bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Walking on Fatigue in Cancer Patients
Authors: Wang Pengcheng , Wang Di , Meng Aifeng , Zhi Xiaoxu , Zhu Ping , Lu Lijing , Tang Lin , Pu Yalou , Li Xiaoli 
Published: December 2020

Background
Walking is a simple form of exercise that is easily accepted by patients. Exercise is one of the main ways to control cancer-related fatigue (CRF). However, there are conflicting data on the association between walking and severity of CRF.

Objective
The aim of this study was to assess the overall effect of walking on CRF among adult cancer patients.

Methods
Databases including PubMed, CINAHL, EMBASE, and Cochrane Library were systematically reviewed to identify suitable randomized controlled trials from inception to February 29, 2020. Two reviewers independently evaluated the risk of bias and extracted correlated data with Cochrane Handbook of Systematic Reviews on Interventions. The data analysis was performed by Review Manager 5.3.

Results
A total of 12 studies with 1064 patients were identified. Integrated result analysis of walking yielded a statistically significant effect on CRF (standard mean difference [SMD], −0.66; 95% confidence interval [CI], −1.06 to −0.26). Subgroup analysis demonstrated that intervention time longer than 6 weeks (SMD, −0.89; 95% CI, −1.22 to −0.57) had a better effect on fatigue compared with that of less than 6 weeks (SMD, 0.03; 95% CI, −0.39 to 0.45). The study showed walking was statistically more effective than the control intervention in patients undergoing cancer treatment (SMD, −0.79; 95% CI, −1.16 to −0.42). Descriptive analysis also showed that walking was effective for cancer patients who completed treatment.

Conclusions
Walking is effective for CRF during and after cancer therapy.

Implications for Practice
The results provide evidence for a general exercise form to relieve fatigue in cancer patients and facilitate support for future clinical trials and work.
Cervical Cerclage: A Review and Rethinking of Current Practice
Authors: Senarath Sachintha , Ades Alex , Nanayakkara Pavitra 
Published: December 2020

Importance
Cervical insufficiency (CI) is a serious complication of pregnancy, which can cause preterm birth. Identifying how to most effectively treat CI has the potential to maximize neonatal survival in this population of women.

Objective
To determine whether transabdominal cervical cerclage should be offered as a first-line treatment option in high-risk women.

Evidence Acquisition
An electronic literature search for relevant studies was conducted using keywords (CI, cervical cerclage) on the MEDLINE database.

Results
Although transabdominal cerclage (TAC) is reserved as a second-line treatment option over transvaginal cerclage (TVC), it has some advantages over TVC: a higher placement of the suture at the level of the cervicoisthmic junction; avoidance of placement of foreign material in the vagina, in turn, reducing risk of infection and inflammation, which can propagate preterm labor; and the option to leave the suture in place for future pregnancies. Systematic review evidence offers TAC as a more effective procedure to TVC in reducing preterm birth and maximizing neonatal survival. Although TAC is a slightly more complex procedure compared with TVC, advances in minimally invasive surgery now allow gynecologists to perform this more effective procedure laparoscopically and therefore without the added morbidity of open surgery but with the same if not better outcomes.

Conclusions
Laparoscopic TAC can provide a more effective treatment option for CI without the added burdens of open abdominal surgery.

Relevance
Our article highlights future directions for study in the area of cervical cerclage and refinement of existing practices.

Target Audience
Obstetricians and gynecologists, family physicians

Learning Objectives
After completing this activity, the learner should be better able to identify patients at high risk of CI; describe surgical management techniques for CI; and assess TAC, particularly a laparoscopic approach, as a first-line strategy for management of CI in high-risk groups.
Pseudopuniceibacterium antarcticum sp. nov., isolated from an Antarctic marine sponge
Authors: Liao Li , Su Shi-Yuan , Zhang Yan-Jiao , Liu Huan , Zhang Xi-Ying , Zhang Jin , Wen Jiao , Chen Bo , Yu Yong 
Published: December 2020

A Gram-negative, aerobic, rod-shaped, non-motile bacterium, designated strain HQ09T, was isolated from a marine sponge off the coast of Fields Peninsula, West Antarctica. Strain HQ09T grew at 4–35 °C (optimum, 25 °C), pH 5–9 (optimum, pH 7.0), and with 1–10% NaCl (optimum, 2 %). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain HQ09T was affiliated with the genus

Pseudopuniceibacterium

in the family

Rhodobacteraceae

, sharing 99.64 % identity with the type strain of

Pseudopuniceibacterium sediminis

, the only known species in the genus. However, the low digital DNA–DNA hybridization (dDDH) (27.2 %) and average nucleotide identity (ANI) (83.63 %) values between strain HQ09T and the type strain of

Pseudopuniceibacterium sediminis

indicated that they did not belong to the same species. Strain HQ09T could also be differentiated from

Pseudopuniceibacterium sediminis

by many phenotypic characteristics. The major fatty acids (>5 %) of strain HQ09T were summed feature 8 (C18 : 1
ω7c/C18 : 1 ω6c), 11-methyl C18 : 1
ω7c, C16 : 0 and C19 : 0 cyclo ω8c. The polar lipids included phosphatidylglycerol, phosphatidylcholine, two unidentified aminolipids and one unidentified phospholipid. The predominant respiratory quinone was ubiquinone 10 (Q-10). The genomic DNA G+C content was 62.63 mol%. Four secondary metabolite biosynthetic gene clusters were detected in the genome, potentially producing ectoine and three types of unknown compounds. On the basis of the polyphasic evidences obtained in this study, strain HQ09T represents a novel species of the genus

Pseudopuniceibacterium

, for which the name Pseudopuniceibacterium antarcticum sp. nov. is proposed, with the type strain being HQ09T (=KCTC 52229T=CGMCC 1.15538T).
Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability
Authors: Ding Bo , Liu Ying , Liu Zhiheng , Zheng Lina , Xu Ping , Chen Zhao , Wu Peiyao , Zhao Ying , Pan Qian , Guo Yu , Wei Wensheng , Wang Wei 
Published: December 2020

ABSTRACTThe majority of the non-coding regions in the human genome do not harbor any annotated element and are even not marked with any epigenomic signal or protein binding. An understudied aspect of these regions is their possible roles in stabilizing the 3D chromatin organization. To illuminate their “structural importance”, we chose to start with the non-coding regions forming many 3D contacts (referred to as hubs) and identified dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact gene expression located distal in the genome. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of the disease-associated genetic variations (GVs). Furthermore, our analyses also suggested a powerful approach to develop “one-drug-multiple-targets” therapeutics targeting the disease-specific non-coding regions.
Engineering clinically-approved drug gated CAR circuits
Authors: Li Hui-Shan , Wong Nicole M. , Tague Elliot , Ngo John T. , Khalil Ahmad S. , Wong Wilson W. 
Published: December 2020

SUMMARYChimeric antigen receptor (CAR) T cell immunotherapy has the potential to revolutionize cancer medicine. However, excessive CAR activation, lack of tumor-specific surface markers, and antigen escape have limited the safety and efficacy of CAR T cell therapy. A multi-antigen targeting CAR system that is regulated by safe,clinically-approvedpharmaceutical agents is urgently needed, yet only a few simple systems have been developed, and even fewer have been evaluated for efficacyin vivo. Here, we present NASCAR (NS3ASsociated CAR), a collection of induc-ible ON and OFF switch CAR circuits engineered with a NS3 protease domain deriving from the Hepatitis C Virus (HCV). We establish their ability to regulate CAR activity using multiple FDA-approved antiviral protease inhibitors, including grazoprevir (GZV), bothin vitroand in a xenograft tumor model. In addition, we have engineered several dual-gated NASCAR circuits, consisting of an AND logic gate CAR, universal ON-OFF CAR, and a switchboard CAR. These engineered receptors enhance control over T cell activity and tumor-targeting specificity. Together, our com-prehensive set of multiplex drug-gated CAR circuits represent a dynamic, tunable, and clinically-ready set of modules for enhancing the safety of CAR T cell therapy.
Epigenetic control of coordinated hematopoietic and cardiovascular development by Rnf2 in zebrafish
Authors: Peng XX , Feng G , Sun YH 
Published: December 2020

AbstractEarly embryogenesis requires the coordinated development of cardiovascular and hematopoietic lineages. However, the underlying cellular and genetic mechanisms are poorly understood. Here, we show that Rnf2, the core enzymatic component of Polycomb repressive complex 1 (PRC1), plays an important role in the control of cardiovascular and hematopoietic development and differentiation via suppressing the master hematoendothelial progenitor genes in zebrafish. In the absence of Rnf2, a group of transcription factor (TF) genes crucial for hematoendothelial specification such asetv2,gata2,lmo2andtal1are significantly up-regulated, which causes an expansion of hematopoietic and endothelial progenitors at the expense of myocardial differentiation, resulting in severe defects in both cardiogenesis and hematopoiesis. Although the number of hematopoietic stem cells (HSCs) is increased, both primitive and definitive waves of hematopoiesis are severely compromised inrnf2mutant embryos, suggesting that Rnf2 is required for differentiation of blood progenitor cells. Combined ChIP-seq and RNA-seq analysis shows that Rnf2 directly binds to key hematoendothelial progenitor genes and represses its expression. We further show that Rnf2-mediated gene repression depends on its H2Aub1 catalytic activity. We propose that PRC1/Rnf2-mediated epigenetic mechanism plays a key role in coordinated development of cardiovascular and hematopoietic lineages by repressing key hematoendothelial progenitor genes.HighlightsRnf2 is required for suppressing the expression of key hematoendothelial TF genes in precursors and its differentiated descendants.Rnf2 mutant zebrafish embryos display defective hematopoiesis and cardiogenesis.Loss of Rnf2 results in increased HSC numbers and arrested differentiation, hallmarks of leukemia.Rnf2 suppresses hematoendothelial progenitor genes via depositing H2Aub1.
Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation
Authors: Anand Gautam , Perry Alexandra M. , Cummings Celeste L. , Raymond Emma St. , Clemens Regina A. , Steed Ashley L. 
Published: December 2020

AbstractSARS-CoV-2, the virus that has caused the COVID-19 pandemic, robustly activates the host immune system in critically ill patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3, TBK1, and MYD88 while that of E is largely MYD88 independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation and pulmonary vasculitis in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation and their potential for therapeutic intervention.Author SummarySARS-CoV-2 robustly activates widespread inflammation, but we do not understand mechanistically how the virus engages the immune system. This knowledge will facilitate the development of critically needed therapeutic strategies to promote beneficial immune responses will dampening harmful inflammation. Here we demonstrate that SARS-CoV-2 surface proteins spike and envelope alone activated innate cell function and the interferon signaling pathway. This activation occurred in both immune and epithelial cells, and mechanistic studies demonstrated dependence on known key inflammatory signaling mediators, IRF3, TBK1, and MYD88. In animal studies, we showed that these viral surface proteins induce epithelial cell IFN-dependent lung pathology, reminiscent to acute COVID-19 pulmonary infection. These findings underscore the need for further investigation into the role of SARS-CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation.
Stepwise gating of the Sec61 protein-conducting channel by Sec63 and Sec62
Authors: Itskanov Samuel , Park Eunyong 
Published: December 2020

SummaryThe universally conserved Sec61/SecY channel mediates transport of many newly synthesized polypeptides across membranes, an essential step in protein secretion and membrane protein integration1-5. The channel has two gating mechanisms—a lipid-facing lateral gate, through which hydrophobic signal sequences or transmembrane helices (TMs) are released into the membrane, and a vertical gate, called the plug, which regulates the water-filled pore required for translocation of hydrophilic polypeptide segments6. Currently, how these gates are controlled and how they regulate the translocation process remain poorly understood. Here, by analyzing cryo-electron microscopy (cryo-EM) structures of several variants of the eukaryotic post-translational translocation complex Sec61-Sec62-Sec63, we reveal discrete gating steps of Sec61 and the mechanism by which Sec62 and Sec63 induce these gating events. We show that Sec62 forms a V-shaped structure in front of the lateral gate to fully open both gates of Sec61. Without Sec62, the lateral gate opening narrows, and the vertical pore becomes closed by the plug, rendering the channel inactive. We further show that the lateral gate is opened first by interactions between Sec61 and Sec63 in both cytosolic and luminal domains, a simultaneous disruption of which fully closes the channel. Our study defines the function of Sec62 and illuminates how Sec63 and Sec62 work together in a hierarchical manner to activate the Sec61 channel for post-translational translocation.
Jumping over Baselines with New Methods to Predict Activation Maps from Resting-state fMRI
Authors: Lacosse Eric , Scheffler Klaus , Lohmann Gabriele , Martius Georg 
Published: December 2020

ABSTRACTCognitive fMRI research primarily relies on task-averaged responses over many subjects to describe general principles of brain function. Nonetheless, there exists a large variability between subjects that is also reflected in spontaneous brain activity as measured by resting state fMRI (rsfMRI). Leveraging this fact, several recent studies have therefore aimed at predicting task activation from rsfMRI using various machine learning methods within a growing literature on ‘connectome fingerprinting.’ In reviewing these results, we found lack of an evaluation against robust baselines that reliably supports a novelty of predictions for this task. On closer examination to reported methods, we found most underperform against trivial baseline model performances based on massive group averaging when whole-cortex prediction is considered. Here we present a modification to published methods that remedies this problem to large extent. Our proposed modification is based on a single-vertex approach that replaces commonly used brain parcellations. We further provide a summary of this model evaluation by characterizing empirical properties of where prediction for this task appears possible, explaining why some predictions largely fail for certain targets. Finally, with these empirical observations we investigate whether individual prediction scores explain individual behavioral differences in a task.
Predictive modeling of long non-coding RNA chromatin (dis-)association
Authors: Ntini Evgenia , Budach Stefan , Vang Ørom Ulf A , Marsico Annalisa 
Published: December 2020

SummaryLong non-coding RNAs (lncRNAs) are involved in gene expression regulation incisandtrans. Although enriched in the chromatin cell fraction, to what degree this defines their broad range of functions remains unclear. In addition, the factors that contribute to lncRNA chromatin tethering, as well as the molecular basis of efficient lncRNA chromatin dissociation and its functional impact on enhancer activity and target gene expression, remain to be resolved. Here, we combine pulse-chase metabolic labeling of nascent RNA with chromatin fractionation and transient transcriptome sequencing to follow nascent RNA transcripts from their co-transcriptional state to their release into the nucleoplasm. By incorporating functional and physical characteristics in machine learning models, we find that parameters like co-transcriptional splicing contributes to efficient lncRNA chromatin dissociation. Intriguingly, lncRNAs transcribed from enhancer-like regions display reduced chromatin retention, suggesting that, in addition to splicing, lncRNA chromatin dissociation may contribute to enhancer activity and target gene expression.HighlightsChromatin (dis-)association of lncRNAs can be modeled using nascent RNA sequencing from pulse-chase chromatin fractionationDistinct physical and functional characteristics contribute to lncRNA chromatin (dis-)associationlncRNAs transcribed from enhancers display increased degree of chromatin dissociationlncRNAs of distinct degrees of chromatin association display differential binding probabilities for RNA-binding proteins (RBPs)
A functional artificial neural network for noninvasive presurgical evaluation of glioblastoma multiforme prognosis and radiosensitivity profiling
Authors: Zander Eric , Ardeleanu Andrew , Singleton Ryan , Bede Barnabas , Wu Yilin , Zheng Shuhua 
Published: December 2020

AbstractBackground and PurposeGenetic profiling for glioblastoma multiforme (GBM) patients with intracranial biopsy carries a significant risk of permanent morbidity. We previously demonstrated that theCUL2gene, encoding the scaffold cullin2 protein in the cullin2-RING E3 ligase (CRL2), can predict GBM radiosensitivity and prognosis mainly due to the functional involvement of CRL2 in mediating hypoxia-inducible factor 1 (HIF-1) α and epidermal growth factor receptor (EGFR) degradation. BecauseCUL2expression levels are closely regulated with its copy number variations (CNVs), this study aims to develop an artificial neural network (ANN) that can predict GBM prognosis and help optimize personalized GBM treatment planning.Materials and MethodsDatasets including Ivy-GAP, The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM), the Chinese Glioma Genome Atlas (CGGA) were analyzed. T1 images from corresponding cases were studied using automated segmentation for features of heterogeneity and tumor edge contouring.ResultsWe developed a 4-layer neural network that can consistently predict GBM prognosis with 80-85% accuracy with 3 inputs includingCUL2copy number, patient’s age at GBM diagnosis, and surface vs. volume (SvV) ratio.ConclusionA functional 4-layer neural network was constructed that can predict GBM prognosis and potential radiosensitivity.
Resting-state functional connectivity and psychopathology in Klinefelter syndrome (47, XXY)
Authors: Whitman Ethan T. , Liu Siyuan , Torres Erin , Warling Allysa , Wilson Kathleen , Nadig Ajay , McDermott Cassidy , Clasen Liv S. , Blumenthal Jonathan D. , Lalonde François M. , Gotts Stephen J. , Martin Alex , Raznahan Armin 
Published: December 2020

ABSTRACTKlinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collected resting state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males. We implemented a brain-wide screen to identify regions with altered global rsFC in XXY vs. XY males, and then used seed-based analysis to decompose these alterations. We further compared rsFC changes with regional changes in brain volume from voxel-based morphometry and tested for correlations between rsFC and symptom variation within XXY syndrome. We found that XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC), associated with overconnectivity with diverse rsFC networks. Regional rsFC changes were partly coupled to regional volumetric changes in XXY syndrome. Within the precuneus, variation in DLPFC rsFC within XXY syndrome was correlated with the severity of psychopathology in XXY individuals. Our findings provide the first view of altered functional brain connectivity in XXY syndrome and delineate links between these alterations and those relating to both brain anatomy and psychopathology. Taken together, these insights advance biological understanding of XXY syndrome as a disorder in its own right, and as a model of genetic risk for psychopathology more broadly.