bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal typing of molecular HIV clusters in a statewide epidemic
Authors: Novitsky Vlad , Steingrimsson Jon , Howison Mark , Dunn Casey , Gillani Fizza S. , Manne Akarsh , Li Yuanning , Spence Matthew , Parillo Zoanne , Fulton John , Marak Theodore , Chan Philip , Bertrand Thomas , Bandy Utpala , Alexander-Scott Nicole , Hogan Joseph , Kantor Rami 
Published: May 2021

Background:
HIV molecular epidemiology is increasingly integrated into public health prevention. We conducted cluster typing to enhance characterization of a densely sampled statewide epidemic towards informing public health.

Methods:
We identified HIV clusters, categorized them into types, and evaluated their dynamics between 2004 and 2019 in Rhode Island. We grouped sequences by diagnosis year, assessed cluster changes between paired phylogenies, t
0 and t
1, representing adjacent years and categorized clusters as stable (cluster in t
0 phylogeny = cluster in t
1 phylogeny) or unstable (cluster in t
0 ≠ cluster in t
1). Unstable clusters were further categorized as emerging (t
1 phylogeny only) or growing (larger in t
1 phylogeny). We determined proportions of each cluster type, of individuals in each cluster type, and of newly diagnosed individuals in each cluster type, and assessed trends over time.

Results:
A total of 1727 individuals with available HIV-1 subtype B pol sequences were diagnosed in Rhode Island by 2019. Over time, stable clusters and individuals in them dominated the epidemic, increasing over time, with reciprocally decreasing unstable clusters and individuals in them. Conversely, proportions of newly diagnosed individuals in unstable clusters significantly increased. Within unstable clusters, proportions of emerging clusters and of individuals in them declined; whereas proportions of newly diagnosed individuals in growing clusters significantly increased over time.

Conclusion:
Distinct molecular cluster types were identified in the Rhode Island epidemic. Cluster dynamics demonstrated increasing stable and decreasing unstable clusters driven by growing, rather than emerging clusters, suggesting consistent in-state transmission networks. Cluster typing could inform public health beyond conventional approaches and direct interventions.
False-Positive Uptake in Splenic Hemangioma on 68Ga-PSMA PET/CT Scan for Late Biochemical Recurrence of Prostate Cancer
Authors: Brazão Éder Silveira , Ribeiro André Marcondes Braga , Lima Eduardo Nobrega Pereira , da Costa Walter Henriques , Zequi Stênio de Cássio 
Published: May 2021

Abstract
A 71-year-old man underwent 68Ga-PSMA PET/CT for evaluation of a late biochemical recurrence after radical prostatectomy. An intense PSMA uptake was identified in spleen. Additional evaluation with a contrast-enhanced MRI showed a splenic lesion consistent with splenic hemangioma.
Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Surgically Treated Stage I Lung Adenocarcinoma Patients
Authors: Tosi Davide , Pieropan Sara , Cattoni Maria , Bonitta Gianluca , Franzi Sara , Mendogni Paolo , Imperatori Andrea , Rotolo Nicola , Castellani Massimo , Cuzzocrea Marco , Schiorlin Ilaria , Casagrande Sabrina , De Palma Diego , Nosotti Mario , Dominioni Lorenzo 
Published: May 2021

Purpose of the Report
This article aims to explore the prognostic role of 18F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients.

Patients and Methods
One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUVmean and MTV were calculated using SUV threshold of 41% of SUVmax; the total lesion glycolysis (TLG) was calculated as the product of SUVmean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUVmean, 9.6 for SUVmax, and 19.1 for TLG).

Results
Our main finding was the significant correlation between 18F-FDG PET/CT parameters (SUVmean, SUVmax, and TLG) and disease-free survival in pathologic stage I non–small cell lung cancer. SUVmean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689–0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUVmean ≤6.5, SUVmax ≤9.6, and TLG ≤19.1.

Conclusions
Our research supports the hypothesis that SUVmean, SUVmax, and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.
68Ga-FAPI PET/CT Versus 18F-FDG PET/CT for Detecting Metastatic Lesions in a Case of Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Fu Hao , Fu Jie , Huang Jingxiong , Pang Yizhen , Chen Haojun 
Published: May 2021

Abstract

18F-FDG PET/CT is a useful imaging modality for detecting disease recurrence and metastases in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). However, the sensitivity of 18F-FDG PET/CT in RAIR-DTC is not very satisfactory. 68Ga-FAPI is a promising PET tracer that allowed imaging of various types of cancer. In this case, 68Ga-FAPI showed a far better signal-to-background ratio than 18F-FDG for detecting the RAIR-DTC metastatic lesions, especially for detecting the small pulmonary metastases. Therefore, 68Ga-FAPI may be a promising alternative to 18F-FDG for detecting tumor recurrence and metastases in RAIR-DTC. It could also be used for guiding FAP-targeted radionuclide therapy.
Geographic Distribution of Cytomegalovirus Serology in Kidney and Pancreas Transplant Recipients in the United States
Authors: Jorgenson Margaret R. , Parajuli Sandesh , Marka Nicholas , Leverson Glen E. , Smith Jeannina A. , Mandelbrot Didier A. , Odorico Jon S. 
Published: May 2021

Backgrounds.
Cytomegalovirus (CMV) negatively affects transplant outcomes. The current geographic distribution of CMV risk within the US has not been described.

Methods.
CMV serostatus of donors and recipients in each US state were collected from the Scientific Registry of Transplant Recipients between April 1, 2015, and March 31, 2019. The objective was to describe rates of CMV recipient seropositivity (R+) and high-risk serostatus (D+/R−) across the US in kidney transplant recipient (KTR) and pancreas transplant recipient (PTR) and explore geographic disparities.

Results.
A total of 79 276 KTRs and 4023 PTRs were included. The average KTR R+ rate across states was 59.5% (range 39%–76%); PTR R+ rate was 49.5% but with a broader range (0%–100%). The average KTR D+/R− rate across the US was 19% (range 8.7%–25%); PTR D+/R− rate was notably higher (26.9%, range 0%–50%). KTR seropositivity varied geographically with more R+ recipients in the southern states, Alaska, and Hawaii. D+/R− KTRs also varied by region, with higher rates in the Rocky Mountain Region as well as the Midwest and the northern-most states of the Northeast. Trends found in KTR persisted in PTR.

Conclusions.
The distribution of CMV serostatus in the US varies by state and allograft type. These data may be useful in further discussion of national CMV donor-matching strategies.
Donor-derived Cell-free DNA Kinetics Post-kidney Transplant Biopsy
Authors: Kyeso Yousuf , Bhalla Anshul , Smith Alyssa P. , Jia Yaqi , Alakhdhair Safa , Ogir Stephanie C. , Abuzeineh Mohammad , Brennan Daniel C. , Alasfar Sami 
Published: May 2021

Background.
Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney injury including transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the postbiopsy period. We evaluated the effect of KT biopsy on the kinetics of dd-cfDNA.

Methods.
We conducted a single-arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within 8 h before the biopsy (prebiopsy), within 20 min (hour 0), 2 h (hour 2), and 24–48 h (hours 24–48) after the biopsy. We evaluated the change in dd-cfDNA from the prebiopsy time point to the following 3 time points after the biopsy.

Results.
At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate 0.4 [0.17-0.63] and 0.39 [0.09-0.68], respectively). By 24–28 h postbiopsy, there was no significant difference in log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate −0.21 [−0.6 to 0.19]).

Conclusions.
Mechanical injury from a KT biopsy can transiently increase circulating dd-cfDNA. The increase resolves by 24–48 h after the biopsy. Providers should wait 48 h postbiopsy to obtain dd-cfDNA levels to establish the correct baseline to be used for monitoring.
Clinical Care and Unmet Needs of Individuals With Dementia With Lewy Bodies and Caregivers
Authors: Armstrong Melissa J. , Gamez Noheli , Alliance Slande , Majid Tabassum , Taylor Angela S. , Kurasz Andrea M. , Patel Bhavana , Smith Glenn E. 
Published: May 2021

Background:
Patient-centered care requires understanding patient preferences and needs, but research on the clinical care preferences of individuals living with dementia and caregivers is sparse, particularly in dementia with Lewy bodies (DLB).

Methods:
Investigators conducted telephone interviews with individuals living with DLB and caregivers from a Lewy body dementia specialty center. Interviews employed a semistructured questionnaire querying helpful aspects of care and unmet needs. Investigators used a qualitative descriptive approach to analyze transcripts and identify themes.

Results:
Twenty individuals with DLB and 25 caregivers participated. Twenty-three of the caregivers were spouses, 2 were daughters. Aspects of clinical care valued by individuals with DLB and caregivers included clinician time, diagnosis, education, symptom management, communication, and caring staff. Unmet needs or challenges included patient/caregiver education, education of nonspecialist clinicians and community care providers, scheduling difficulties, caregiver support, financial concerns, assistance with advance care planning and finding local resources, and effective treatments for DLB symptoms.

Conclusion and Relevance:
Improving care for individuals with DLB and their families will require a multipronged strategy including education for nonspecialist care providers, increasing specialty care access, improved clinical care services, research to support disease prognosis and treatment decisions, and local and national strategies for enhanced caregiver support.
COVID-19 County Level Severity Classification with Imbalanced Dataset: A NearMiss Under-sampling Approach
Authors: Oladunni Timothy , Tossou Sourou , Haile Yayehyrad , Kidane Adonias 
Published: May 2021

AbstractCOVID-19 pandemic that broke out in the late 2019 has spread across the globe. The disease has infected millions of people. Thousands of lives have been lost. The momentum of the disease has been slowed by the introduction of vaccine; however, some countries are still recording high number of casualties. The focus of this work is to design, develop and evaluate a machine learning county level COVID-19 severity classifier. The proposed model will predict severity of the pandemic in a county into low, moderate, or high. Policy makers will find the work useful in the distribution of vaccines. Four learning algorithms (two ensembles and two non-ensembles) were trained and evaluated. Class imbalance was addressed using NearMiss under-sampling of the majority classes. The result of our experiment shows that the ensemble models outperformed the non-ensemble models by a considerable margin.
Transcriptional overlap links DNA hypomethylation with DNA hypermethylation at adjacent promoters in cancer
Authors: Fain Jean , Loriot Axelle , Diacofotaki Anna , Van Tongelen Aurélie , De Smet Charles 
Published: May 2021

ABSTRACTDNA methylation is an epigenetic mark associated with gene repression. It is now well established that tumor development involves alterations in DNA methylation patterns, which include both gains (hypermethylation) and losses (hypomethylation) of methylation marks in different genomic regions. The mechanisms underlying these two opposite, yet co-existing, alterations in tumors remain unclear. While studying the human MAGEA6/GABRA3 gene locus, we observed that DNA hypomethylation in tumor cells can lead to the activation of a long transcript (CT-GABRA3) that overlaps downstream promoters (GABRQ and GABRA3) and triggers their hypermethylation. Overlapped promoters displayed increases in H3K36me3, a histone mark known to be deposited during progression of the transcription machinery and to stimulate de novo DNA methylation. Consistent with such a processive mechanism, increases in H3K36me3 and DNA methylation were observed over the entire region covered by the CT-GABRA3 overlapping transcript. Importantly, experimental induction of CT-GABRA3 by depletion of DNMT1 DNA methyltransferase, resulted in a similar pattern of increased DNA methylation in the MAGEA6/GABRA3 locus. Bioinformatics analyses in lung cancer datasets identified other genomic loci displaying this process of coupled DNA hypo- and hypermethylation. In several of these loci, DNA hypermethylation affected tumor suppressor genes, e.g. RERG and PTPRO. Together, our work reveals that focal DNA hypomethylation in tumors can indirectly contribute to hypermethylation of nearby promoters through activation of overlapping transcription, and establishes therefore an unsuspected connection between these two opposite epigenetic alterations.
Age- and airway disease related gene expression patterns of key SARS-CoV-2 entry factors in human nasal epithelia
Authors: Plaas Mihkel , Seppa Kadri , Gaur Nayana , Kasenõmm Priit , Plaas Mario 
Published: May 2021

AbstractThe global COVID-19 pandemic caused by SARS-CoV-2 predominantly affects the elderly. Differential expression of SARS-CoV-2 entry genes may underlie the variable susceptibility in different patient groups. Here, we examined the gene expression of key SARS-CoV-2 entry factors in mucosal biopsies to delineate the roles of age and existing chronic airway disease. A significant inverse correlation between ACE2 and age and a downregulation of NRP1 in patients with airway disease were noted. These results indicate that the interplay between various factors may influence susceptibility and the disease course.
A comparative study of SIR Model, Linear Regression, Logistic Function and ARIMA Model for forecasting COVID-19 cases
Authors: Abolmaali Saina 
Published: May 2021

AbstractStarting February 2020, COVID-19 was confirmed in 11,946 people worldwide, with a mortality rate of almost 2%. A significant number of epidemic diseases including human Coronavirus display patterns. In this study with the benefit of data analytic, we develop regression models and a Susceptible-Infected-Recovered (SIR) model for the contagion to compare the performance of models to predict number of cases. first, we implement a good understanding of data and perform Exploratory Data Analysis (EDA). Then, we derive the parameters of the model from the available data corresponding to the top 4 regions based on the history of infections and the most infected people as of the end of August 2020. Then models are compared and further research are introduced.
Adaptation to chronic ER stress enforces pancreatic β-cell plasticity
Authors: Chen Chien-Wen , Guan Bo-Jhih , Alzahrani Mohammed R. , Gao Zhaofeng , Gao Long , Bracey Syrena , Haataja Leena , Schaffer Ashleigh E. , Lee Hugo , Laframboise Thomas , Bederman Ilya , Arvan Peter , Mathews Clayton E. , Gerling Ivan C. , Kaestner Klaus H. , Tirosh Boaz , Engin Feyza , Hatzoglou Maria 
Published: May 2021

AbstractPancreatic β-cells undergo high levels of endoplasmic reticulum (ER) stress due to their role in insulin secretion. Hence, they require sustainable and efficient adaptive stress responses to cope with the stress. Whether duration and episodes of chronic ER stress directly compromises β-cell identity is largely unknown. We show that under reversible, chronic ER stress, β-cells undergo a distinct transcriptional and translational reprogramming. During reprogramming, expression of master regulators of β-cell function and identity and proinsulin processing is impaired. Upon recovery from stress, β-cells regain their identity, highlighting a high-degree of adaptive β-cell plasticity. Remarkably, when stress episodes exceed a certain threshold, β-cell identity is gradually lost. Single cell RNA-seq analysis of islets from type 1 diabetes (T1D) patients, identifies the severe deregulation of the chronic stress-adaptation program, and reveals novel biomarkers for progression of T1D. Our results suggest β-cell adaptive exhaustion (βEAR) is a significant component of the pathogenesis of T1D.
Old data and friends improve with age: Advancements with the updated tools of GeneNetwork
Authors: Chunduri Alisha , Ashbrook David G. 
Published: May 2021

AbstractUnderstanding gene-by-environment interactions is important across biology, particularly behaviour. Families of isogenic strains are excellently placed, as the same genome can be tested in multiple environments. The BXD’s recent expansion to 140 strains makes them the largest family of murine isogenic genomes, and therefore give great power to detect QTL. Indefinite reproducible genometypes can be leveraged; old data can be reanalysed with emerging tools to produce novel biological insights.To highlight the importance of reanalyses, we obtained drug- and behavioural-phenotypes from Philipet al.2010, and reanalysed their data with new genotypes from sequencing, and new models (GEMMA and R/qtl2). We discover QTL on chromosomes 3, 5, 9, 11, and 14, not found in the original study.We narrowed down the candidate genes based on their ability to alter gene expression and/or protein function, usingcis-eQTL analysis, and variants predicted to be deleterious. Co-expression analysis (‘gene friends’) and human PheWAS were used to further narrow candidates.Prominent candidate genes include:Slitrk6in a Chr 14 QTL for locomotion in the center of an open field, we show to be part of a coexpression network involved in voluntary movement, and association with neuropsychiatric phenotypes in PheWAS; andCdk14, one of only 3 genes in a Chr 5 QTL for handling induced convulsions after ethanol treatment, that is regulated by the anticonvulsant drug valproic acid.By using families of isogenic strains, we can reuse and reanalyse data to discover novel and highly plausible candidate genes involved in response to the environment.
miRNA-34c suppresses osteosarcoma progression in vivo by targeting Notch and E2F
Authors: Bae Yangjin , Zeng Huan-Chang , Chen Yi-Ting , Ketkar Shamika , Munivez Elda , Yu Zhiyin , Gannon Francis H. , Lee Brendan H. 
Published: May 2021

ABSTRACTThe expression of microRNAs (miRNAs) is dysregulated in many types of cancers including osteosarcoma (OS) due to genetic and epigenetic alterations. Among these, miR-34c, an effector of tumor suppressor P53 and an upstream negative regulator of Notch signaling in osteoblast differentiation, is dysregulated in OS. Here, we demonstrated a tumor suppressive role of miR-34c in OS progression using in vitro assays and in vivo genetic mouse models. We found that miR-34c inhibits the proliferation and the invasion of metastatic OS cells, which resulted in reduction of the tumor burden and increased overall survival in an orthotopic xenograft model. Moreover, the osteoblast specific over expression of miR-34c increased survival in the osteoblast specific p53 mutant OS mouse model. We found that miR-34c regulates the transcription of several genes in Notch signaling (NOTCH1, JAG1 and HEY2) and in p53 mediated cell cycle and apoptosis (CCNE2, E2F5, E2F2 and HDAC1). More interestingly, we found that the metastatic free survival probability was increased among a patient cohort from TARGET OS which has lower expression of direct targets of miR-34c that was identified in our transcriptome analysis such as E2F5 and NOTCH1. In conclusion, we demonstrate that miR-34c is a tumor suppressive miRNA in OS progression in vivo. In addition, we highlight the therapeutic potential of targeting miR-34c in OS.
Multiple Causal Variants Underlie Genetic Associations in Humans
Authors: Abell Nathan S. , DeGorter Marianne K. , Gloudemans Michael , Greenwald Emily , Smith Kevin S. , He Zihuai , Montgomery Stephen B. 
Published: May 2021

ABSTRACTThe majority of associations between genetic variation and human traits and diseases are non-coding and in strong linkage disequilibrium (LD) with surrounding genetic variation. In these cases, a single causal variant is often assumed to underlie the association, however no systematic assessment of the number of causal variants has been performed. In this study, we applied a massively parallel reporter assay (MPRA) in lymphoblastoid cells to functionally evaluate 49,256 allelic pairs, representing 30,893 genetic variants in high, local linkage disequilibrium for 744 independent cis-expression quantitative trait loci (eQTL) and assessed each for colocalization across 114 traits. We identified 8,502 allele-independent regulatory regions containing 1,264 allele-specific regulatory variants, and found that 17.7% of eQTL contained more than one significant allelic effect. We show that detected regulatory variants are highly and specifically enriched for activating chromatin structures and allelic transcription factor binding, for which ETS-domain family members are a large driver. Integration of MPRA profiles with eQTL/complex trait colocalizations identified causal variant sets for associations with blood cell measurements, Asthma, Multiple Sclerosis, Inflammatory Bowel Disease, and Crohn’s Disease. These results demonstrate that a sizable number of association signals are manifest through multiple, tightly-linked causal variants requiring high-throughput functional assays for fine-mapping.
On the sparsity of fitness functions and implications for learning
Authors: Brookes David H. , Aghazadeh Amirali , Listgarten Jennifer 
Published: May 2021

AbstractFitness functions map biological sequences to a scalar property of interest. Accurate estimation of these functions yields biological insight and sets the foundation for model-based sequence design. However, the amount of fitness data available to learn these functions is typically small relative to the large combinatorial space of sequences; characterizing how much data is needed for accurate estimation remains an open problem. There is a growing body of evidence demonstrating that empirical fitness functions display substantial sparsity when represented in terms of epistatic interactions. Moreover, the theory of Compressed Sensing provides scaling laws for the number of samples required to exactly recover a sparse function. Motivated by these results, we develop a framework to study the sparsity of fitness functions sampled from a generalization of the NK model, a widely-used random field model of fitness functions. In particular, we present results that allow us to test the effect of the Generalized NK (GNK) model’s interpretable parameters—sequence length, alphabet size, and assumed interactions between sequence positions—on the sparsity of fitness functions sampled from the model and, consequently, the number of measurements required to exactly recover these functions. We validate our framework by demonstrating that GNK models with parameters set according to structural considerations can be used to accurately approximate the number of samples required to recover two empirical protein fitness functions and an RNA fitness function. In addition, we show that these GNK models identify important higher-order epistatic interactions in the empirical fitness functions using only structural information.