bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X7 Receptor Activity Limits Accumulation of T Cells within Tumors
Authors: Romagnani Andrea , Rottoli Elsa , Mazza Emilia Maria Cristina , Rezzonico-Jost Tanja , De Ponte Conti Benedetta , Proietti Michele , Perotti Michela , Civanelli Elisa , Perruzza Lisa , Catapano Alberico L. , Baragetti Andrea , Tenedini Elena , Tagliafico Enrico , Falzoni Simonetta , Di Virgilio Francesco , Norata Giuseppe Danilo , Bicciato Silvio , Grassi Fabio 
Published: July 2020

AbstractExtracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A (Cdkn1a, encoding for p21Waf1/Cip1). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies.Significance:These findings suggest that the purinergic checkpoint P2X7 may be targeted to enhance T-cell–mediated cancer immunotherapy and improve T effector cell accumulation in the tumor microenvironment.
Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy
Authors: Nowicki Theodore S. , Farrell Colin , Morselli Marco , Rubbi Liudmilla , Campbell Katie M. , Macabali Mignonette H. , Berent-Maoz Beata , Comin-Anduix Begoña , Pellegrini Matteo , Ribas Antoni 
Published: July 2020

Abstract

Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) γ-retroviral vectors. Analysis of clinical transgenic adoptive cell therapy products in vivo revealed that despite strong persistence of the transgenic TCR DNA sequence over time, its expression was profoundly decreased over time at the RNA and protein levels. Patients with the greatest degrees of expression suppression displayed significant increases in DNA methylation over time within the MSCV promoter region, as well as progressive increases in DNA methylation within the entire MSCV vector over time. These increases in vector methylation occurred independently of its integration site within the host genomes. These results have significant implications for the design of future viral vector gene–engineered adoptive cell transfer therapies.

Significance:
Cellular immunotherapies' reliance on retroviral vectors encoding foreign genetic material can be vulnerable to progressive acquisition of DNA methylation and subsequent epigenetic suppression of the transgenic product in TCR adoptive cell therapy. This must be considered in the design of future generations of cellular immunotherapies for cancer.
This article is highlighted in the In This Issue feature, p. 1611
Effects of Sugar‐Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial
Authors: Ebbeling Cara B. , Feldman Henry A. , Steltz Sarah K. , Quinn Nicolle L. , Robinson Lisa M. , Ludwig David S. 
Published: July 2020

Background
A 2018 American Heart Association science advisory indicated that, pending further research, artificially sweetened beverages (ASBs) may be an appropriate initial replacement for sugar‐sweetened beverages (SSBs) during transition to unsweetened beverages (USBs).

Methods and Results

We randomly assigned 203 adults (121 males, 82 females; 91.6% retention), who habitually consumed SSBs, to 3 groups and delivered free SSBs, ASBs, or USBs to their homes for 12 months. Outcomes included serum triglyceride to high‐density lipoprotein cholesterol ratio (primary), body weight, and sweet taste preference (experimental assessment, 0%–18% sucrose solutions). Change in serum triglyceride to high‐density lipoprotein cholesterol ratio was not different between groups. Although overall change in weight also was not different between groups, we found effect modification (
P
=0.006) by central adiposity. Among participants in the highest tertile of baseline trunk fat but not other tertiles, weight gain was greater (
P
=0.002) for the SSB (4.4±1.0 kg, estimate±SE) compared with ASB (0.5±0.9 kg) or USB (−0.2±0.9 kg) group. Both sweetness threshold (–1.0±0.2% m/v;
P
=0.005) and favorite concentration (–2.3±0.4% m/v;
P
<0.0001) decreased in the USB group; neither changed in the SSB group. In the ASB group, sweetness threshold did not change, and favorite concentration decreased (–1.1±0.5% m/v;
P
=0.02). Pairwise comparison between the ASB and USB groups indicated a difference in sweetness threshold (
P
=0.015).

Conclusions
Replacing SSBs with noncaloric beverages for 12 months did not affect serum triglyceride to high‐density lipoprotein cholesterol ratio. Among individuals with central adiposity, replacing SSBs with either ASBs or USBs lowered body weight. However, USBs may have the most favorable effect on sweet taste preference.

Registration

URL:
https://www.clinicaltrials.gov
; unique identifier: NCT01295671.
Dismal Outcomes and High Societal Burden of Mitral Valve Regurgitation in France in the Recent Era: A Nationwide Perspective
Authors: Messika‐Zeitoun David , Candolfi Pascal , Vahanian Alec , Chan Vincent , Burwash Ian G. , Philippon Jean‐François , Toussaint Jean‐Manuel , Verta Patrick , Feldman Ted E. , Iung Bernard , Glineur David , Mesana Thierry , Enriquez‐Sarano Maurice 
Published: July 2020

Background
Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population‐based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level.

Methods and Results
In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In‐hospital and 1‐year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1‐year mortality or all‐cause readmission and 1‐year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively.

Conclusions
At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390–615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.
Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke
Authors: Keene Keith L. , Hyacinth Hyacinth I. , Bis Joshua C. , Kittner Steven J. , Mitchell Braxton D. , Cheng Yu-Ching , Pare Guillaume , Chong Michael , O’Donnell Martin , Meschia James F. , Chen Wei-Min , Sale Michèle M. , Rich Stephen S. , Nalls Mike A. , Zonderman Alan B. , Evans Michele K. , Wilson James G. , Correa Adolfo , Markus Hugh S. , Traylor Matthew , Lewis Cathryn M. , Carty Cara L. , Reiner Alexander , Haessler Jeff , Langefeld Carl D. , Gottesman Rebecca , Mosley Thomas H. , Woo Daniel , Yaffe Kristine , Liu YongMei , Longstreth William T. , Psaty Bruce M. , Kooperberg Charles , Lange Leslie A. , Sacco Ralph , Rundek Tatjana , Lee Jin-Moo , Cruchaga Carlos , Furie Karen L. , Arnett Donna K. , Benavente Oscar R. , Grewal Raji P. , Peddareddygari Leema Reddy , Dichgans Martin , Malik Rainer , Worrall Bradford B. , Fornage Myriam ,   on behalf of the COMPASS, SiGN, and METASTROKE Consortia
Published: July 2020

Background and Purpose:
Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.

Methods:
The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.

Results:

In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the
HNF1A
gene that reached genome-wide significance (
P
=4.62×10
−8
) and an additional 29 variants with suggestive evidence of association (
P
<1×10
−6
), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction
P
value of 2.08×10
−3
(0.05/24 unique loci), we were able to validate associations at the
HNF1A
locus in both SiGN (
P
=8.18×10
−4
) and METASTROKE (
P
=1.72×10
−3
) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the
HNF1A
gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the
SFXN4
and
TMEM108
genes represent potential novel ischemic stroke loci.

Conclusions:
These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.
Home range and habitat use of two sympatric crocodylians (Melanosuchus niger and Caiman yacare) under changing habitat conditions
Authors: De la Quintana Paola , Aparicio James , Pacheco Luis F. 
Published: July 2020

Abstract
We used radio-telemetry to record how Caiman yacare (Cy) and Melanosuchus niger (Mn) responded to the intrusion of the Maniqui river into Cedral Lagoon in the Bolivian Amazon. Nine M. niger and 3 C. yacare were followed between December 2015 and May 2016. Both species showed a gradual reduction in mean monthly range from December (19.96 ha Mn and 1.74 ha Cy) to May 2016 (0.08 ha Mn and 0.24 ha Cy). Habitat use was fairly constant throughout the months for both species, Melanosuchus niger used mainly open swampy forests and Cyperaceae Marshes, while C. yacare used more islands and flooded grasslands. This study shows that both species of caimans responded to changes in depth and vegetation types, as their habitat as a whole was changed by river intrusion.
Breaking the Spell: Reconsidering Cognitive and Evolutionary Approaches to Atheism
Authors: Szocik Konrad , Messick Kyle J. 
Published: July 2020

Abstract
The scientific study of nonreligion has been described as being ‘under the spell’ of religion because the vast majority of research investigates nonbelief in respect to belief. This has resulted in a number of problematic theories, including the leading cognitive science of religion (CSR) theory that claims that religious belief is innate, and so to be a nonbeliever is to violate cognitive predispositions. This article critically analyzes innateness theories and encourages the development of further theories that incorporate social, adaptive, cultural, evolutionary, and biological factors in addition to cognitive contributors. This article details the roles of adaptive and functional aspects of nonbelief, the influence of credibility enhancing displays (CRED s), and the influence of cultural context on nonbelief as they are not sufficiently explained by CSR theories. It is proposed that future theories study nonreligion in its own right, instead of respective to religion, so that a broader range of unique characteristics can be accounted for without inaccurately and inadequately phrasing theories in terms of naturalness.
A Hail Growth Trajectory Model for Exploring the Environmental Controls on Hail Size: Model Physics and Idealized Tests
Authors: Kumjian Matthew R. , Lombardo Kelly 
Published: July 2020

AbstractA detailed microphysical model of hail growth is developed and applied to idealized numerical simulations of deep convective storms. Hailstone embryos of various sizes and densities may be initialized in and around the simulated convective storm updraft, and then are tracked as they are advected and grow through various microphysical processes. Application to an idealized squall line and supercell storm results in a plausibly realistic distribution of maximum hailstone sizes for each. Simulated hail growth trajectories through idealized supercell storms exhibit many consistencies with previous hail trajectory work that used observed storms. Systematic tests of uncertain model parameters and parameterizations are performed, with results highlighting the sensitivity of hail size distributions to these changes. A set of idealized simulations is performed for supercells in environments with varying vertical wind shear to extend and clarify our prior work. The trajectory calculations reveal that, with increased zonal deep-layer shear, broader updrafts lead to increased residence time and thus larger maximum hail sizes. For cases with increased meridional low-level shear, updraft width is also increased, but hailstone sizes are smaller. This is a result of decreased residence time in the updraft, owing to faster northward flow within the updraft that advects hailstones through the growth region more rapidly. The results suggest that environments leading to weakened horizontal flow within supercell updrafts may lead to larger maximum hailstone sizes.
Vertical Structure of the Upper–Indian Ocean Thermal Variability
Authors: Li Yuanlong , Han Weiqing , Wang Fan , Zhang Lei , Duan Jing 
Published: July 2020

AbstractMulti-time-scale variabilities of the Indian Ocean (IO) temperature over 0–700 m are revisited from the perspective of vertical structure. Analysis of historical data for 1955–2018 identifies two dominant types of vertical structures that account for respectively 70.5% and 21.2% of the total variance on interannual-to-interdecadal time scales with the linear trend and seasonal cycle removed. The leading type manifests as vertically coherent warming/cooling with the maximal amplitude at ~100 m and exhibits evident interdecadal variations. The second type shows a vertical dipole structure between the surface (0–60 m) and subsurface (60–400 m) layers and interannual-to-decadal fluctuations. Ocean model experiments were performed to gain insights into underlying processes. The vertically coherent, basinwide warming/cooling of the IO on an interdecadal time scale is caused by changes of the Indonesian Throughflow (ITF) controlled by Pacific climate and anomalous surface heat fluxes partly originating from external forcing. Enhanced changes in the subtropical southern IO arise from positive air–sea feedback among sea surface temperature, winds, turbulent heat flux, cloud cover, and shortwave radiation. Regarding dipole-type variability, the basinwide surface warming is induced by surface heat flux forcing, and the subsurface cooling occurs only in the eastern IO. The cooling in the southeast IO is generated by the weakened ITF, whereas that in the northeast IO is caused by equatorial easterly winds through upwelling oceanic waves. Both El Niño–Southern Oscillation (ENSO) and IO dipole (IOD) events are favorable for the generation of such vertical dipole anomalies.
A Prospective Randomized Trial of N-butyl-cyanoacrylate + Metacryloxysulfolane Adhesive versus Suture Alone for Grafting in Rhinoplasty: 9 year Follow-up
Authors: Martino Carmine , Salzano Francesco , Martino Diletta , Ralli Massimo , De Vincentiis Marco , Maranzano Massimo , Greco Antonio , Salzano Giovanni , Di Stadio Arianna 
Published: July 2020

Objective: Use of cyanoacrylate glue in facial plastic surgery is still controversial due to the absence of long-term follow up showing the results. Aim of our study is comparing the long-term outcomes of N-butyl-cyanoacrylate + Metacryloxysulfolane versus traditional sutures in rhinoplasty. Methods: Prospective comparative study. One hundred forty-two patients affected by ptotic nasal tip were included and randomized in two groups. In group A, the surgeon fixed the graft by using the glue and suture and in group B by using the traditional suture only. The following data were collected and compared by statistical analysis: nasolabial angle before and after surgery, dimensions of the graft, duration time (in minutes) for graft application during the surgery, number of sutures applied to fix the graft, presence of post-surgery negative outcomes. Results: All patients statistically improved their nasolabial angle after surgery (ANOVA: P < .0001) without statistically significant differences between the two groups both at short and long follow-up (χ: P = 1 and P = .9 respectively). A statistically significant difference in graft fixation time ( P < .00001) and number of sutures (t: P < .00001) used was observed between the two groups. No statistically significant difference was observed in prevalence of infection after surgery. Conclusion: N-butyl-cyanoacrylate + Metacryloxysulfolane could be a valid tool to reduce the necessary number of sutures and to reduce the time required for graft fixation graft fixation with consistent results in long-term follow-up.
Goal Setting Among Experienced and Novice Occupational Therapists in a Rehabilitation Center
Authors: Šuc Lea , Švajger Andreja , Bratun Urša 
Published: July 2020

Background. Collaborative goal setting is an important part of client-centered occupational therapy. However, not all therapists have comparable skills when it comes to setting goals. Purpose. The aim of our study was to explore the experiences of novice and expert occupational therapists who use the Canadian Occupational Performance Measure in the process of goal setting. Method. This study followed a focused ethnography approach. Four beginners and four experienced occupational therapists were interviewed about their experiences with goal setting. We also observed them during a goal setting session. Data were analyzed using thematic analysis. Findings. The four main themes that emerged from the analysis showed both similarities and differences between novice and experienced therapists, especially in the areas of communication, guidance, and flexibility, as well as dilemmas they were facing. Implications. Our findings challenge the client-centeredness of the participants and the relevance of work experience when it comes to collaborative goal setting.
Exploring concomitant neuroimaging and genetic alterations in patients with and patients without auditory verbal hallucinations: A pilot study and mini review
Authors: Yu Haiping , Ying Wang , Li Gang , Lin Xiaodong , Jiang Deguo , Chen Guangdong , Chen Suling , Sun Xiuhai , Xu Yong , Ye Jiaen , Zhuo Chuanjun 
Published: July 2020

Objective To explore concomitant neuroimaging and genetic alterations in patients with schizophrenia with or without auditory verbal hallucinations (AVHs), and to discuss the use of pattern recognition techniques in the development of an objective index that may improve diagnostic accuracy and treatment outcomes for schizophrenia. Methods The pilot study included patients with schizophrenia with AVHs (SCH-AVH group) and without AVHs (SCH-no AVH group). High throughput sequencing (HTS) was performed to explore RNA networks. Global functional connectivity density (gFCD) analysis was performed to assess functional connectivity (FC) alterations of the default mode network (DMN). Quantitative long noncoding (lnc) RNA and mRNA expression data were related to peak T values of gFCDs using Pearson’s correlation coefficient analysis. Results Compared with the SCH-no AVH group ( n = 5), patients in the SCH-AVH group ( n = 5) exhibited differences in RNA expression in RNA networks that were related to AVH severity, and displayed alterations in FC (reflected by gFCD differences) within the DMN (posterior cingulate and dorsal-medial prefrontal cortex), and in the right parietal lobe, left occipital lobe, and left temporal lobe. Peak lncRNA expression values were significantly related to peak gFCD T values within the DMN. Conclusion Among patients with schizophrenia, there are concomitant FC and genetic expression alterations associated with AVHs. Data from pattern recognition studies may inform the development of an objective index aimed at improving early diagnostic accuracy and treatment planning for patients with schizophrenia with and without AVHs.
Evaluation of the disability assessment Longshi scale: A multicenter study
Authors: Wang Yao , Li Shanshan , Pan Weiyi , Xiao Peng , Zhang Jiehong , Wang Qing-Mei , Luo Xun , Wang Yulong 
Published: July 2020

Objective We investigated factors affecting the disability assessment Longshi scale, and differences between the Longshi and Barthel scales, as well as modified Rankin scale (mRS), to determine whether the Longshi scale is superior to the other scales. Methods This cross-sectional study included 721 participants with disability. We performed the t-test, analysis of variance, Pearson’s correlation test, and multiple linear regression to analyze group differences and define explanatory variables. Results The Longshi scale had a strong positive correlation with the Barthel scale (r = 0.868) but a weak negative correlation with the mRS (r = –0.185). Scores obtained among seven study hospitals in two provinces of southeast China were significantly different (F = 8.034). Social activities of participants with disability can be positively predicted using the Longshi (β = 0.251) and Barthel scales (β = 0.276). However, age has a weak negative correlation with the Longshi scale (r = –0.163). Conclusion Training did not cause significant variations in assessment using the Longshi scale. However, the results differed among different regions. The Longshi scale showed a strong correlation with the Barthel scale but a weak correlation with the mRS. Assessment time was shorter using the Longshi scale and the scale can be used to predict the social activities of individuals with disability.