometrial cancer cell motility via FAK and Src expression and the ERK1/2, N-Cadherin, E-Cadherin, beta-Catenin, Twist, and matrix metalloproteinase signaling pathways. We expect these molecules could be candidates for the development of new approaches and therapeutic targets.