bluuebunny/crossref_metadata_2025_split huggingface dataset:
STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and S-Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma
Authors: Koenig Michael J. , Agana Bernice A. , Kaufman Jacob M. , Sharpnack Michael F. , Wang Walter Z. , Weigel Christoph , Navarro Fabio C.P. , Amann Joseph M. , Cacciato Nicole , Arasada Rajeswara Rao , Gerstein Mark B. , Wysocki Vicki H. , Oakes Christopher , Carbone David P. 
Published: May 2021

Abstract

STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation. LKB1-deficient tumors showed depletion of S-adenosyl-methionine (SAM-e), which is the primary substrate for DNMT1 activity. Lower methylation following LKB1 loss involved repetitive elements (RE) and altered RE transcription, as well as decreased sensitivity to azacytidine. Demethylated CpGs were enriched for FOXA family consensus binding sites, and nuclear expression, localization, and turnover of FOXA was dependent upon LKB1. Overall, these findings demonstrate that a large number of lung adenocarcinomas exhibit global hypomethylation driven by LKB1 loss, which has implications for both epigenetic therapy and immunotherapy in these cancers.

Significance:
Lung adenocarcinomas with LKB1 loss demonstrate global genomic hypomethylation associated with depletion of SAM-e, reduced expression of DNMT1, and increased transcription of repetitive elements.
Oncolytic Vaccinia Virus Gene Modification and Cytokine Expression Effects on Tumor Infection, Immune Response, and Killing
Authors: Inoue Tomoyoshi , Byrne Thomas , Inoue Mitsuko , Tait Madeline E. , Wall Patrick , Wang Annabel , Dermyer Michael R. , Laklai Hanane , Binder Joseph J. , Lees Clare , Hollingsworth Robert , Maruri-Avidal Liliana , Kirn David H. , McDonald Donald M. 
Published: May 2021

Abstract
Oncolytic vaccinia viruses have promising efficacy and safety profiles in cancer therapy. Although antitumor activity can be increased by manipulating viral genes, the relative efficacy of individual modifications has been difficult to assess without side-by-side comparisons. This study sought to compare the initial antitumor activity after intravenous administration of five vaccinia virus variants of the same Western Reserve backbone and thymidine kinase gene deletion in RIP-Tag2 transgenic mice with spontaneous pancreatic neuroendocrine tumors. Tumors had focal regions of infection at 5 days after all viruses. Natural killer (NK) cells were restricted to these sites of infection, but CD8+ T cells and tumor cell apoptosis were widespread and varied among the viruses. Antitumor activity of virus VV-A34, bearing amino acid substitution A34K151E to increase viral spreading, and virus VV-IL2v, expressing a mouse IL2 variant (mIL2v) with attenuated IL2 receptor alpha subunit binding, was similar to control virus VV-GFP. However, antitumor activity was significantly greater after virus VV-A34/IL2v, which expressed mIL2v together with A34K151E mutation and viral B18R gene deletion, and virus VV-GMCSF that expressed mouse GM-CSF. Both viruses greatly increased expression of CD8 antigens Cd8a/Cd8b1 and cytotoxicity genes granzyme A, granzyme B, Fas ligand, and perforin-1 in tumors. VV-A34/IL2v led to higher serum IL2 and greater tumor expression of death receptor ligand TRAIL, but VV-GMCSF led to higher serum GM-CSF, greater expression of leukocyte chemokines and adhesion molecules, and more neutrophil recruitment. Together, the results show that antitumor activity is similarly increased by viral expression of GM-CSF or IL2v combined with additional genetic modifications.
Targeting Solid Tumors Using CD3 Bispecific Antibodies
Authors: Crawford Alison , Chiu Danica 
Published: May 2021

Abstract
Immunotherapies to treat cancer have made tremendous progress over the past decade. In particular, T cell–directed therapies have gained considerable attention with CD3 bispecific antibodies and CAR T cells showing potent responses against hematologic tumors. At present, the ability to adapt these therapeutics to treat solid tumors is less established. Herein, we discuss recent advances in T cell–engaging CD3 bispecific antibodies targeting solid tumors, potential mechanisms of resistance, and future prospects. A better understanding of the mechanisms of immune evasion in solid tumors will enable the development of strategies to overcome this resistance and inform choices of therapeutic combinations.
Associação entre a classificação da deambulação funcional com a velocidade da marcha após acidente vascular cerebral
Authors: Júlio Cíntia Elord , Cardoso Ariadne , Pereira Gabriela Santos , Corrêa João Carlos Ferrari , Silva Soraia Micaela 
Published: May 2021

The choice of the appropriate instrument is decisive for the success of functional assessment and rehabilitation. In view of this, it is necessary that the professional has extensive knowledge of the instruments available so that he can choose the most effective, least costly and quickest assessment. Objective: To analyze whether the classification of ambulation obtained by the Functional Ambulation Classification (FAC) is associated with the performance obtained in the 10-meter walk test (TC10m). Methods: Cross-sectional study in which 61 individuals affected by stroke were evaluated. TC10m and FAC were used. To verify the normality of the data, a Kolmogorov-Smirnov test was used. One-way ANOVA was used to check whether there was a difference between dependent and independent walkers according to FAC with gait speed using the TC10m. A post hoc test and the Scheffe method were performed, considering p≤0.05. To analyze the association between the categorization of walking and gait speed, the chi-square test of independence was used. Results: There was a significant difference at each FAC level in relation to gait speed. There was an association between the classifications obtained by the FAC and by the TC10m [x2(9) = 145.335; p= 0.001]; and in 48% the variables are correctly associated. Conclusion: The findings indicated that the FAC levels were associated with walking speed. This finding expands the knowledge about gait assessment measures and helps clinical practice, considering that it facilitates the choice of the best instrument to assess gait after stroke.
Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure
Authors: Kar Saibal , Mack Michael J. , Lindenfeld JoAnn , Abraham William T. , Asch Federico M. , Weissman Neil J. , Enriquez-Sarano Maurice , Lim D. Scott , Mishell Jacob M. , Whisenant Brian K. , Rogers Jason H. , Arnold Suzanne V. , Cohen David J. , Grayburn Paul A. , Stone Gregg W. 
Published: May 2021

Background:
In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone.

Methods:
Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days.

Results:

TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [
P
<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [
P
<0.0001]). This relationship was consistent in the TMVr and GDMT arms (
P
interaction
=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (–0.3±1.7 versus –9.4±4.6 [
P
=0.0008]) consistently in both groups (
P
interaction
=0.95).

Conclusions:
In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01626079.
Complications Associated With Catheter Ablation in Patients With Atrial Fibrillation: A Report From the JROAD‐DPC Study
Authors: Yokoyama Yasuhiro , Miyamoto Koji , Nakai Michikazu , Sumita Yoko , Ueda Nobuhiko , Nakajima Kenzaburo , Kamakura Tsukasa , Wada Mitsuru , Yamagata Kenichiro , Ishibashi Kohei , Inoue Yuko , Nagase Satoshi , Noda Takashi , Aiba Takeshi , Miyamoto Yoshihiro , Yasuda Satoshi , Kusano Kengo 
Published: May 2021

Background
Aging is one of the major concerns and determinants of the indications for catheter ablation (CA) for atrial fibrillation. This study aimed to assess the safety of CA in older patients with atrial fibrillation undergoing CA.

Methods and Results
The JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases‐Diagnosis Procedure Combination) is a nationwide claims database using data from the Japanese Diagnosis Procedure Combination/Per Diem Payment System. Among 6 632 484 records found between April 2012 and March 2018 from 1058 hospitals, 135 299 patients with atrial fibrillation (aged 65±10 years, 38 952 women) who underwent CA in 456 hospitals were studied and divided into the following age groups: <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, 80 to 84, and ≥85 years. The overall in‐hospital complication rate was 3.4% (cardiac tamponade 1.2%), and in‐hospital mortality was 0.04%. Older patients had a higher prevalence of women, lower body mass index, and a higher burden of comorbidities such as hypertension, and all of those characteristics were predictors for complications in multivariate analysis. A multivariate adjusted odds ratio revealed that increased age was independently and significantly associated with overall complications (60–64 years, 1.19; 65–69 years, 1.29; 70–74 years, 1.57; 75–79 years, 1.63; 80–84 years, 1.90; and ≥85 years, 2.86; the reference was <60 years).

Conclusions
The nationwide JROAD‐DPC database demonstrated that the frequency of complications following CA in patients with atrial fibrillation increased according to age.
Association Between Omega‐3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA
Authors: Kapoor Karan , Alfaddagh Abdulhamied , Al Rifai Mahmoud , Bhatt Deepak L. , Budoff Matthew J. , Nasir Khurram , Miller Michael , Welty Francine K. , McEvoy J. William , Dardari Zeina , Shapiro Michael D. , Blumenthal Roger S. , Tsai Michael Y. , Blaha Michael J. 
Published: May 2021

Background
Randomized trials of pharmacologic strength omega‐3 fatty acid (n3‐FA)–based therapies suggest a dose‐dependent cardiovascular benefit. Whether blood n3‐FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3‐FA levels would be associated with incident bleeding and AF events in MESA (Multi‐Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline.

Methods and Results

We examined the association between baseline plasma n3‐FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization
International Classification of Diseases, Ninth Revision
(
ICD‐9
), and
International Classification of Diseases, Tenth Revision
(
ICD‐10
), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3‐FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA.

Conclusions
In MESA, higher plasma levels of n3‐FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.
Alarm calls of house wrens (Troglodytes aedon bonariae) elicit responses of conspecific and heterospecific species
Authors: Carro Mariana E. , Fernández Gustavo J. 
Published: May 2021

Abstract
Nesting house wrens (Troglodytes aedon bonariae) use two basic alarm calls (Type I and Type II) when detect a threat near the nest. We experimentally analysed if calls distract predators or serve to recruit other birds to create a mobbing flock to deter predators. The results show that individuals preferentially position themselves in front of the threat, disclosing the location of the nest. Also, using playbacks of house wren alarm calls we found that these calls recruited both conspecific and heterospecific individuals to create a mobbing response. The alarm calls of house wrens seem to fulfil multiple functions, not only conveying information about the threat to their mates and nestling as revealed in previous studies, but also as a signal that attracts the attention of other conspecific and heterospecific individuals and can trigger a mobbing response to deter the predator.
Struggles of Delivery Workers in Brazil: Working Conditions and Collective Organization during the Pandemic
Authors: Abilio Ludmila Costhek , Grohmann Rafael , Weiss Henrique Chevrand 
Published: May 2021

Abstract
This article aims to analyze food delivery workers’ working conditions and ongoing collective organization during the pandemic in Brazil. The discussion involves historical analysis, based on empirical research carried out with delivery couriers over the past eight years in Brazil and on analysis of the delivery workers’ strikes in July of 2020. Our view is that their work is subsumed to a new type of work organization, management and control, defined here as uberization. Recent investigation shows that their working conditions are worsening during the Covid-19 pandemic in terms of reduced working hour value alongside unchangingly long workdays. These conditions have been met by platform workers’ collective organizations demanding better working conditions. Our findings indicate an ongoing political struggle involving different institutions, and the central role of communication between workers through digital platforms as the first form of organization. From the class composition framework, we understand that there is a germ for political composition involving Brazilian riders, in line with the circulation of workers’ struggles around the world, especially in Latin America.
Benchmarking performance changes in the simulation of extratropical modes of variability across CMIP generations
Authors: Lee Jiwoo , Sperber Kenneth R. , Gleckler Peter J. , Taylor Karl E. , Bonfils Céline J. W. 
Published: May 2021

AbstractWe evaluate extratropical modes of variability in the three most recent phases of the Coupled Model Intercomparison Project (CMIP3, 5, and 6) to gauge improvement of climate models over time. A suite of high-level metrics is employed to objectively evaluate how well climate models simulate the qobserved Northern Annular Mode (NAM), North Atlantic Oscillation (NAO), Pacific North America pattern (PNA), Southern Annular Mode (SAM), Pacific Decadal Oscillation (PDO), North Pacific Oscillation (NPO), and North Pacific Gyre Oscillation (NPGO). We apply a Common Basis Function (CBF) approach that projects model anomalies onto observed empirical orthogonal functions (EOFs), together with the traditional EOF approach, to CMIP Historical and AMIP models. We find simulated spatial patterns of those modes have been significantly improved in the newer models, although the skill improvement is sensitive to the mode and season considered. We identify some potential contributions to the pattern improvement of certain modes (e.g., the Southern Hemisphere jet and High-top vertical coordinate), however the performance changes are likely attributed to gradual improvement of the base climate and multiple relevant processes. Less performance improvement is evident in the mode amplitude of these modes and systematic overestimation of the mode amplitude in spring remains in the newer climate models. We find that the post-dominant season amplitude errors in atmospheric modes are not limited to coupled runs but are often already evident in AMIP simulations. This suggests that rectifying the egregious post-dominant season amplitude errors found in many models can be addressed in an atmospheric-only framework making it more tractable to address in the model development process.
The Effects of Stress on Tourniquet Application and CPR Performance in Layperson and Professional Civilian Populations
Authors: Friberg Marc , Jonson Carl-Oscar , Jaeger Victor , Prytz Erik 
Published: May 2021

Objective The purpose of this study was to compare laypeople’s and professional first responders’ ability to perform tourniquet application and cardiopulmonary resuscitation (CPR) during calm and stressful circumstances. Background Life-threatening bleeding is a major cause of death that could be prevented by fast and appropriate first aid interventions. Therefore, laypeople are now being trained in bleeding control skills, transforming them from bystanders to immediate responders. However, critics have questioned whether laypeople are able to perform during more stressful conditions. Method Twenty-four laypersons and 31 professional first responders were tested in two conditions: a calm classroom scenario and a stressful scenario consisting of paintball fire and physical exertion. Stress and workload were assessed along with task performance. Results The experimental manipulation was successful in terms of eliciting stress reactions. Tourniquet application performance did not decline in the stressful condition, but some aspects of CPR performance did for both groups. First responders experienced higher task engagement and lower distress, worry and workload than the laypeople in both the calm and stressful conditions. Conclusion Stress did not affect first responders and laypeople differently in terms of performance effects. Stress should therefore not be considered a major obstacle for teaching bleeding control skills to laypeople. Application Tourniquet application can be taught to laypeople in a short amount of time, and they can perform this skill during stress in controlled settings. Concerns about laypeople’s ability to perform under stress should not exclude bleeding control skills from first aid courses for civilian laypeople.
Serum CA125 a potential marker of volume status for peritoneal dialysis patients?
Authors: Wijayaratne Dilushi , Muthuppalaniappan Vasantha Muthu , Davenport Andrew 
Published: May 2021

Introduction: Serum cancer antigen 125(SeCA125) has been reported to be increased in patients with heart failure and correlate with both extracellular water (ECW) overload and poor prognosis. Ultrafiltration failure and ECW overload are a major cause of peritoneal dialysis (PD) technique failure. We wished to determine whether SeCA125 could also be a marker of volume status in PD patients. Methods: We contemporaneously measured SeCA125, serum N terminal brain natriuretic peptide (NTproBNP) and ECW by bioimpedance in adult PD patients attending for outpatient assessment of peritoneal membrane function. Results: The median SeCA125 was 19 (12–33) U/mL in 489 PD patients, 61.3% male, median age 61.5 (interquartile range 50–75) years. SeCA125 was positively associated with the ratio of ECW/total body water (TBW) ( r = 0.29, p < 0.001), 4-h peritoneal dialysate to serum creatinine ratio ( r = 0.23, p < 0.001), NTproBNP) ( r = 0.18, p < 0.001), and age ( r = 00.17, p = 0.001) and negatively with 24-h PD ultrafiltration volume ( r = −0.28, p < 0.001) serum albumin ( r = −0.22, p < 0.001), and echocardiographic left ventricular ejection fraction ( r = −0.20, p < 0.001), but not with residual renal function or C-reactive protein. Patients with above the median SeCA125, had greater median ECW/TBW 0.403(IQR 0.394–0.410) vs 0.395(0.387–0.404), p < 0.001 and NTproBNP (6870 (IQR 1936–20096) vs 4069 (1345–12291) vs) pg/mL, p = 0.03. Conclusion: Heart failure studies have reported SeCA125 is a marker of ECW overload. Our retrospective analysis suggests that SeCA125 is also associated with ECW volume in PD patients. Further studies are required to determine whether serial measurements of SeCA125 trend with changes in ECW status in PD patients and can be used to aid volume assessments.
The broadening boundaries of materialism
Authors: Atanasova Aleksandrina , Eckhardt Giana M. 
Published: May 2021

The implications of waning desire for ownership on materialism are not well understood. This study examines the interface between materialism and consumption and asks, is materialism manifest in the absence of ownership centrality, and if so, how? Drawing from an interpretive investigation of digital nomads, it is suggested that materialism has broadened to adapt to non-ownership centrality, and we define it as a logic of consumption, which manifests as a preoccupation with the consumption of objects, access or experiences as a way to signal status, build image, pursue happiness, and attain a sense of self-worth. Three discrete but complementary ways through which materialism emerges in the absence of ownership centrality are identified: (1) preoccupation with strategic curation rather than accumulation, (2) intentional prioritization of experiential consumption over ownership as a means to fulfill materialistic aims, and (3) adoption of bricolages across spectrums of consumption (solid/liquid, budget/luxury, access/ownership).