bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient multiplexed gene regulation inSaccharomyces cerevisiaeusing dCas12a
Authors: Ciurkot Klaudia , Gorochowski Thomas E , Roubos Johannes A , Verwaal René 
Published: June 2021

AbstractCRISPR Cas12a is an RNA-programmable endonuclease particularly suitable for gene regulation. This is due to its preference for T-rich PAMs that allows it to more easily target AT-rich promoter sequences, and built-in RNase activity which can process a single CRISPR RNA array encoding multiple spacers into individual guide RNAs (gRNAs), thereby simplifying multiplexed gene regulation. Here, we develop a flexible dCas12a-based CRISPRi system for Saccharomyces cerevisiae and systematically evaluate its design features. This includes the role of the NLS position, use of repression domains, and the position of the gRNA target. Our optimal system is comprised of dCas12a E925A with a single C-terminal NLS and a Mxi1 or a MIG1 repression domain, which enables up to 97% downregulation of a reporter gene. We also extend this system to allow for inducible regulation via an RNAP II-controlled promoter, demonstrate position-dependent effects in crRNA arrays, and use multiplexed regulation to stringently control a heterologous β-carotene pathway. Together these findings offer valuable insights into the design constraints of dCas12a-based CRISPRi and enable new avenues for flexible and efficient gene regulation in S. cerevisiae.
High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study
Authors: Flower Barnaby , McCabe Leanne , Le Ngoc Chau , Le Manh Hung , Le Thanh Phuong , Dang Trong Thuan , Vo Thi Thu , Vu Thi Kim Hang , Nguyen Tat Thanh , Phan Thi Hong Dao , Nguyen Thi Chau An , Dinh Thi Tan , Tran Thi Tuyet Nga , Tarning Joel , Kingsley Cherry , Kestelyn Evelyne , Pett Sarah L , Thwaites Guy , Nguyen Van Vinh Chau , Smith David , Barnes Eleanor , Ansari M Azim , Turner Hugo , Rahman Motiur , Walker Ann Sarah , Day Jeremy , Cooke Graham S 
Published: June 2021

Abstract

Background
Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis.

Methods
In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load &lt;500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR).

Results
Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load &lt;500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline.

Conclusions
Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is &lt;5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
Neck circumference and the burden of metabolic syndrome disease: a population-based sample
Authors: Zanuncio V V , Sediyama C M N O , Dias M M , Nascimento G M , Pessoa M C , Pereira P F , Silva M R I , Segheto K J , Longo G Z 
Published: June 2021

Abstract

Background
This study aims to verify the association between neck circumference (NC) and metabolic syndrome and establish NC cut-off points to predict metabolic syndrome.

Methods
Weight, height, NC, waist circumference, body mass index, fasting plasma glucose, HDL cholesterol, triglycerides and blood pressure were measured in a cross-sectional and population-based study with 966 adults. The association between NC and the burden of metabolic syndrome disease was evaluated by multinomial logistic regression. Receiver operating characteristic curves were used to acquire gender-specific cut-off values and predict metabolic syndrome. The NC is a simple anthropometric measurement, has low evaluation costs, can estimate the subcutaneous fat in the upper body and is related to cardiometabolic risks.

Results
NC is an independent predictor of metabolic syndrome burden with high association to women. The syndrome components stratification indicated that the NC of individuals with one component was lower than those with three or more (P = 0.001). Metabolic syndrome prediction cut-off point was a NC of 39.5 cm for men and 33.3 cm for women.

Conclusions
Increased NC was associated with higher metabolic syndrome risks. This anthropometric parameter can be used as an additional marker for screening cardiovascular risk diseases.
Optimal sleep and work schedules to maximize alertness
Authors: Vital-Lopez Francisco G , Doty Tracy J , Reifman Jaques 
Published: June 2021

Abstract

Study Objectives
Working outside the conventional “9-to-5” shift may lead to reduced sleep and alertness impairment. Here, we developed an optimization algorithm to identify sleep and work schedules that minimize alertness impairment during work hours, while reducing impairment during non-work hours.

Methods
The optimization algorithm searches among a large number of possible sleep and work schedules and estimates their effectiveness in mitigating alertness impairment using the Unified Model of Performance (UMP). To this end, the UMP, and its extensions to estimate sleep latency and sleep duration, predicts the time course of alertness of each potential schedule and their physiological feasibility. We assessed the algorithm by simulating four experimental studies, where we compared alertness levels during work periods for sleep schedules proposed by the algorithm against those used in the studies. In addition, in one of the studies we assessed the algorithm’s ability to simultaneously optimize sleep and work schedules.

Results
Using the same amount of sleep as in the studies but distributing it optimally, the sleep schedules proposed by the optimization algorithm reduced alertness impairment during work periods by an average of 29%. Similarly, simultaneously optimized sleep and work schedules, for a recovery period following a chronic sleep restriction challenge, accelerated the return to baseline levels by two days when compared to the conventional 9-to-5 work schedule.

Conclusions
Our work provides the first quantitative tool to optimize sleep and work schedules and extends the capabilities of existing fatigue-management tools.
Electoral Rules, Nomination Strategies, and Women’s Representation in Japan and Taiwan
Authors: Lin Chao-Chi , YANG Wan-Ying 
Published: June 2021

AbstractJapan and Taiwan conducted similar electoral reforms in 1994 and 2005. Following the transition from the single nontransferable vote (SNTV) to the mixed-member majoritarian (MMM), at the district level, both countries’ numbers of female representatives have increased, contrary to expectations. What, then, explains the increase in Japan’s and Taiwan’s women’s representation at the district level? We argue that electoral systems can only partly explain the variation in female representation and that the critical factor explaining women’s representation is not the women’s electability, but the earlier stage of nomination. This article examines continuity and change in the candidate selection methods of major parties in Japan and Taiwan and identifies factors that may affect the likelihood of women becoming candidates. Although major parties have adopted different nomination strategies following the reforms, the increase in female representatives has been associated with the centralized process, and whether a woman is an incumbent or not is key to her nomination. Moreover, path dependence matters, and given that Taiwan had more female incumbent representatives than Japan under the SNTV, this might explain the differences in the starting point for female representation between Taiwan and Japan when both switched to the MMM and there was a persistent gap between the two countries.
RV144 vaccine imprinting constrained HIV-1 evolution following breakthrough infection
Authors: Lewitus Eric , Sanders-Buell Eric , Bose Meera , O’Sullivan Anne Marie , Poltavee Kultida , Li Yifan , Bai Hongjun , Mdluli Thembi , Donofrio Gina , Slike Bonnie , Zhao Hong , Wong Kim , Chen Lennie , Miller Shana , Lee Jenica , Ahani Bahar , Lepore Steven , Muhammad Sevan , Grande Rebecca , Tran Ursula , Dussupt Vincent , Mendez-Rivera Letzibeth , Nitayaphan Sorachai , Kaewkungwal Jaranit , Pitisuttithum Punnee , Rerks-Ngarm Supachai , O’Connell Robert J , Janes Holly , Gilbert Peter B , Gramzinski Robert , Vasan Sandhya , Robb Merlin L , Michael Nelson L , Krebs Shelly J , Herbeck Joshua T , Edlefsen Paul T , Mullins James I , Kim Jerome H , Tovanabutra Sodsai , Rolland Morgane 
Published: June 2021

Abstract
The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1’s high evolvability hints that HIV-1 could adapt to a future vaccine. Here, we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signature sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll-out.
Human genomics of the humoral immune response against polyomaviruses
Authors: Hodel F , Chong A Y , Scepanovic P , Xu Z M , Naret O , Thorball C W , Rüeger S , Marques-Vidal P , Vollenweider P , Begemann M , Ehrenreich H , Brenner N , Bender N , Waterboer T , Mentzer A J , Hill A V S , Hammer C , Fellay J 
Published: June 2021

Abstract
Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.
Creative Ways to Enhance and Assess Critical Thinking in Nursing Students
Authors: Parker Kimberly C. 
Published: June 2021

Abstract
Nursing students should be challenged to implement critical thinking decisions regarding conclusions they implement for patient care. This article reinforces common techniques and introduces new practices to teach critical thinking. Many ways are currently recognized utilizing an assortment of techniques. The concepts from an escape room are a great way to deliver opportunities for students to practice this skill and can be provided economically and easily. Being creative in managing these concepts will offer an exciting chance to introduce critical thinking for your students.
Characterizing Health-Related Quality of Life by Ambulatory Status in Patients with Spinal Metastases
Authors: Schoenfeld Andrew J. , Yeung Caleb M. , Tobert Daniel G. , Nguyen Lananh , Passias Peter G. , Shin John H. , Kang James D. , Ferrone Marco L. 
Published: June 2021

Study Design.
Retrospective review of prospective longitudinal data.

Objective.
To determine health-related quality of life (HRQL) utilities associated with specific ambulatory states in patients with spinal metastases: independent, ambulatory with assistance, and nonambulatory.

Summary of Background Data.
It is assumed that HRQL is aligned with ambulatory ability in patients with spinal metastases. Few studies have effectively considered these parameters while also accounting for clinical confounders.

Methods.
We used prospective longitudinal data from patients treated at one of three tertiary medical centers (2017–2019). HRQL was characterized using the Euroquol-5-dimension (EQ5D) inventory. We performed standardized estimations of HRQL stratified by ambulatory state using generalized linear modeling that accounted for patient age at presentation, biologic sex, follow-up duration, operative or nonoperative management, and repeated measures within the same participant.

Results.
We evaluated 675 completed EQ5D assessments, with 430 for independent ambulators, 205 for ambulators with assistance, and 40 for nonambulators. The average age of the cohort was 61.5. The most common primary cancer was lung (20%), followed by breast (18%). Forty-one percent of assessments were performed for participants treated surgically. Mortality occurred in 51% of the cohort. The standardized EQ5D utility for patients with spinal metastases and independent ambulatory function was 0.76 (95% confidence interval [CI] 0.74, 0.78). Among those ambulatory with assistance, the standardized EQ5D utility was 0.59 (95% CI 0.57, 0.61). For nonambulators, the standardized EQ5D utility was 0.14 (95% CI 0.09, 0.19).

Conclusion.
Patients with spinal metastases and independent ambulatory function have an HRQL similar to patients with primary cancers and no spinal involvement. Loss of ambulatory ability leads to a 22% decrease in HRQL for ambulation with assistance and an 82% reduction among nonambulators. Given prior studies demonstrate superior maintenance of ambulatory function with surgery for spinal metastases, our results support surgical consideration to the extent that it is clinically warranted.

Level of Evidence: 3
Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial
Authors: Kadry Zakiyah , Stine Jonathan G. , Dohi Takehiko , Jain Ashokkumar , Robyak Kimberly L. , Kwon Osun , Hamilton Christopher J. , Janicki Piotr , Riley Thomas R. , Butt Fauzia , Krok Karen , Schreibman Ian R. , Bezinover Dmitri , Ghahramani Nasrollah , Campos Stalin , Hollenbeak Christopher S. 
Published: June 2021

Background.
Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months.

Methods.
This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson’s chi-square test for binary outcomes. Effect size was measured using Cohen’s d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test.

Results.
Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months.

Conclusions.
EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.
Robustness and bias of European excess death estimates in 2020 under varying model specifications
Authors: Schöley Jonas 
Published: June 2021

AbstractVarious procedures are in use to calculate excess deaths during the ongoing COVID-19 pandemic. Using weekly death counts from 20 European countries, we evaluate the robustness of excess death estimates to the choice of model for expected deaths and perform a cross-validation analysis to assess the error and bias in each model’s predicted death counts. We find that the different models produce very similar patterns of weekly excess deaths but disagree substantially on the level of excess. While the exact country ranking along percent excess death in 2020 is sensitive to the choice of model the top and bottom ranks are robustly identified. On the country level, the 5-year average death rate model tends to produce the lowest excess death estimates, whereas high excess deaths are produced by the popular 5-year average death count and Euromomo-style Serfling models. Cross-validation revealed these estimates to be biased under a causal interpretation of “expected deaths had COVID-19 not happened.”
The mental health impact of COVID-19 racial and ethnic discrimination against Asian American and Pacific Islanders
Authors: Zhou Sasha , Banawa Rachel , Oh Hans 
Published: June 2021

ABSTRACTHate crimes against Asian American/ Pacific Islanders (AAPIs) have surged in the United States during the COVID-19 pandemic to alarming new levels. We analyzed data from the Healthy Minds Study, and found that COVID-19 related racial/ethnic discrimination was associated with greater odds of having depression, anxiety, non-suicidal self-injury, binge drinking, and suicidal ideation among AAPI university students (N=1697). Findings suggest that the COVID-19 pandemic precipitated discrimination, which has been linked to mental health problems, calling for more preventive interventions to address the AAPI population, especially given their low rates of formal treatment utilization.
Post-COVID-19 Perceived Stigma-Discrimination Scale: Psychometric Development and Evaluation
Authors: Cassiani-Miranda Carlos Arturo , Pedrozo-Pupo John Carlos , Campo-Arias Adalberto 
Published: June 2021

AbstractThe COVID-19 survivors face social stigmatization, even with negative tests. Valid and reliable instruments are required to quantify the stigma-discrimination complex associated with COVID-19 (COVID-19-CED). The study aimed to adapt and evaluate a scale to measure COVID-19-CED in COVID-19 survivors. A validation study was done with 330 COVID-19 survivors between 18 and 89 years. The COVID-19 Perceived Discrimination Scale (C-19-PDS) was used, which was adapted from the Tuberculosis Perceived Discrimination Scale. An exploratory factor analysis (EFA), confirmatory factor analysis (CFA), internal consistency, and differential item functioning (DIF) were performed using the classical theory of tests. EFA showed a one-dimensional solution for the items of C-19-PDS; however, CFA showed poor goodness-of-fit indicators. The 5-item version of the C-19-PDS showed better goodness-of-fit indicators, high internal consistency, and non-gender DIF. In conclusion, the 5-item version of the C-19-PDS is one-dimensional, with high internal consistency, and without gender DIF. This instrument is recommended to evaluate COVID-19-CED in the Colombian population.
Antipsychotic Drugs and the Risk of Breast Cancer
Authors: Rahman Tahir , Sahrmann John M. , Olsen Margaret A. , Nickel Katelin B. , Miller J. Phillip , Ma Cynthia , Grucza Richard A. 
Published: June 2021

AbstractObjectiveAntipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium.MethodsThe IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories.ResultsA total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant.ConclusionIn the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.
g-CXR-Net: A Graphic Application for the Rapid Recognition of SARS-CoV-2 from Chest X-Rays
Authors: Gatti Domenico L. 
Published: June 2021

Abstractg-CXR-Net is a graphic application for the rapid recognition of SARS-CoV-2 from Antero/Posterior chest X-rays. It employs the Artificial Intelligence engine of CXR-Net (arXiv:2103.00087) to generate masks of the lungs overlapping the heart and large vasa, probabilities for Covid vs. non-Covid assignment, and high resolution heat maps that identify the SARS associated lung regions.