bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced MRI Prediction Model for Anatomical Site Identification in Uterine Carcinoma: Enhancing Diagnostic Accuracy and Treatment Planning
Authors: Malek Mahrooz , moayeri Moneereh , Akhavan Setareh , Hasani Shahrzad Sheikh , Nili Fatemeh , Mahboubi-Fooladi Zahra 
Published: April 2024

AbstractIntroductionThe uterine carcinoma is the most commonly diagnosed malignancy in female pelvis. Accurate identification of tumor origin is crucial for determining appropriate treatment approaches. This study aims to develop a prediction model using multiple MRI parameters to accurately diagnose uterine cancer with an indistinctive origin and those involving both the endometrium and cervix prior to treatment.Material and methodsThis prospective cohort study was conducted from January 2020 to January 2021, and included patients aged 20-80 who were newly diagnosed with uterine carcinoma who underwent MRI and were considered for hysterectomy within 6 months after MRI.ResultsIn our study, a total of 78 patients with uterine carcinoma were enrolled. the final diagnosis was confirmed as follows: 20 were adenocarcinoma of the cervix, 27 were SCC of the cervix, and 31 were endometrial adenocarcinoma. Certain imaging features were found to be consistent with cervical carcinoma, included parametrial invasion (69.6%), vaginal invasion (66%), stromal invasion (95.7%), and peripheral rim enhancement (68.9%). On post-contrast sequences, cervical cancer appeared hyperintense compared to the myometrium, while endometrial cancer appeared hypointense (96.8%). Endometrial carcinoma was well diagnosed by the presence of an endometrial cavity mass (100%), deep myometrium invasion (>50%) (54.8%), and a greater size in the craniocaudal dimension compared to the transverse dimension (100%).DiscussionThe study found that certain morphologic features were reliable indicators for detecting cervical carcinoma, including vaginal, stromal, and parametrial invasions, the presence of hypervascularity and peripheral rim enhancement. On the other hand, myometrial invasion and the presence of a mass in the endometrial cavity were significantly higher in endometrial carcinoma.
Glutaredoxin 3 (GLRX3) confers a fusion oncogene-dependent vulnerability to Ewing sarcoma
Authors: Vinca Endrit , Ehlers Anna C. , Ritter Alina , Obermeier David , Funk Cornelius M. , Geyer Florian H. , Schmucker Melissa , Li Jing , Zimmermann Malenka , Ceranski A. Katharina , Fuchslocher Fabia , Mertens Christina , Qiu Ruiyue , Muckenthaler Martina M. , Dahlhaus Alina , von Karstedt Silvia , Imle Roland , Banito Ana , Alonso Javier , Peterziel Heike , Witt Olaf , Oehme Ina , Cidre-Aranaz Florencia , Grünewald Thomas G. P. , Ohmura Shunya 
Published: April 2024

ABSTRACTEwing sarcoma (EwS) is a highly aggressive bone and soft-tissue associated cancer for which there are no effective targeted therapeutics available. Genetically, EwS is driven by aberrantly active EWSR1::ETS fusion transcription factors, most commonly EWSR1::FLI1. Despite their unique expression in EwS, all attempts to effectively target these fusion oncoproteins clinically were not yet successful, wherefore alternative targets are required.Here, we functionally characterize the evolutionarily conserved oxidative stress regulator glutaredoxin 3 (GLRX3) as a EwS-specific and EWSR1::FLI1-dependent vulnerability. Through integration of transcriptome-profiling, conditional drug screens in 3D cultures, and functional experiments, we discover that GLRX3 promotes EwS growth in vitro and in vivo, and that it has a key role in mitigation of oxidative stress and maintenance of iron homeostasis. These GLRX3 functions can be exploited in both GLRX3-high and -low expressing EwS cells by targeted therapeutics including CDK4/6 inhibitors and inducers of apoptotic and ferroptotic cell death. Collectively, our results exemplify how the interplay of an evolutionarily conserved oxidative stress regulator with a dominant oncogene can promote malignancy but provide opportunities for predictive diagnostics and personalized therapy.
Evidence of SARS-CoV-2 JN.2.5 variant circulation in Rio de Janeiro, Brazil
Authors: de Menezes Mariane Talon , Velozo Camila de Almeida , Moreira Filipe Romero Rebello , Mariani Diana , Nascimento Érica Ramos dos Santos , Gonçalves Cássia Cristina Alves , Boullosa Lídia Theodoro , Cordeiro Thais Félix , Oliveira Gleidson Silva , Carneiro Maria Cecília da Cunha , Valdez Cinthia Francisca , Faria Natacha Cunha de Araujo , da Silva Bianca Ortiz , Galliez Rafael Mello , Rossi Átila Duque , Voloch Carolina Moreira , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar 
Published: April 2024

AbstractNew SARS-CoV-2 variants are continually emerging and have the potential to present challenges to public health responses worldwide. This report discusses the early detection of the lineage JN.2.5 (alias of B.1.1.529.2.86.1.2.5) in Rio de Janeiro, Brazil. The variant was identified in early 2024 through viral whole-genome sequencing and phylogenetic analysis, revealing that circulating strains present genetic similarities to sequences reported in Canada, Poland, Belgium, and England. While the circulation of diverse Omicron sub lineages has significantly impacted COVID-19 epidemiology in Brazil, the consequences of the circulation of the novel variant are uncertain. Considering its immunological escape capabilities and epidemiological behavior observed elsewhere, close monitoring of this variant epidemiology is recommended.
Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to Long COVID
Authors: Al Masoodi Wasim Talib Mahdi , Radhi Sami Waheed , Abdalsada Habiba Khdair , Niu Menqi , Al-Hakeim Hussein Kadhem , Maes Michael 
Published: April 2024

AbstractBackgroundLong COVID (LC) patients frequently suffer from neuropsychiatric symptoms, including depression, anxiety, and chronic fatigue syndrome (CFS), relabeled as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance key play a role in these physio-affective symptoms due to LC.AimsTo examine the associations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA) and Fibro-Fatigue (FF) Rating Scale scores and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), and damage biomarkers such as S100B and neuron-specific enolase (NSE) in 90 subjects 3-6 months after acute SARS-CoV-2 infection.ResultsLC patients show higher HAMD, HAMA, and FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B than participants without LC. The HAMD/HAMA/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) – oxygen saturation (SpO2) (PBT/SpO2 index) during the acute infectious phase. A large part of the variance in the affective and CFS symptoms (33.6%-42.0%) was explained by a combination of biomarkers; the top-3 most important biomarkers were GAL-GALR1 signaling, PGE2, and CRP. Inclusion of the PBT/SpO2 index increased the prediction considerably (55.3%-67.1%). The PBT/SpO2 index predicted the increases in GAL-GALR1 signaling.ConclusionsThese findings suggest that the affective symptoms and CFS of Long COVID are largely the consequence of activated immune-inflammatory pathways, metabolic aberrations, and the severity of the inflammation during acute SARS-CoV-2 infection.
Incidence and risk factors associated with acquired syphilis in HIV pre-exposure prophylaxis users
Authors: Pedrosa Nathália Lima , Pinheiro Patrícia Matias , Filho Fernando Wagner Brito Hortêncio , de Araujo Wildo Navegantes 
Published: April 2024

AbstractBackgroundAcquired syphilis continues to affect millions of people around the world. It is crucial to study it in the context of HIV Pre-Exposure Prophylaxis (PrEP) to achieve the goals set out in the 2030 Agenda since the literature suggests increased risk behaviors for sexually transmitted infections. This study aimed to investigate the incidence and factors associated with acquired syphilis among PrEP users.Materials and methodsThis retrospective cohort included data on PrEP users from all over Brazil from 2018 to 2020, obtained from the national antiretroviral logistics system. We calculated the proportion of syphilis before PrEP, the incidence during the user’s follow-up, reinfections, and their possible associated factors. We conducted descriptive, bivariate, and multivariate analysis, estimating the crude Relative Risk, adjusted Odds Ratio (aOR), and their respective confidence intervals (95%CI).ResultsMost of the 34,000 individuals who started PrEP were male (89.0%), white (53.7%), self-identified as male (85.2%), homosexual, gay, or lesbian (72.2%), and had 12 schooling years or more (67.8%). Of these, 8.3% had syphilis in the six months before starting PrEP, and 4% had it in the first 30 days of using the prophylaxis. In the 19,820 individuals effectively monitored, the incidence of acquired syphilis was 19.1 cases per 100 person-years, and 1.9% of users had reinfection. The multivariate analysis identified female gender (aOR 0.3; 95%CI 0.2-0.5), being white or Black (aOR 0.9; 95%CI 0.7-0.9 and aOR 0.7; 95%CI 0.7-0.99, respectively) as protective factors for syphilis. Being homosexual, gay, lesbian (aOR 2.7; 95%CI 2.0-3.7) or having a history of syphilis in the six months before PrEP (aOR 2.2; 95%CI 1.9-2.5) were risk factors for syphilis during PrEP use. Behaviors related to the risk of syphilis included accepting something in exchange for sex (aOR 1.6; 95%CI 1.3-1.9), irregular condom use (use in less than half of sexual intercourse sessions; aOR 1.7; 95%CI 1.53-2.1) and recreational drug use (poppers; aOR 1.5; 95%CI 1.53-2.1).ConclusionSyphilis in the context of PrEP has high rates and is associated with sociodemographic and behavioral factors. We recommend additional studies targeting prevention in this population to curb these figures.
Pace of Aging in older adults matters for healthspan and lifespan
Authors: Balachandran A , Pei H , Shi Y , Beard J , Caspi A , Cohen A , Domingue BW , Eckstein Indik C , Ferrucci L , Furuya A , Kothari M , Moffitt TE , Ryan C , Skirbekk V , Zhang Y , Belsky DW 
Published: April 2024

ABSTRACTAs societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal care and nutrition, from those caused by ongoing changes in people’s bodies due to aging. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in data from the US Health and Retirement Study and English Longitudinal Study of Aging (N=21,463), integrates longitudinal data on blood biomarkers, physical measurements, and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability, and mortality. Pace of Aging can advance the population science of healthy longevity.
Accurate spatial quantification in computational pathology with multiple instance learning
Authors: Gao Zeyu , Mao Anyu , Dong Yuxing , Wu Jialun , Liu Jiashuai , Wang ChunBao , He Kai , Gong Tieliang , Li Chen , Crispin-Ortuzar Mireia 
Published: April 2024

AbstractSpatial quantification is a critical step in most computational pathology tasks, from guiding pathologists to areas of clinical interest to discovering tissue phenotypes behind novel biomarkers. To circumvent the need for manual annotations, modern computational pathology methods have favoured multiple-instance learning approaches that can accurately predict whole-slide image labels, albeit at the expense of losing their spatial awareness. We prove mathematically that a model using instance-level aggregation could achieve superior spatial quantification without compromising on whole-slide image prediction performance. We then introduce a superpatch-based measurable multiple instance learning method, SMMILe, and evaluate it across 6 cancer types, 3 highly diverse classification tasks, and 8 datasets involving 3,850 whole-slide images. We benchmark SMMILe against 9 existing methods, and show that in all cases SMMILe matches or exceeds state-of-the-art whole-slide image classification performance while simultaneously achieving outstanding spatial quantification.
Cohort profile: the Johns Hopkins COVID Long Study (JHCLS), a United States Nationwide Prospective Cohort Study
Authors: Wentz Eryka , Ni Zhanmo , Yenokyan Karine , Vergara Candelaria , Pahwa Jessica , Kammerling Thea , Xiao Pu , Duggal Priya , Lau Bryan , Mehta Shruti H. 
Published: April 2024

ABSTRACTPurposeCOVID-19 disease continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short- and long-term consequences of COVID-19 disease in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey.ParticipantsSixteen thousand, seven hundred sixty-four adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey.Findings to dateThis cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16,764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported a hospitalization, and 63% were defined as having long COVID using the WHO definition.Future plansAnalysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.
MOSAIC enablesin situsaturation mutagenesis of genes and CRISPR prime editing guide RNA optimization in human cells
Authors: Hsu Jonathan Y. , Lam Kin Chung , Shih Justine , Pinello Luca , Joung J. Keith 
Published: April 2024

AbstractCRISPR prime editing offers unprecedented versatility and precision for the installation of genetic editsin situ. Here we describe the development and characterization of the Multiplexing Of Site-specific Alterations forIn situCharacterization (MOSAIC) method, which leverages a non-viral PCR-based prime editing method to enable rapid installation of thousands of defined edits in pooled fashion. We show that MOSAIC can be applied to performin situsaturation mutagenesis screens of: (1) theBCR-ABL1fusion gene, successfully identifying known and potentially new imatinib drug-resistance variants; and (2) theIRF1untranslated region (UTR), re-confirming non-coding regulatory elements involved in transcriptional initiation. Furthermore, we deployed MOSAIC to enable high-throughput, pooled screening of hundreds of systematically designed prime editing guide RNA (pegRNA) constructs for a large series of different genomic loci. This rapid screening of >18,000 pegRNA designs identified optimized pegRNAs for 89 different genomic target modifications and revealed the lack of simple predictive rules for pegRNA design, reinforcing the need for experimental optimization now greatly simplified and enabled by MOSAIC. We envision that MOSAIC will accelerate and facilitate the application of CRISPR prime editing for a wide range of high-throughput screens in human and other cell systems.
Detection of tomato brown rugose fruit virus in environmental residues: the importance of contextualizing test results
Authors: Giesbers Anne K.J. , Vogel Elise , Skelton Anna , Zisi Zafeiro , Wildhagen Mandy , Loh Yue L. , Ghijselings Lucas , Groothuismink Johanne , Westenberg Marcel , Matthijnssens Jelle , Roenhorst Annelien , Vos Christine , Fox Adrian , Botermans Marleen 
Published: April 2024

AbstractTomato brown rugose fruit virus (ToBRFV) is regulated as a quarantine pest in many countries worldwide. To assess whether ToBRFV is present in cultivations, plants or seed lots, testing is required. The interpretation of test results, however, can be challenging. Real-time RT-PCR results, even though considered “positive”, may not always signify plant infection or indicate the presence of infectious virus, but could be due to the presence of viral residues in the environment. Here, case studies from the Netherlands, Belgium, and the United Kingdom address questions regarding the detection of ToBRFV in various settings, and the infectiousness of ToBRFV positive samples. These exploratory analyses demonstrate widespread detection of ToBRFV in diverse samples and environments. ToBRFV was detected inside and around greenhouses with no prior history of ToBRFV infection, on different materials and surfaces including those that were untouched by individuals, plants, or objects. This suggested the dispersal of viral residues through aerosols. ToBRFV or its residues were more often detected in areas with nearby tomato production yet were also found in a wider environment extending beyond infected crops. Given that ToBRFV originating from environmental contamination may or may not be infectious, adds complexity to decision-making in response to positive test results. Contextual information, such as the origin of the sample and the likelihood of residues from prior cultivations and/or the broader environment, is important for interpreting test results. A nuanced approach is crucial to correctly interpret ToBRFV test results, necessitating further research to support risk assessment.
The transcription factor ZNF469 regulates collagen production in liver fibrosis
Authors: Steinhauser Sebastian , Estoppey David , Buehler Dennis P. , Xiong Yanhua , Pizzato Nicolas , Rietsch Amandine , Wu Fabian , Leroy Nelly , Wunderlin Tiffany , Claerr Isabelle , Tropberger Philipp , Müller Miriam , Davison Lindsay M. , Sheng Quanhu , Bergling Sebastian , Wild Sophia , Moulin Pierre , Liang Jiancong , English Wayne J. , Williams Brandon , Knehr Judith , Altorfer Marc , Reyes Alejandro , Mickanin Craig , Hoepfner Dominic , Nigsch Florian , Frederiksen Mathias , Flynn Charles R. , Fodor Barna D. , Brown Jonathan D. , Kolter Christian 
Published: April 2024

AbstractNon-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world’s population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.
Post-translational cleavage of Mei5 of Dmc1 mediator, Mei5-Sae3 complex, in yeast meiosis
Authors: Mwaniki Stephen , Sawant Priyanka , Osemwenkhae Osaretin P. , Fujita Yurika , Ito Masaru , Furukohri Asako , Shinohara Akira 
Published: April 2024

AbstractInterhomolog recombination in meiosis is mediated by the Dmc1 recombinase. The Mei5-Sae3 complex ofS. cerevisiaepromotes Dmc1 assembly and functions with Dmc1 for homology-mediated repair of meiotic DNA double-strand breaks. How Mei5-Sae3 facilitates Dmc1 assembly remains poorly understood. In this study, we created and characterized severalmei5mutants featuring the amino acid substitutions of basic residues. We found that Arg97 of Mei5, conserved in its ortholog, SFR1(complex with SWI5), RAD51 mediator, in humans and other organisms, is critical for complex formation with Sae3 for Dmc1 assembly. Moreover, the substitution of Arg117 with Ala in Mei5 resulted in the production of a C-terminal truncated Mei5 protein during yeast meiosis. Notably, the shorter Mei5-R117A protein was observed in meiotic cells but not in mitotic cells when expressed, suggesting a unique regulation of Dmc1-mediated recombination by post-translational processing of Mei5-Sae3.
Digital technology uses, purposes, barriers and training programs for culturally and linguistically diverse older adults: a systematic scoping review
Authors: Cunningham Teagan , Murray Carolyn , Du Jia Tina , Evans Nina , Ziaian Tahereh 
Published: April 2024

PurposeThis scoping review article aimed to systematically search the literature on the use, purpose and barriers of information and communication technology (ICT) for culturally and linguistically diverse (CALD) older adults in the host country. The review also conducted a search for literature on programs that aim to develop digital literacy skills for CALD older adults.Design/methodology/approachA scoping review approach was utilized to identify and search the available literature, and to map the key concepts. A total of 23 relevant articles were included following a systematic search across seven databases.FindingsThe review suggests that CALD older adults use ICT for various purposes, including social interaction, health management, information gathering, immigration, everyday routines and leisure. The barriers faced by these older adults in using ICT encompass fear and limited knowledge, language issues, lack of interest, limited access to technology and health concerns. The existing training programs focus on enhancing self-efficacy and confidence and promoting attitudinal changes toward ICT.Originality/valueDespite the presence of empirical studies, few scoping or systematic reviews have focused on CALD older adults and technology. Research developments related to the technology use of CALD older adults and associated training programs have been fragmented and sporadic, resulting in gaps in the evidence base. This review fills such a gap to better understand the research status connected to CALD older people’s technology adoption and use.