bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma
Authors: Lei Hoa-Jan , Wang Sheng-Yu , Chau Ivy Yenwen , Li Anna Fen-Yau , Chau Yat-Pang , Hsia Cheng-Yuan , Chou Shu-Cheng , Kao Yi-Chu , Chau Gar-Yang 
Published: April 2021

Background:
Hepatoma upregulated protein (HURP) and Ki-67 have been identified as cancer-related genes involved in cell growth and proliferation. Previous experimental studies have suggested an essential role for HURP expression in liver carcinogenesis. However, data regarding HURP expression in hepatocellular carcinoma (HCC) and its correlation with patient outcomes are limited. In this study, we examined the clinicopathologic features associated with HURP expression in HCC, and compared them to the results of the Ki-67 study.

Methods:
Eighty-seven resected HCC at tumor, node, metastasis (TNM) stages I (n = 28), II (n = 29), and III (n = 30) were evaluated. HURP and Ki-67 expression were assessed by immunohistochemistry. Multivariate analysis was used to examine the prognostic significance of HURP and Ki-67 expression.

Results:
HURP expression in HCC tissue was observed in 59% of patients and associated with female sex, low white blood cell count, and low platelet count. Ki-67 expression was observed in 67% of patients and associated with younger age, higher serum α-fetoprotein (AFP) levels, and frequent microvascular invasion. Univariate analysis showed that factors related to overall survival were: age >55 years, AFP >20 ng/mL, indocyanine green retention rate at 15 minutes (ICG-15) >15%, tumor size >5 cm, multiple tumors, macrovascular invasion, microvascular invasion, Ki-67 expression, and serum vascular endothelial growth factor >170 pg/mL. HURP expression was not associated with postresection survival. Multivariate analysis indicated that macrovascular invasion, multiple tumors, ICG-15 >15%, and Ki-67 expression were independent factors for overall survival. Multiple tumors and Ki-67 expression were independent factors related to recurrence-free survival.

Conclusion:
In our study, HURP expression in HCC tissue was not associated with post-resection survival. Ki-67 expression was an independent prognostic factor for survival. Our results suggest that the effect of HURP activity on growth, invasion, and postresection outcome of HCC in actual patients is less than previously demonstrated in experimental studies.
Development and Pilot Test of an Online Training to Engage Managers to Support Workplace Wellness
Authors: Hammerback Kristen , Kava Christine M. , Passey Deborah G. , Hahn Justin , Huff Aaron , Kohn Marlana J. , Harris Jeffrey R. , Hannon Peggy A. 
Published: April 2021

Objective:
To contribute to a broader understanding of effective implementation strategies to help managers engage employees in workplace wellness.

Methods:
We beta-tested an online training at four Washington state agencies (two test, two control). We administered a post-training evaluation, re-administered an online manager survey and conducted additional interviews with wellness leads.

Results:
Training participation rate was high. The two test agencies experienced a significant increase in the percentage of managers who: agreed that they received training on employee wellness; agreed their agency's culture supports employee wellness; and encouraged their employees to participate in wellness activities. Approximately 80% of managers who received the training agreed they could apply information learned to support employee wellness.

Conclusions:
If proven effective, the training could be administered at a low cost and disseminated to improve employee health.
Evidence-Based Clinical Practice Guideline: Reconstruction after Skin Cancer Resection
Authors: Chen Andrew , Albertini John G. , Bordeaux Jeremy S. , Chen Michael W. , Cook Jonathan L. , Davidson Caryn , Donnelly Katelyn C. , Galaria Irfan I. , Hannan Catherine M. , Kantor Jonathan , Kapp Daniel L. , Lawrence Naomi , Lober Clifford W. , Loeding Lauren D. , Miller Alexander , Ness Daniel T. , Neves Rogerio I. , Revenaugh Peter C. , Setabutr Peter , Tholpady Sunil S. , Tollefson Travis T. , Van Beek Marta J. , Weiss Paul R. , Alam Murad 
Published: April 2021

Summary:
A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.
Functional and Radiographic Disease Progression in Nonoperatively Managed Kienböck Disease
Authors: DeGeorge Brent R. , Chawla Sagar S. , Lewallen Laura , Kakar Sanjeev 
Published: April 2021

Background:
The purpose of this study was to describe the natural history of Kienböck disease among patients who elected to proceed with nonoperative treatment.

Methods:
The authors performed a retrospective study of all patients treated nonoperatively for Kienböck disease within their institution from January 1, 1999, to December 31, 2014. Inclusion criteria included follow-up greater than 1 year, serial posteroanterior and lateral wrist radiographs, and clinical examination. Posteroanterior/lateral radiographs were independently reviewed at initial presentation and at final follow-up, including Lichtman stage, carpal index, Stahl index, ulnar variance, and intercarpal angles.

Results:
Twenty-five patients with 25 wrists were included (mean age, 50.2 years), with an average length of clinical follow-up of 3.9 years and a mean length of radiographic follow-up of 5.2 years. There was no significant difference in range of motion; however, patient-reported pain was significantly decreased, and modified Mayo wrist scores and grip strength were increased. Lichtman stage, scapholunate angle, and radioscaphoid angle were increased; and carpal index, posteroanterior lunate ratio, and Stahl index were decreased across the study period. The mean progression in Lichtman stage was 0.5 stage/year with a range of 0 to 1.6 stages/year throughout the study period. There was no significant difference in Lichtman stage progression based on stage at presentation. A history of smoking was associated with increased radiographic disease progression.

Conclusion:
The present study demonstrates that among patients with Kienböck disease managed nonoperatively, the majority of patients significantly improve over time with respect to pain, grip strength, and Mayo wrist score, despite radiographic progression of disease.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, IV.
Reaching Those Most at Risk for HIV Acquisition: Evaluating Racial/Ethnic Disparities in the Preexposure Prophylaxis Care Continuum in Baltimore City, Maryland
Authors: Schumacher Christina M. , Tao Xueting , Chandran Aruna , Fields Errol , Price Ashley , Greenbaum Adena , Jennings Jacky M. ,   the IMPACT Partner Collaborative
Published: April 2021

Background:
Reducing HIV incidence requires addressing persistent racial/ethnic disparities in HIV burden. Our goal was to evaluate preexposure prophylaxis (PrEP) delivery, overall and relative to community need, among 7 clinical sites participating in a health department–led demonstration project to increase PrEP in Baltimore city, MD.

Methods:
PrEP care continuum stages (screened, indicated, referred, linked, evaluated, prescribed) were examined among HIV-negative individuals receiving services at participating sites between September 30, 2015 and September 29, 2019. Community need was defined using information on new HIV diagnoses (2016–2018). Differences in care continuum progression by demographics/priority population and comparison of demographic compositions between care continuum stages and new HIV diagnoses were examined using modified Poisson regression and χ2 tests, respectively.

Results:
Among 25,886 PrEP-screened individuals, the majority were non-Hispanic (NH) black (81.1%, n = 20,998), cisgender male (61.1%, n = 15,825), and heterosexual (86.7%, n = 22,452). Overall, 31.1% (n = 8063) were PrEP-indicated; among whom, 56.8% (n = 4578), 15.6% (n = 1250), 10.8% (n = 868), and 9.0% (n = 722) were PrEP-referred, linked, evaluated, and prescribed, respectively. Among 2870 men who have sex with men (MSM), 18.7% (n = 538) were PrEP-prescribed. Across all groups, the highest attrition was between PrEP-referred and PrEP-linked. NH-black race (vs. NH-white) was independently associated with lower likelihood of PrEP prescription (aPR, 0.89; 95% confidence interval, 0.81 to 0.98 controlling for age/gender). Relative to the demographic composition of new HIV diagnoses, fewer NH-blacks (80.2% vs. 54.3%) and more NH-whites (10.7% vs. 30.3%) and MSM were PrEP prescribed (55.2% vs. 74.5%).

Conclusions:
This project showed promise delivering PrEP referrals and prescriptions overall and to MSM. Substantial improvement is needed to improve linkage overall and to decrease disparities in PrEP prescriptions among NH-blacks. Future work should focus on addressing service gaps that hinder PrEP utilization.
Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum
Authors: Boxer Emma E , Seng Charlotte , Lukacsovich David , Kim JungMin , Schwartz Samantha , Kennedy Matthew J , Földy Csaba , Aoto Jason 
Published: April 2021

AbstractVentral subiculum (vSUB) is integral to the regulation of stress and reward, however the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular spiking (RS) and burst spiking (BS) principal neurons. Surprisingly, we found that intrinsic connectivity and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that vSUB PVs make preferential contact with RS neurons in males, but BS neurons in females. Furthermore, we determined that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 maintains synapse density at PV-RS synapses in males, but suppresses presynaptic release at the same synapses in females.HighlightsOverall inhibitory strength in ventral subiculum is cell-type specificPV circuits in ventral subiculum are organized sex-specificallyNrxn3 function in PV interneurons depends on postsynaptic cell identityNrxn3 has distinct functions at PV-RS synapses in females compared to malesAbstract FigureGraphical Abstract
Interleukin-15 Receptor α Chain Knockout NOD-SCID mice have reduced numbers of NK cells, develop thymic lymphomas and fail to engraft human hematopoietic cells
Authors: Vecchione Andrea , Nauman Grace , Marharlooei Mohsen Khosravi , Danzl Nichole , Li Hao-Wei , Chavez Estefania , Low Benjamin E. , Wiles Michael V. , Serreze David , Ding Lei , Sykes Megan 
Published: April 2021

AbstractNOD-SCID IL2rγcnull(NSG) mice are widely used to model human immune cell development because they are more permissive for human hematopoietic cell engraftment and reconstitution than NOD-SCID mice. While increased human reconstitution in the blood of NSG mice has been attributed to the absence of mouse NK cells, deletion of the common gamma chain (γc) limits development of lymphoid tissue inducer cells and precludes development of normal secondary lymphoid structures. The disorganized lymphoid tissue leads to compromised human T cell-B cell interactions and results in variable human immune cell function in human immune system (HIS) NSG compared to NOD-SCID mice. We attempted to remove mouse NK cells from NOD-SCID mice while retaining other γc-dependent cytokine responses by targeted disruption of the mouse genomicIL15RAlocus with CRISPR/Cas9. IL15Rα is required for the development, function and survival of NK cells. NOD-SCID IL15Rα-/-mice showed reductions in NK cells and NK cell function. However, NOD-SCID IL15Rα-/-mice demonstrated accelerated thymic lymphomagenesis and showed earlier mortality compared to NOD-SCID mice. This result suggests that mouse NK cells are important to delay lymphoma development in NOD-SCID mice. We transplanted thymectomized NOD-SCID ILl5Rα-/-mice with human fetal liver CD34+cells and thymus to determine if these mice supported engraftment and development of a transplanted HIS. Surprisingly, we found that peripheral human engraftment was inferior (mean 0.05% of lymphocytes) to that in both NOD-SCID (mean, 10.5% of lymphocytes) and NSG (mean, 54% of lymphocytes) mice. These results indicate that NOD-SCID IL15Rα-/-mice are not permissive for human CD34+cell engraftment.
Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding
Authors: Alenquer Marta , Ferreira Filipe , Lousa Diana , Valério Mariana , Medina-Lopes Mónica , Bergman Marie-Louise , Gonçalves Juliana , Demengeot Jocelyne , Leite Ricardo B. , Lilue Jingtao , Ning Zemin , Penha-Gonçalves Carlos , Soares Helena , Soares Cláudio M. , Amorim Maria João 
Published: April 2021

AbstractUnderstanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, with the effect of mutation synergy still incompletely understood. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations, and confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations.In silicoanalysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and N501Y. Our analysis of synergic mutations provides a landscape for hotspots for immune evasion and for targets for therapies, vaccines and diagnostics.One-Sentence SummaryAmino acids in SARS-CoV-2 spike protein implicated in immune evasion are biased for binding to neutralizing antibodies but dispensable for binding the host receptor angiotensin-converting enzyme
A novel magnetic bead-based extraction method for the isolation of antimicrobial resistance genes with a case study in river water in Malawi
Authors: Byrne Rachel L. , Cocker Derek , Alyayyoussi Ghaith , Mphasa M. , Charles Mary , Mandula Tamandani , Williams Christopher T. , Rigby Jonathan , Hearn Jack , Feasey Nicholas , Adams Emily R. , Edwards Thomas 
Published: April 2021

ABSTRACTBackgroundThe environmental is increasingly recognised as an important reservoir of antimicrobial resistance (AMR) genes. Polymerase chain reaction (PCR) and whole genome sequencing (WGS) have great potential in the surveillance of AMR genes. However, molecular methods are dependent upon the isolation of high-quality DNA yields. Currently, there is no consensus for the optimum DNA extraction strategies from complex environmental matrices for downstream molecular applications.MethodsWe present a novel magnetic bead-based method for the isolation of antimicrobial resistance genes (ARGs) from river water in Malawi, named MagnaExtract. We present this with analytic limit of detection (LOD) as well as a case study in Southern Malawi. Here we compare the DNA yield and subsequent PCR output from MagnaExtract with commercially available QIAGEN kits and the crude boil and spin method, utilising a high-resolution melt analysis (HRM) PCR panel designed for the detection of third generation cephalosporin and carbapenem resistant genes.ResultsOf the 98 water samples evaluated we found the MagnaExtract method to be comparable, and in some instance’s superior to commercially available kits for the isolation of ARGs from river water samples. In addition, we found overnight incubation to promote the recovery of extended spectrum beta-lactamase (ESBL) genes and simultaneous reduction in the detection of carbapenemase genes.ConclusionThe MagnaExtract approach offers a simple, affordable, high yielding extraction method that could be used for the detection of ARGs isolated from river water samples in environmental surveillance campaigns in East Africa.
FUS Oncofusion Protein Condensates Recruit mSWI/SNF Chromatin Remodelers via Heterotypic Interactions Between Prion-like Domains
Authors: Davis Richoo B. , Kaur Taranpreet , Moosa Mahdi Muhammad , Banerjee Priya R. 
Published: April 2021

AbstractFusion transcription factors generated by genomic translocations are common drivers of several types of cancers including sarcomas and leukemias. Oncofusions of the FET (FUS, EWSR1, and TAF15) family of proteins result from fusion of the prion-like domain (PLD) of FET proteins to the DNA-binding domain (DBD) of certain transcription regulators and are implicated in aberrant transcriptional programs through interactions with chromatin remodelers. Here, we show that FUS-DDIT3, a FET oncofusion protein, undergoes PLD-mediated phase separation into liquid-like condensates. Nuclear FUS-DDIT3 condensates can recruit essential components of the global transcriptional machinery such as the chromatin remodeler SWI/SNF. The recruitment of mammalian SWI/SNF is driven by heterotypic PLD-PLD interactions between FUS-DDIT3 and core subunits of SWI/SNF, such as the catalytic component BRG1. Further experiments with single-molecule correlative force-fluorescence microscopy support a model wherein the fusion protein forms condensates on DNA surface and enrich BRG1 to activate transcription by ectopic chromatin remodeling. Similar PLD-driven co-condensation of mSWI/SNF with transcription factors can be employed by other oncogenic fusion proteins with a genericPLD-DBD domainarchitecture for global transcriptional reprogramming.
Hydrosphere occupancy modeling (ψ) and Akaike (AIC) habitat model selection of urban amphibian in West Java landscape
Authors: Basukriadi Adi , Nurdin Erwin , Wibowo Andri 
Published: April 2021

AbstractAmphibians are animal that requires combinations of hydrosphere (riparian vegetation, water body) and vegetation (trees) microhabitats. In urban settings, those microhabitats are scarce and disappearing. One of areas that still have sufficient microhabitats to support amphibian populations is located in an 88.9 Ha urban forests of Universitas Indonesia Campus in West Java. Here, this paper aims to assess and model the several amphibian species occupancy (Ψ) with vegetation covers, riparian vegetation, and water bodies based on Akaike habitat selection (AIC) indices. The studied amphibian species includeBufo melanosticus, Hylarana nicobariensis, Fejervarya limnocharis, andPolypedates leucomystax. For modeling, 7 microhabitat models were developed and tested for amphibian species occupancy with covariates including vegetation cover, riparian vegetation, and water body microhabitats. The Principle Component Analysis (PCA) shows that the occupancies of amphibian were influenced mostly by the presences of water bodies followed by riparian vegetation, and vegetation covers. According to the values of Ψ and AIC,Polypedates leucomystaxandFejervarya limnochariswere species that have high occupancy in riparian vegetation microhabitats with Ψ values of −14.18 and −12.59. Likewise,Hylarana nicobariensishas an equal occupancy in vegetation, riparian vegetation, and water body microhabitats. WhileBufo melanosticusshows high occupancy in vegetated microhabitats (Ψ = −14.18) rather than in riparian vegetation and water bodies (Ψ = −8.79). The combinations of riparian vegetation and water bodies show higher occupancy (Ψ = −8.00) rather than Ψ(vegetation cover+water body = −5.64) and Ψ(vegetation cover+ riparian vegetation = −4.36) combinations.
Plastid phylogenomics of the Gynoxoid group (Senecioneae, Asteraceae) highlights the importance of motif-based sequence alignment amid low genetic distances
Authors: Escobari Belen , Borsch Thomas , Quedensley Taylor S. , Gruenstaeudl Michael 
Published: April 2021

ABSTRACTPREMISEThe genusGynoxysand relatives form a species-rich lineage of Andean shrubs and trees with low genetic distances within the sunflower subtribe Tussilaginineae. Previous molecular phylogenetic investigations of the Tussilaginineae have included few, if any, representatives of this Gynoxoid group or reconstructed ambiguous patterns of relationships for it.METHODSWe sequenced complete plastid genomes of 21 species of the Gynoxoid group and related Tussilaginineae and conducted detailed comparisons of the phylogenetic relationships supported by the gene, intron, and intergenic spacer partitions of these genomes. We also evaluated the impact of manual, motif-based adjustments of automatic DNA sequence alignments on phylogenetic tree inference.RESULTSOur results indicate that the inclusion of all plastid genome partitions is needed to infer fully resolved phylogenetic trees of the Gynoxoid group. Whole plastome-based tree inference suggests that the generaGynoxysandNordenstamiaare polyphyletic and form the core clade of the Gynoxoid group. This clade is sister to a clade ofAequatoriumandParagynoxysand also includes some but not all representatives ofParacalia.CONCLUSIONSThe concatenation and combined analysis of all plastid genome partitions and the construction of manually curated, motif-based DNA sequence alignments are found to be instrumental in the recovery of strongly supported relationships of the Gynoxoid group. We demonstrate that the correct assessment of homology in genome-level plastid sequence datasets is crucial for subsequent phylogeny reconstruction and that the manual post-processing of multiple sequence alignments improves the reliability of such reconstructions amid low genetic distances between taxa.