bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Connectivity During the COVID-19 Pandemic: Disparities among Medicare Beneficiaries
Authors: Jacobs Molly , Ellis Charles 
Published: July 2021

Purpose Social connections are essential for health and well-being at all ages and may be especially important for promoting health in later life. Maintaining social connections, however, became increasingly difficult during the COVID-19 pandemic when stay-at-home orders were enacted, and social distancing became necessary. This study examines the social connectivity among Medicare beneficiaries during the COVID-19 pandemic highlighting the importance technological availability, income, and race. Methods Data from the 2020 Medicare Beneficiaries Survey COVID supplement was used to evaluate social connectedness during the spring and fall of 2020. Binomial logistic regression evaluated the relationship between feelings of social connectedness and race/ethnicity, urban status of residence, income, availability of household technologies, internet access, and chronic conditions. Results Lower social connectivity is significantly correlated with race and income. Blacks had a nearly 30% higher likelihood of feeling socially disconnected than other racial groups. Individuals with chronic conditions, particularly cancer, were significantly more likely to feel socially disconnected. Internet access and the availability of technological devices decreased the odds of feeling socially disconnected by 20% and 15% respectively. Conclusion The COVID-19 pandemic decreased the social connectedness of many vulnerable groups specifically Blacks, those living with chronic conditions, and individuals with limited access to technology. While it is outside the scope of the current study, additional research is needed to determine how to address the social and psychological impacts of the COVID-19 pandemic among elderly Americans.
PROMIS Scales for Assessment of Persistent Post-COVID Symptoms: A Cross Sectional Study
Authors: Ganesh Ravindra , Ghosh Aditya K. , Nyman Mark A. , Croghan Ivana T. , Grach Stephanie L. , Anstine Christopher V. , Salonen Bradley R. , Hurt Ryan T. 
Published: July 2021

Objective Persistent post-COVID symptoms are estimated to occur in up to 10% of patients who have had COVID-19. These lingering symptoms may persist for weeks to months after resolution of the acute illness. This study aimed to add insight into our understanding of certain post-acute conditions and clinical findings. The primary purpose was to determine the persistent post COVID impairments prevalence and characteristics by collecting post COVID illness data utilizing Patient-Reported Outcomes Measurement Information System (PROMIS®). The resulting measures were used to assess surveyed patients physical, mental, and social health status. Methods A cross-sectional study and 6-months Mayo Clinic COVID recovered registry data were used to evaluate continuing symptoms severity among the 817 positive tested patients surveyed between March and September 2020. The resulting PROMIS® data set was used to analyze patients post 30 days health status. The e-mailed questionnaires focused on fatigue, sleep, ability to participate in social roles, physical function, and pain. Results The large sample size (n = 817) represented post hospitalized and other managed outpatients. Persistent post COVID impairments prevalence and characteristics were determined to be demographically young (44 years), white (87%), and female (61%). Dysfunction as measured by the PROMIS® scales in patients recovered from acute COVID-19 was reported as significant in the following domains: ability to participate in social roles (43.2%), pain (17.8%), and fatigue (16.2%). Conclusion Patient response on the PROMIS® scales was similar to that seen in multiple other studies which used patient reported symptoms. As a result of this experience, we recommend utilizing standardized scales such as the PROMIS® to obtain comparable data across the patients’ clinical course and define the disease trajectory. This would further allow for effective comparison of data across studies to better define the disease process, risk factors, and assess the impact of future treatments.
Central Sensitization Phenotypes in Post Acute Sequelae of SARS-CoV-2 Infection (PASC): Defining the Post COVID Syndrome
Authors: Bierle Dennis M. , Aakre Christopher A , Grach Stephanie L. , Salonen Bradley R , Croghan Ivana T. , Hurt Ryan T , Ganesh Ravindra 
Published: July 2021

Objective To develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020. Methods A total of 465 patients with a history of testing positive for COVID-19 were identified and their medical records reviewed. After a thorough review, utilizing the DELPHI methods by an expert panel, 42 (9%) cases were identified with persistent central sensitization (CS) symptoms persisting after the resolution of acute COVID-19, herein referred to as Post COVID syndrome (PoCoS). In this report we describe the baseline characteristics of these PoCoS patients. Results Among these 42 PoCoS patients, the mean age was 46.2 years (median age was 46.5 years). Pain (90%), fatigue (74%), dyspnea (43%), and orthostatic intolerance (38%) were the most common symptoms. The characteristics of an initial 14 patients were utilized for the development of clinical criteria via a modified Delphi Method by a panel of experts in central sensitization disorders. These criteria were subsequently applied in the identification of 28 additional cases of suspected PoCoS. A 2-reviewer system was used to analyze agreement with using the criteria, with all 28 cases determined to be either probable or possible cases by the reviewers. Inter-reviewer agreement using these proposed defining criteria was high with a Cohen’s alpha of .88. Conclusions Here we present what we believe to be the first definitional criteria for Post COVID syndrome. These may be useful in clinical phenotyping of these patients for targeted treatment and future research.
Comparison of intramedullary nailing fixation and percutaneous locked plating fixation for the treatment of proximal tibial fractures: A meta-analysis
Authors: Ren Cheng , Li Ming , Sun Liang , Li Zhong , Xu Yibo , Lu Yao , Wang Qian , Ma Teng , Xue Hanzhong , Zhang Kun 
Published: July 2021

Objective: This meta-analysis aimed to systematically compare the clinical outcomes of intramedullary nailing (IMN) fixation and percutaneous locked plating (PLP) fixation in the treatment of proximal tibial fractures. Methods: We searched PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wan Fang to select relevant articles up to March 29, 2020 without language limit. Continuous variables were estimated by weighted mean difference (WMD) with a 95% confidence interval (CI) and dichotomous outcomes were calculated by relative risk (RR) with 95% CI. Moreover, heterogeneity analysis was evaluated. Furthermore, publication bias assessment and sensitivity analysis were conducted. Stata 11.0 software was used to perform the statistical analysis. Results: Ten studies involving 667 cases (321 from IMN fixation group and 346 from PLP fixation group) were included. The type of fractures involved in the included articles was extra-articular proximal tibia fractures. IMN fixation method achieved significantly shorter union time ( WMD = −2.88, 95% CI: −3.23 to −2.53, p < 0.001) and full weight-bearing time ( WMD = −2.81, 95% CI: −3.64 to −1.97, p < 0.001) than PLP fixation method. Meanwhile, IMN fixation resulted in lower risks of infection ( RR = 0.50, 95% CI: 0.27 to 0.91, p = 0.02) and total complications ( RR = 0.36, 95% CI: 0.22 to 0.60, p < 0.001) than PLP fixation. No significant differences were found in the incidence of nonunion ( p = 0.33), malunion ( p = 0.38), and osteofascial compartment syndrome (OCS, p = 0.62) between the two groups. Conclusions: Compared to PLP fixation, IMN fixation had several advantages in treating proximal tibial fractures, including the short time of union and full weight-bearing, as well as a low risk of infection and total complications.
Preventing Falls and Malnutrition among Older Adults in Municipal Residential Care in Sweden: A Registry Study
Authors: Gusdal Annelie K. , Johansson-Pajala Rose-Marie , Arkkukangas Marina , Ekholm Anna , Zander Viktoria 
Published: July 2021

Introduction Older adults in municipal residential care are among the most vulnerable and in need of most care. The prevalence of negative events, such as falls and malnutrition, is increased among these older adults. The need for strategies to prevent falls and malnutrition is emphasized in guidelines and systematic, individualized risk assessments are prerequisites for adequate interventions. Objectives The overall purpose of this study was to investigate the assessed risks of, and risk factors for, falling and malnutrition and the correlations between these assessed risks among older women and men in residential care. Further, the purpose was to investigate the consistency between planned and performed interventions among women and men assessed as at risk. Methods A cross-sectional registry study based on risk assessment data in the Swedish national quality registry, Senior Alert. Altogether, 5,919 older adults ≥65 in nursing homes and dementia care units in 19 municipalities in Sweden were included. Results Of the older adults, 77% were at risk of falls, and 59% were at risk of malnutrition. The most prevalent risk factors for falls were previous falls and not being cognitively oriented; and for malnutrition were having mild or severe dementia or depression. A significant positive correlation between the risk of falling and the risk of malnutrition was found. Less than half of the planned interventions for falls and malnutrition were performed. Care staff’s least common interventions to prevent falls were balance, muscular function, and strength training, which contrasts with the recommendations; interventions to prevent malnutrition were only partially adhering to recommendations. Conclusions This cross-sectional registry study points towards the importance of using an evidence-based approach, based on adherence to recommended guidelines, in the prevention of falling and malnutrition. Further, the implementation of clinical practice guidelines is needed, which requires educational training for care staff and supportive leadership.
Gene therapy for hemophilia: a review on clinical benefit, limitations, and remaining issues
Authors: Leebeek Frank W. G. , Miesbach Wolfgang 
Published: July 2021

Abstract
In the last decade, enormous progress has been made in the development of gene therapy for hemophilia A and B. After the first encouraging results of intravenously administered adeno-associated virus (AAV)-based liver-directed gene therapy in patients with severe hemophilia B were reported in 2011, many gene therapy studies have been initiated. Most of these studies, using AAV vectors with various gene constructs, showed sufficient factor VIII and IX expression in patients to significantly reduce the number of bleeds and the need for prophylaxis in most patients with severe hemophilia. This resulted in great clinical benefit for nearly all patients. In this review, we will summarize the most recent findings of reported and ongoing gene therapy trials. We will highlight the successful outcome of trials with focus on the results of recently reported phase 1 trials and preliminary results of phase 2b/3 trials for hemophilia A and B. These new reports also reveal the impact of side effects and drawbacks associated with gene therapy. We will therefore also discuss the limitations and remaining issues of the current gene therapy approaches. These issues must be resolved before gene therapy will be widely available for the hemophilia patient population.
The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma
Authors: Eluard Baptiste , Nuan-Aliman Stéphanie , Faumont Nathalie , Collares Davi , Bordereaux Didier , Montagne Aurélie , Martins Isabelle , Cagnard Nicolas , Caly Martial , Taoui Oussama , Lordello Leonardo , Lehmann-Che Jacqueline , Tesson Bruno , Martinez-Climent Jose-Angel , Copie-Bergman Christiane , Haioun Corinne , Tilly Hervé , Bonsang Benjamin , Vincent-Salomon Anne , Jais Jean-Philippe , Jardin Fabrice , Leroy Karen , Maiuri Maria Chiara , Kroemer Guido , Molina Thierry Jo , Feuillard Jean , Baud Véronique 
Published: July 2021

Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy affecting adults. The NF-κB transcription factor family is activated by 2 main pathways, the canonical and the alternative NF-κB activation pathway, with different functions. The alternative NF-κB pathway leads to activation of the transcriptionally active RelB NF-κB subunit. Alternative NF-κB activation status and its role in DLBCL pathogenesis remain undefined. Here, we reveal a frequent activation of RelB in a large cohort of DLBCL patients and cell lines, independently of their activated B-cell–like or germinal center B-cell–like subtype. RelB activity defines a new subset of patients with DLBCL and a peculiar gene expression profile and mutational pattern. Importantly, RelB activation does not correlate with the MCD genetic subtype, enriched for activated B-cell–like tumors carrying MYD88L265P and CD79B mutations that cooperatively activate canonical NF-κB, thus indicating that current genetic tools to evaluate NF-κB activity in DLBCL do not provide information on the alternative NF-κB activation. Furthermore, the newly defined RelB-positive subgroup of patients with DLBCL exhibits a dismal outcome after immunochemotherapy. Functional studies revealed that RelB confers DLBCL cell resistance to DNA damage–induced apoptosis in response to doxorubicin, a genotoxic agent used in the front-line treatment of DLBCL. We also show that RelB positivity is associated with high expression of cellular inhibitor of apoptosis protein 2 (cIAP2). Altogether, RelB activation can be used to refine the prognostic stratification of DLBCL and may contribute to subvert the therapeutic DNA damage response in a segment of patients with DLBCL.
CYB561A3 is the key lysosomal iron reductase required for Burkitt B-cell growth and survival
Authors: Wang Zhonghao , Guo Rui , Trudeau Stephen J. , Wolinsky Emma , Ast Tslil , Liang Jin Hua , Jiang Chang , Ma Yijie , Teng Mingxiang , Mootha Vamsi K. , Gewurz Benjamin E. 
Published: July 2021

Abstract
Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma, the leading childhood cancer in sub-Saharan Africa. Burkitt cells retain aspects of germinal center B-cell physiology with MYC-driven B-cell hyperproliferation; however, little is presently known about their iron metabolism. CRISPR/Cas9 analysis highlighted the little-studied ferrireductase CYB561A3 as critical for Burkitt proliferation but not for that of the closely related EBV-transformed lymphoblastoid cells or nearly all other Cancer Dependency Map cell lines. Burkitt CYB561A3 knockout induced profound iron starvation, despite ferritinophagy ad plasma membrane transferrin upregulation. Elevated concentrations of ascorbic acid, a key CYB561 family electron donor, or the labile iron source ferrous citrate rescued Burkitt CYB561A3 deficiency. CYB561A3 knockout caused catastrophic lysosomal and mitochondrial damage and impaired mitochondrial respiration. Conversely, lymphoblastoid B cells with the transforming EBV latency III program were instead dependent on the STEAP3 ferrireductase. These results highlight CYB561A3 as an attractive therapeutic Burkitt lymphoma target.
DeepHBV: a deep learning model to predict hepatitis B virus (HBV) integration sites
Authors: Wu Canbiao , Guo Xiaofang , Li Mengyuan , Shen Jingxian , Fu Xiayu , Xie Qingyu , Hou Zeliang , Zhai Manman , Qiu Xiaofan , Cui Zifeng , Xie Hongxian , Qin Pengmin , Weng Xuchu , Hu Zheng , Liang Jiuxing 
Published: July 2021

AbstractBackgroundThe hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation.ResultsAn attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites. By learning local genomic features automatically, DeepHBV was trained and tested using HBV integration site data from the dsVIS database. Initially, DeepHBV showed an AUROC of 0.6363 and an AUPR of 0.5471 for the dataset. The integration of genomic features of repeat peaks and TCGA Pan-Cancer peaks significantly improved model performance, with AUROCs of 0.8378 and 0.9430 and AUPRs of 0.7535 and 0.9310, respectively. The transcription factor binding sites (TFBS) were significantly enriched near the genomic positions that were considered. The binding sites of the AR-halfsite, Arnt, Atf1, bHLHE40, bHLHE41, BMAL1, CLOCK, c-Myc, COUP-TFII, E2A, EBF1, Erra, and Foxo3 were highlighted by DeepHBV in both the dsVIS and VISDB datasets, revealing a novel integration preference for HBV.ConclusionsDeepHBV is a useful tool for predicting HBV integration sites, revealing novel insights into HBV integration-related carcinogenesis.
Sequoia: an interactive visual analytics platform for interpretation and feature extraction from nanopore sequencing datasets
Authors: Koonchanok Ratanond , Daulatabad Swapna Vidhur , Mir Quoseena , Reda Khairi , Janga Sarath Chandra 
Published: July 2021

Abstract
Background
Direct-sequencing technologies, such as Oxford Nanopore’s, are delivering long RNA reads with great efficacy and convenience. These technologies afford an ability to detect post-transcriptional modifications at a single-molecule resolution, promising new insights into the functional roles of RNA. However, realizing this potential requires new tools to analyze and explore this type of data.

Result
Here, we present Sequoia, a visual analytics tool that allows users to interactively explore nanopore sequences. Sequoia combines a Python-based backend with a multi-view visualization interface, enabling users to import raw nanopore sequencing data in a Fast5 format, cluster sequences based on electric-current similarities, and drill-down onto signals to identify properties of interest. We demonstrate the application of Sequoia by generating and analyzing ~ 500k reads from direct RNA sequencing data of human HeLa cell line. We focus on comparing signal features from m6A and m5C RNA modifications as the first step towards building automated classifiers. We show how, through iterative visual exploration and tuning of dimensionality reduction parameters, we can separate modified RNA sequences from their unmodified counterparts. We also document new, qualitative signal signatures that characterize these modifications from otherwise normal RNA bases, which we were able to discover from the visualization.

Conclusions
Sequoia’s interactive features complement existing computational approaches in nanopore-based RNA workflows. The insights gleaned through visual analysis should help users in developing rationales, hypotheses, and insights into the dynamic nature of RNA. Sequoia is available at https://github.com/dnonatar/Sequoia.
Incidence of in-hospital cardiac arrest at general wards before and after implementation of an early warning score
Authors: Creutzburg Andreas , Isbye Dan , Rasmussen Lars S. 
Published: July 2021

Abstract
Background
In order to reduce the incidence of in-hospital cardiac arrest (IHCA) at general wards, medical emergency teams (MET) were implemented in the Capital Region of Denmark in 2012 as the efferent part of a track and trigger system. The National Early Warning Score (NEWS) system became the afferent part. This study aims at investigating the incidence of IHCA at general wards before and after the implementation of the NEWS system.

Material and methods
We included patients at least 18 years old with IHCA at general wards in our hospital in the periods of 2006 to 2011 (pre-EWS group) and 2013 to 2018 (post-EWS group). Data was obtained from a local database and the National In-Hospital Cardiac Arrest Registry (DANARREST). We calculated incidence rate ratios (IRR) for IHCA at general wards with 95% confidence interval (95% CI). Odds ratios (OR) for return of spontaneous circulation (ROSC) and 30-day survival were also calculated with 95% CI.

Results
A total of 444 IHCA occurred before the implementation of NEWS at general wards while 494 IHCA happened afterwards. The incidence rate of IHCA at general wards was 1.13 IHCA per 1000 admissions in the pre-EWS group (2006–2011) and 1.11 IHCA per 1000 admissions in the post-EWS group (2013–2018). The IRR between the two groups was 0.98 (95% CI [0.86;1.11], p = 0.71). The implementation did not affect the chance of ROSC with a crude OR of 1.14 (95% CI [0.88;1.47], p = 0.32) nor did it change the 30-day survival with a crude OR 1.30 (95% CI [0.96;1.75], p = 0.09).

Conclusion
Implementation of the EWS system at our hospital did not decrease the incidence rate of in-hospital cardiac arrest at general wards.
Consequences of ignoring clustering in linear regression
Authors: Ntani Georgia , Inskip Hazel , Osmond Clive , Coggon David 
Published: July 2021

Abstract
Background
Clustering of observations is a common phenomenon in epidemiological and clinical research. Previous studies have highlighted the importance of using multilevel analysis to account for such clustering, but in practice, methods ignoring clustering are often employed. We used simulated data to explore the circumstances in which failure to account for clustering in linear regression could lead to importantly erroneous conclusions.

Methods
We simulated data following the random-intercept model specification under different scenarios of clustering of a continuous outcome and a single continuous or binary explanatory variable. We fitted random-intercept (RI) and ordinary least squares (OLS) models and compared effect estimates with the “true” value that had been used in simulation. We also assessed the relative precision of effect estimates, and explored the extent to which coverage by 95% confidence intervals and Type I error rates were appropriate.

Results
We found that effect estimates from both types of regression model were on average unbiased. However, deviations from the “true” value were greater when the outcome variable was more clustered. For a continuous explanatory variable, they tended also to be greater for the OLS than the RI model, and when the explanatory variable was less clustered. The precision of effect estimates from the OLS model was overestimated when the explanatory variable varied more between than within clusters, and was somewhat underestimated when the explanatory variable was less clustered. The cluster-unadjusted model gave poor coverage rates by 95% confidence intervals and high Type I error rates when the explanatory variable was continuous. With a binary explanatory variable, coverage rates by 95% confidence intervals and Type I error rates deviated from nominal values when the outcome variable was more clustered, but the direction of the deviation varied according to the overall prevalence of the explanatory variable, and the extent to which it was clustered.

Conclusions
In this study we identified circumstances in which application of an OLS regression model to clustered data is more likely to mislead statistical inference. The potential for error is greatest when the explanatory variable is continuous, and the outcome variable more clustered (intraclass correlation coefficient is ≥ 0.01).