bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303
Authors: Russler-Germain David A. , Krysiak Kilannin , Ramirez Cody , Mosior Matthew , Watkins Marcus P. , Gomez Felicia , Skidmore Zachary L. , Trani Lee , Gao Feng , Geyer Susan , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Bartlett Nancy L. , Alderuccio Juan P. , Lossos Izidore S. , Ondrejka Sarah L. , Hsi Eric D. , Martin Peter , Leonard John P. , Griffith Malachi , Griffith Obi L. , Fehniger Todd A. 
Published: July 2023

Abstract
Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7–Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients.
Plasmodium falciparum infection of human erythroblasts induces transcriptional changes associated with dyserythropoiesis
Authors: Feldman Tamar P. , Ryan Yana , Egan Elizabeth S. 
Published: July 2023

Abstract
During development down the erythroid lineage, hematopoietic stem cells undergo dramatic changes to cellular morphology and function in response to a complex and tightly regulated program of gene expression. In malaria infection, Plasmodium spp parasites accumulate in the bone marrow parenchyma, and emerging evidence suggests erythroblastic islands are a protective site for parasite development into gametocytes. Although it has been observed that Plasmodium falciparum infection in late-stage erythroblasts can delay terminal erythroid differentiation and enucleation, the mechanism(s) underlying this phenomenon are unknown. Here, we apply RNA sequencing after fluorescence-activated cell sorting of infected erythroblasts to identify transcriptional responses to direct and indirect interaction with P falciparum. Four developmental stages of erythroid cells were analyzed: proerythroblast, basophilic erythroblast, polychromatic erythroblast, and orthochromatic erythroblast. We found extensive transcriptional changes in infected erythroblasts compared with that in uninfected cells in the same culture, including dysregulation of genes involved in erythroid proliferation and developmental processes. Although some indicators of cellular oxidative and proteotoxic stress were common across all stages of erythropoiesis, many responses were specific to cellular processes associated with developmental stage. Together, our results evidence multiple possible avenues by which parasite infection can induce dyserythropoiesis at specific points along the erythroid continuum, advancing our understanding of the molecular determinants of malaria anemia.
A critical interpretive synthesis of the lived experiences and health and patient-reported outcomes of people living with COPD who isolated during the COVID-19 pandemic
Authors: Swain Rose , Forsyth Faye , Bowers Ben , Early Frances , Kuhn Isla , Shrivastva Sagar , Tufnell Rachel , Fuld Jonathan 
Published: July 2023

Aims:To determine the lived experiences of people with COPD who isolated at home during the coronavirus disease 2019 (COVID-19) pandemic, and explore how these experiences affected health and patient-reported outcomes.Methods:Keyword searches were performed in five bibliographic databases. Critical interpretative synthesis (CIS) methods were used to interrogate and understand patterns across studies.Results:23 studies were identified; three employed qualitative methods and 20 quantitative methods. Application of CIS methods highlighted a core synthetic concept that appeared to underpin experiences and outcomes, that of a heightened perception of risk. Using the Risk Perception Model as a framework, we found that cognitive factors such as knowledge of underlying health status and the transmissibility of COVID-19; experiential factors including previous episodes of breathlessness and hospitalisation; and sociocultural factors such as access to trusted sources of information, influenced perceptions of risk. In turn, this influenced behaviour, which translated to outcomes such as reduced hospitalisations, deconditioning and social isolation as people avoided “high-risk” situations and settings.Conclusions:Patients with COPD who isolated at home during the COVID-19 pandemic had a heightened perception of risk which was influenced by cognitive, experiential and sociocultural factors. The consequences of this were varied and included both positive (reduced exacerbations and hospitalisations) and negative (social isolation, deconditioning, diminished capacity for self-care) outcomes. Understanding risk and the impacts it can have could help clinicians to support people with COPD return to their pre-pandemic way of living and enable better communication of ongoing risk from respiratory viral illness.
RGA1 Negatively Regulates Thermo-tolerance by Affecting Carbohydrate Metabolism and the Energy Supply in Rice
Authors: Feng Baohua , Xu Yongqiang , Fu Weimeng , Li Hubo , Li Gengmi , Li Juncai , Wang Wenting , Tao Longxing , Chen Tingting , Fu Guanfu 
Published: July 2023

AbstractBackgroundSignal transduction mediated by heterotrimeric G proteins, which comprise the α, β, and γ subunits, is one of the most important signaling pathways in rice plants.RGA1, which encodes the Gα subunit of the G protein, plays an important role in the response to various types of abiotic stress, including salt, drought, and cold stress. However, the role ofRGA1in the response to heat stress remains unclear.ResultsThe heat-resistant mutantett1(enhanced thermo-tolerance 1) with a new allele of theRGA1gene was derived from an ethane methyl sulfonate-induced Zhonghua11 mutant. After 45 °C heat stress treatment for 36 h and recovery for 7 d, the survival rate of theett1mutants was significantly higher than that of wild-type (WT) plants. The malondialdehyde content was lower, and the maximum fluorescence quantum yield of photosystem II, peroxidase activity, andhspexpression were higher inett1mutants than in WT plants after 12 h of exposure to 45 °C. The RNA-sequencing results revealed that the expression of genes involved in the metabolism of carbohydrate, nicotinamide adenine dinucleotide, and energy was up-regulated inett1under heat stress. The carbohydrate content and the relative expression of genes involved in sucrose metabolism indicated that carbohydrate metabolism was accelerated inett1under heat stress. Energy parameters, including the adenosine triphosphate (ATP) content and the energy charge, were significantly higher in theett1mutants than in WT plants under heat stress. Importantly, exogenous glucose can alleviate the damages on rice seedling plants caused by heat stress.ConclusionRGA1negatively regulates the thermo-tolerance in rice seedling plants through affecting carbohydrate and energy metabolism.
A high-throughput screening system for SARS-CoV-2 entry inhibition, syncytia formation and cell toxicity
Authors: Jancy Shine Varghese , Lupitha Santhik Subhasingh , Chandrasekharan Aneesh , Varadarajan Shankara Narayanan , Nelson-Sathi Shijulal , Prasad Roshny , Jones Sara , Easwaran Sreekumar , Darvin Pramod , Sivasailam Aswathy , Santhoshkumar Thankayyan Retnabai 
Published: July 2023

Abstract
Background
The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is mediated through the binding of the SARS-CoV-2 Spike protein via the receptor binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2). Identifying compounds that inhibit Spike-ACE2 binding would be a promising and safe antiviral approach against COVID-19.

Methods
In this study, we used a BSL-2 compatible replication-competent vesicular stomatitis virus (VSV) expressing Spike protein of SARS-CoV-2 with eGFP reporter system (VSV-eGFP-SARS-CoV-2) in a recombinant permissive cell system for high-throughput screening of viral entry blockers. The SARS-CoV-2 permissive reporter system encompasses cells that stably express hACE2-tagged cerulean and H2B tagged with mCherry, as a marker of nuclear condensation, which also enables imaging of fused cells among infected EGFP positive cells and could provide real-time information on syncytia formation.

Results
A limited high-throughput screening identified six natural products that markedly inhibited VSV-eGFP-SARS-CoV-2 with minimum toxicity. Further studies of Spike-S1 binding using the permissive cells showed Scillaren A and 17-Aminodemethoxygeldanamycin could inhibit S1 binding to ACE2 among the six leads. A real-time imaging revealed delayed inhibition of syncytia by Scillaren A, Proscillaridin, Acetoxycycloheximide and complete inhibition by Didemnin B indicating that the assay is a reliable platform for any image-based drug screening.

Conclusion
A BSL-2 compatible assay system that is equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effects on syncytia. Studies using clinical isolates of SARS-CoV-2 are warranted to confirm the antiviral potency of the leads and the utility of the screening system.
OGRE: calculate, visualize, and analyze overlap between genomic input regions and public annotations
Authors: Berres Sven , Gromoll Jörg , Wöste Marius , Sandmann Sarah , Laurentino Sandra 
Published: July 2023

Abstract
Background
Modern genome sequencing leads to an ever-growing collection of genomic annotations. Combining these elements with a set of input regions (e.g. genes) would yield new insights in genomic associations, such as those involved in gene regulation. The required data are scattered across different databases making a manual approach tiresome, unpractical, and prone to error. Semi-automatic approaches require programming skills in data parsing, processing, overlap calculation, and visualization, which most biomedical researchers lack. Our aim was to develop an automated tool providing all necessary algorithms, benefiting both bioinformaticians and researchers without bioinformatic training.

Results
We developed overlapping annotated genomic regions (OGRE) as a comprehensive tool to associate and visualize input regions with genomic annotations. It does so by parsing regions of interest, mining publicly available annotations, and calculating possible overlaps between them. The user can thus identify location, type, and number of associated regulatory elements. Results are presented as easy to understand visualizations and result tables. We applied OGRE to recent studies and could show high reproducibility and potential new insights. To demonstrate OGRE’s performance in terms of running time and output, we have conducted a benchmark and compared its features with similar tools.

Conclusions
OGRE’s functions and built-in annotations can be applied as a downstream overlap association step, which is compatible with most genomic sequencing outputs, and can thus enrich pre-existing analyses pipelines. Compared to similar tools, OGRE shows competitive performance, offers additional features, and has been successfully applied to two recent studies. Overall, OGRE addresses the lack of tools for automatic analysis, local genomic overlap calculation, and visualization by providing an easy to use, end-to-end solution for both biologists and computational scientists.
Multiple refractory intracellular pathogen infections in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibodies: a case report
Authors: Wang Hongxia , Lei Rong , Ji Yang , Xu Wei , Zhang Keke , Guo Xiang 
Published: July 2023

Abstract
Background
The clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease.

Case presentation
We report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient’s serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient’s symptoms, pulmonary lesions, and bone destruction gradually improved.

Conclusions
Although the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections.
Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.
The joint effect of gestational diabetes mellitus and hypertension contribute to higher risk of diabetes mellitus after delivery: a nationwide population-based study
Authors: Kek Ho-Poh , Su Yu-Tsun , Tey Shu-Jiin , Yang Ming-Chun , Chang Li-Ching , Hung Yun-Hsiang , Tsai Ching-Chung 
Published: July 2023

Abstract
Background
Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) are known risk factors for postpartum diabetes mellitus (DM) and hypertension, respectively. This study aimed to examine the association between the co-occurrence of GDM and PIH and the subsequent development of diabetes mellitus (DM), hypertension, and metabolic syndrome.

Methods
A cohort study was conducted using data from the Taiwan National Health Insurance Research Database (TNHIRD). The study population included 2,297,613 pregnant women with no history of certain medical conditions who gave birth between 2004 and 2015. The women were classified into four cohorts based on their medical history: GDM cohort, PIH cohort, both GDM and PIH cohort, and normal cohort (without GDM and PIH).

Results
The GDM cohort had a higher risk of developing DM, hypertension, and metabolic syndrome than the normal cohort, with hazard ratios of 7.07, 1.54, and 2.51, respectively. The PIH cohort also had an increased risk for these conditions compared with the normal cohort, with hazard ratios of 3.41, 7.26, and 2.68, respectively. The cohort with both GDM and PIH had the highest risk of developing postpartum DM, hypertension, and metabolic syndrome, with hazard ratios of 21.47, 8.02, and 5.04, respectively, compared with the normal cohort.

Conclusion
The cohort of patients with both GDM and PIH had the highest impact on developing postpartum DM compared with either condition alone cohort. Furthermore, the co-occurrence of both conditions increases the risk, with a higher likelihood of developing postpartum DM than hypertension or metabolic syndrome.
Impact of COVID-19 control on lung, breast, and colorectal pathological cancer diagnoses. A comparison between the Netherlands, Aotearoa New Zealand, and Northern Ireland
Authors: Mitchell Helen , Mclean Jennifer , Gavin Anna T , Visser Otto , Millar Elinor , Luff Tessa , Bennett Damien 
Published: July 2023

Abstract
Background
The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries.

Method
Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017–2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population.

Results
Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%).

Conclusion
The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat ‘missing’ patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.
Sociocultural and structural influences on HIV Pre-Exposure Prophylaxis (PrEP) Engagement and Uptake among African American Young adults
Authors: Ayangeakaa Suur D. , Kerr Jelani , Combs Ryan M. , Harris Lesley M. , Sears Jeanelle S. , Parker Kimberly , Sterrett-Hong Emma 
Published: July 2023

Abstract
Background
Pre-exposure prophylaxis (PrEP) demonstrates effectiveness in decreasing new cases of HIV. However, few African Americans use PrEP, despite being disproportionately impacted by HIV. Understanding the influence of sociocultural and structural factors on PrEP use among multiple priority groups of African Americans, including but not limited to men who have sex with men, may improve PrEP engagement and uptake. The social ecological model (SEM) as a framework guided the understanding of how these factors operate on multiple levels to influence PrEP use among this population.

Methods
This study derived data from the Afya PrEP study consisting of eleven focus groups (N = 63) with 18-29-year-old African American sexual and gender minority and heterosexual individuals at heightened behavioral vulnerability to HIV. We employed constructivist grounded theory processes to inductively analyze the data. A pooled kappa score of 0.90 indicated excellent inter-rater agreement.

Results
Factors impacting PrEP engagement among African American young adults included: (1) Community/social network influences; (2) medical mistrust; (3) stigma; (4) PrEP availability and accessibility, which had two sub-categories: (a) cost and (b) where to obtain PrEP; and (5) PrEP engagement strategies, which had two sub-categories: (a) current AIDS service organizations’ PrEP engagement practices and (b) recommended future PrEP engagement strategies. Categories one through three represent sociocultural factors, and categories four and five represent structural factors that influence perceptions and attitudes of African American young adults regarding PrEP.

Conclusion
Our study highlights sociocultural and structural factors that act as barriers and facilitators to PrEP engagement. The SEM guided the understanding of how these factors operated on multiple levels. One of the sociocultural factors, community/social network influences operated at the interpersonal level of the SEM; the other two, stigma and medical mistrust, operated at the community level. The structural factors (PrEP availability, accessibility, and engagement strategies) operated at the institutional/organizational level. Thus, multi-level interventions are warranted to improve PrEP engagement among various African American young adult priority groups.
The underlying molecular mechanisms and biomarkers between periodontitis and COVID-19
Authors: Qin Danlei , Yu Feiyan , Wu Dongchao , Han Chong , Yao Xuemin , Yang Lulu , Yang Xi , Wang Qianqian , He Dongning , Zhao Bin 
Published: July 2023

Abstract
Objective
Emerging evidence shows the clinical consequences of patient with COVID-19 and periodontitis are not promising, and periodontitis is a risk factor. Periodontitis and COVID-19 probably have a relationship. Hence, this study aimed to identify the common molecular mechanism that may help to devise potential therapeutic strategies in the future.

Material and methods
We analyzed two RNA-seq datasets for differential expressed genes, enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types in periodontitis, COVID-19 and healthy controls. Relationships between TFs and mRNA were established by Pearson correlation analysis, and the common TFs-mRNA regulatory network and nine co-upregulated TFs of the two diseases was obtained. The RT-PCR detected the TFs.

Results
A total of 1616 and 10201 differentially expressed gene (DEGs) from periodontitis and COVID-19 are found. Moreover, nine shared TFs and common biological processes associated with lymphocyte activation involved in immune response were identified across periodontitis and COVID-19. The cell type enrichment revealed elevated plasma cells among two diseases. The RT-PCR further confirmed the nine TFs up-regulation in periodontitis.

Conclusion
The pathogenesis of periodontitis and COVID-19 is closely related to the expression of TFs and lymphocyte activation, which can provide potential targets for treatment.