bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD1 blockade enhances K+channel activity, Ca2+signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer
Authors: Newton Hannah S , Gawali Vaibhavkumar S , Chimote Ameet A , Lehn Maria A , Palackdharry Sarah M , Hinrichs Benjamin H , Jandarov Roman , Hildeman David , Janssen Edith M , Wise-Draper Trisha M , Conforti Laura 
Published: October 2020

BackgroundImmunotherapy has emerged as a promising treatment modality for head and neck squamous cell carcinoma (HNSCC). Pembrolizumab, an anti-programmed death 1 antibody, is an immunotherapy agent currently approved for metastatic HNSCC and curative intent clinical trials. Although clinical responses to pembrolizumab are promising, many patients fail to respond. However, it is well known that T cell cytotoxicity and chemotaxis are critically important in the elimination of HNSCC tumors. These functions depend on ion channel activity and downstream Ca2+fluxing abilities, which are defective in patients with HNSCC. The purpose of this study was to elucidate the effects of pembrolizumab on potassium (K+) channel (KCa3.1 and Kv1.3) activity, Ca2+fluxes, and chemotaxis in the cytotoxic T cells of patients with HNSCC and to determine their correlation with treatment response.MethodsFunctional studies were conducted in CD8+peripheral blood T cells (PBTs) and tumor infiltrating lymphocytes (TILs) from patients with HNSCC treated with pembrolizumab. Untreated patients with HNSCC were used as controls. The ion channel activity of CD8+T cells was measured by patch-clamp electrophysiology; single-cell Ca2+fluxing abilities were measured by live microscopy. Chemotaxis experiments were conducted in a three-dimensional collagen matrix. Pembrolizumab patients were stratified as responders or non-responders based on pathological response (percent of viable tumor remaining at resection; responders: ≤80% viable tumor; non-responders: >80% viable tumor).ResultsPembrolizumab increased K+channel activity and Ca2+fluxes in TILs independently of treatment response. However, in PBTs from responder patients there was an increased KCa3.1 activity immediately after pembrolizumab treatment that was accompanied by a characteristic increase in Kv1.3 and Ca2+fluxes as compared with PBTs from non-responder patients. The effects on Kv1.3 and Ca2+were prolonged and persisted after tumor resection. Chemotaxis was also improved in responder patients’ PBTs. Unlike non-responders’ PBTs, pembrolizumab increased their ability to chemotax in a tumor-like, adenosine-rich microenvironment immediately after treatment, and additionally they maintained an efficient chemotaxis after tumor resection.ConclusionsPembrolizumab enhanced K+channel activity, Ca2+fluxes and chemotaxis of CD8+T cells in patients with HNSCC, with a unique pattern of response in responder patients that is conducive to the heightened functionality of their cytotoxic T cells.
HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial
Authors: Song Yan , Li Ning , Li Qun , Liang Xinjun , Zhang Shu , Fan Qingxia , Yin Xianli , Zhuang Zhixiang , Liu Yunpeng , Zhang Jingdong , Kou Xiaoge , Zhong Haijun , Wang Xiaofei , Dou Yiwei , Huang Jing 
Published: October 2020

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246
Post-traumatic growth and influencing factors among frontline nurses fighting against COVID-19
Authors: Cui Pan pan , Wang Pan pan , Wang Kun , Ping Zhiguang , Wang Peng , Chen Changying 
Published: October 2020

ObjectiveTo explore the level and influencing factors of frontline nurses’ post-traumatic growth (PTG) during COVID-19 epidemic.MethodsA cross-sectional survey was conducted in February 2020 in three hospitals in China. The Post-traumatic Growth Inventory (PTGI) was used to investigate the PTG of frontline nurses. Data on related factors, including demographic characteristics and subjective variables, were collected. The Event-Related Rumination Inventory was used to assess rumination. Pearson’s or Spearman’s correlation was calculated for bivariate analysis. Independent sample t-tests or one-way analysis of variance and multiple linear regression analysis were used to examine the related factors.ResultsA total of 179 frontline nurses were recruited, and 167 were included in the analyses. The mean PTG score was 70.53±17.26. The bivariate analyses showed that deliberate rumination was modestly positively correlated with PTG (r=0.557, p<0.01), while intrusive rumination had a modest negative correlation with PTG (r=−0.413, p<0.01). Multiple linear regression demonstrated that working years, self-confidence in frontline work, awareness of risk, psychological intervention or training during the epidemic and deliberate rumination were the main influencing factors of PTG among frontline nurses and accounted for 42.5% of the variance (F=31.626, p<0.001).ConclusionsThe PTG of frontline nurses was at a medium to high level and was influenced by working years, self-confidence in frontline work, awareness of risk, psychological intervention or training and deliberate rumination. It is necessary to strengthen psychological guidance and training for frontline nurses and promote their deliberate rumination on epidemic events to improve their PTG.
Patient perspectives of nuisance bleeding and adherence to dual antiplatelet therapy: a qualitative study
Authors: Pithara Christalla , Pufulete Maria , Johnson Thomas W. , Redwood Sabi 
Published: October 2020

ObjectiveTo understand the experiences of patients with dual antiplatelet therapy (DAPT) and nuisance bleeding, and their perspectives of the impact of nuisance bleeding on medication adherence and information seeking.MethodsWe conducted focus groups with patients who had undergone percutaneous coronary intervention, coronary artery bypass graft and conservatively managed acute coronary syndrome patients. Two focus groups were with patients at the early stages of treatment (0–3 months), and two with patients coming to the end of treatment (9–12 months). Group discussions were audio recorded, and recordings were transcribed verbatim, anonymised and analysed using framework analysis.FindingsNine patients taking DAPT for up to 3 months, and 12 taking DAPT between 9 and 12 months participated in the focus groups. We found that: (1) participants adhered to treatment when they believed DAPT was important to health outcomes; (2) those who experienced nuisance bleeding reported symptoms to be mild and manageable; (3) participants’ and their family’s understanding of DAPT risks and benefits, and their ability to manage symptoms, influenced perspectives of and experiences with adherence. Factors influencing DAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from hospital.ConclusionsPositive attitudes towards adherence were facilitated by knowledge and understanding of DAPT and confidence in dealing with symptoms caused by DAPT, but hindered by lack of opportunities to access relevant, timely and appropriate medication counselling. Education interventions should aim to support medication literacy through family-centred approaches and involve patients and families at all stages of intervention design and evaluation.
Canadian 24-Hour Movement Guidelines for Adults aged 18–64 years and Adults aged 65 years or older: an integration of physical activity, sedentary behaviour, and sleep
Authors: Ross Robert , Chaput Jean-Philippe , Giangregorio Lora M. , Janssen Ian , Saunders Travis J. , Kho Michelle E. , Poitras Veronica J. , Tomasone Jennifer R. , El-Kotob Rasha , McLaughlin Emily C. , Duggan Mary , Carrier Julie , Carson Valerie , Chastin Sebastien F. , Latimer-Cheung Amy E. , Chulak-Bozzer Tala , Faulkner Guy , Flood Stephanie M. , Gazendam Mary Kate , Healy Genevieve N. , Katzmarzyk Peter T. , Kennedy William , Lane Kirstin N. , Lorbergs Amanda , Maclaren Kaleigh , Marr Sharon , Powell Kenneth E. , Rhodes Ryan E. , Ross-White Amanda , Welsh Frank , Willumsen Juana , Tremblay Mark S. 
Published: October 2020

The Canadian Society for Exercise Physiology assembled a Consensus Panel representing national organizations, content experts, methodologists, stakeholders, and end-users and followed an established guideline development procedure to create the Canadian 24-Hour Movement Guidelines for Adults aged 18–64 years and Adults aged 65 years or older: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These guidelines underscore the importance of movement behaviours across the whole 24-h day. The development process followed the strategy outlined in the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. A large body of evidence was used to inform the guidelines including 2 de novo systematic reviews and 4 overviews of reviews examining the relationships among movement behaviours (physical activity, sedentary behaviour, sleep, and all behaviours together) and several health outcomes. Draft guideline recommendations were discussed at a 4-day in-person Consensus Panel meeting. Feedback from stakeholders was obtained by survey (n = 877) and the draft guidelines were revised accordingly. The final guidelines provide evidence-based recommendations for a healthy day (24-h), comprising a combination of sleep, sedentary behaviours, and light-intensity and moderate-to-vigorous-intensity physical activity. Dissemination and implementation efforts with corresponding evaluation plans are in place to help ensure that guideline awareness and use are optimized.Novelty First ever 24-Hour Movement Guidelines for Adults aged 18–64 years and Adults aged 65 years or older with consideration of a balanced approach to physical activity, sedentary behaviour, and sleep Finalizes the suite of 24-Hour Movement Guidelines for Canadians across the lifespan
On higher dimensional self-similar axion–dilaton solutions
Authors: Hatefi Ehsan , Vanzan Eleonora 
Published: October 2020

AbstractWe show that solutions of the self-similar gravitational collapse in the Einstein-axion–dilaton system exist in higher-dimensional spacetimes. These solutions are invariant under spacetime dilation combined with internal SL(2,$$\mathbb {R}$$
R
) transformations. We rely on the recent setup of Antonelli and Hatefi (JHEP 03:074, arXiv:1912.00078 [hep-th], 2020) and use it for the three different conjugacy classes (elliptic, parabolic and hyperbolic) in higher dimensions. Lastly, we identify new families of physically distinguishable self-similar solutions for all three conjugacy classes in six and seven dimensions.
Investigation of the electrical conduction mechanisms in P-type amorphous germanium electrical contacts for germanium detectors in searching for rare-event physics
Authors: Bhattarai S. , Panth R. , Wei W.-Z. , Mei H. , Mei D.-M. , Raut M.-S. , Acharya P. , Wang G.-J. 
Published: October 2020

AbstractFor the first time, electrical conduction mechanisms in the disordered material system is experimentally studied for p-type amorphous germanium (a-Ge) used for high-purity Ge detector contacts. The localization length and the hopping parameters in a-Ge are determined using the surface leakage current measured from three high-purity planar Ge detectors. The temperature dependent hopping distance and hopping energy are obtained for a-Ge fabricated as the electrical contact materials for high-purity Ge planar detectors. As a result, we find that the hopping energy in a-Ge increases as temperature increases while the hopping distance in a-Ge decreases as temperature increases. The localization length of a-Ge is on the order of$$2.13^{-0.05}_{+0.07}\mathrm{{A}}^\circ $$2.13+0.07-0.05A∘to$$5.07^{-0.83}_{+2.58}\mathrm{{A}}^\circ $$5.07+2.58-0.83A∘, depending on the density of states near the Fermi energy level within bandgap. Using these parameters, we predict that the surface leakage current from a Ge detector with a-Ge contacts can be much smaller than one yocto amp (yA) at helium temperature, suitable for rare-event physics searches.
The Potential of Circular RNAs as Cancer Biomarkers
Authors: Brown Jason R. , Chinnaiyan Arul M. 
Published: October 2020

AbstractCircular RNA (circRNA) is a covalently closed RNA structure that has several proposed functions related to cancer development. Recently, cancer-specific and tissue-specific circRNAs have been identified by high-throughput sequencing and are curated in publicly available databases. CircRNAs have features that are ideal properties of biomarkers, including conservation, abundance, and stability in plasma, saliva, and urine. Many circRNAs with predictive and prognostic significance in cancer have been described, and functional mechanisms for some circRNAs have been suggested. CircRNA also has great potential as a noninvasive biomarker for early cancer detection, although further investigation is necessary before clinical application is feasible.See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”
Fibroblast Nox2 (NADPH Oxidase-2) Regulates ANG II (Angiotensin II)–Induced Vascular Remodeling and Hypertension via Paracrine Signaling to Vascular Smooth Muscle Cells
Authors: Harrison Craig B. , Trevelin Silvia Cellone , Richards Daniel A. , Santos Celio X.C. , Sawyer Greta , Markovinovic Andrea , Zhang Xiaohong , Zhang Min , Brewer Alison C. , Yin Xiaoke , Mayr Manuel , Shah Ajay M. 
Published: October 2020

Objective:
The superoxide-generating Nox2 (NADPH oxidase-2) is expressed in multiple cell types. Previous studies demonstrated distinct roles for cardiomyocyte, endothelial cell, and leukocyte cell Nox2 in ANG II (angiotensin II)–induced cardiovascular remodeling. However, the in vivo role of fibroblast Nox2 remains unclear.

Approach and Results:
We developed a novel mouse model with inducible fibroblast-specific deficiency of Nox2 (fibroblast-specific Nox2 knockout or Fibro-Nox2KO mice) and investigated the responses to chronic ANG II stimulation. Fibro-Nox2KO mice showed no differences in basal blood pressure or vessel wall morphology, but the hypertensive response to ANG II infusion (1.1 mg/[kg·day] for 14 days) was substantially reduced as compared to control Nox2-Flox littermates. This was accompanied by a significant attenuation of aortic and resistance vessel remodeling. The conditioned medium of ANG II–stimulated primary fibroblasts induced a significant increase in vascular smooth muscle cell growth, which was inhibited by the short hairpin RNA (shRNA)-mediated knockdown of fibroblast Nox2. Mass spectrometric analysis of the secretome of ANG II–treated primary fibroblasts identified GDF6 (growth differentiation factor 6) as a potential growth factor that may be involved in these effects. Recombinant GDF6 induced a concentration-dependent increase in vascular smooth muscle cell growth while chronic ANG II infusion in vivo significantly increased aortic GDF6 protein levels in control mice but not Fibro-Nox2KO animals. Finally, silencing GDF6 in fibroblasts prevented the induction of vascular smooth muscle cell growth by fibroblast-conditioned media in vitro.

Conclusions:
These results indicate that fibroblast Nox2 plays a crucial role in the development of ANG II–induced vascular remodeling and hypertension in vivo. Mechanistically, fibroblast Nox2 may regulate paracrine signaling to medial vascular smooth muscle cells via factors, such as GDF6.
Trends in Short‐ and Long‐Term ST‐Segment–Elevation Myocardial Infarction Prognosis Over 3 Decades: A Mediterranean Population‐Based ST‐Segment–Elevation Myocardial Infarction Registry
Authors: García‐García Cosme , Oliveras Teresa , Serra Jordi , Vila Joan , Rueda Ferran , Cediel German , Labata Carlos , Ferrer Marc , Carrillo Xavier , Dégano Irene R. , De Diego Oriol , El Ouaddi Nabil , Montero Santiago , Mauri Josepa , Elosua Roberto , Lupón Josep , Bayes‐Genis Antoni , Martínez‐Membrive Maria José , Zamora Elisabeth , Caballero Angel , Llibre Cinta , Rodríguez‐Leor Oriol , Fernandez‐Nofrerias Eduard , Abdul‐Jawad Omar , Vilalta Victoria 
Published: October 2020

Background
Coronary artery disease remains a major cause of death despite better outcomes of ST‐segment–elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti‐STEMI registry of in‐hospital, 28‐day, and 1‐year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis.

Methods and Results

Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28‐day and 1‐year STEMI mortality and in‐hospital complication trends across these periods. Mean patient age was 61.6±12.6 years, and 79.3% were men. The 28‐day all‐cause mortality declined from period 1 to period 5 (10.4% versus 6.0%;
P
<0.001), with a 40% reduction after multivariable adjustment (hazard ratio [HR], 0.6; 95% CI, 0.46–0.80;
P
<0.001). One‐year all‐cause mortality declined from period 1 to period 5 (11.7% versus 9.0%;
P
=0.001), with a 24% reduction after multivariable adjustment (HR, 0.76; 95% CI, 0.60–0.98;
P
=0.036). A significant temporal reduction was observed for in‐hospital complications including postinfarct angina (−78%), ventricular tachycardia (−57%), right ventricular dysfunction (−48%), atrioventricular block (−45%), pericarditis (−63%), and free wall rupture (−53%). Primary ventricular fibrillation showed no significant downslope trend.

Conclusions
In‐hospital STEMI complications and 28‐day and 1‐year mortality rates have dropped markedly in the past 30 years. Reducing ischemia‐driven primary ventricular fibrillation remains a major challenge.
Augmenting Frontal Dopamine Tone Enhances Maintenance over Gating Processes in Working Memory
Authors: Furman Daniella J. , Zhang Zhihao , Chatham Christopher H. , Good Maxwell , Badre David , Hsu Ming , Kayser Andrew S. 
Published: October 2020

Abstract
The contents of working memory must be maintained in the face of distraction, but updated when appropriate. To manage these competing demands of stability and flexibility, maintained representations in working memory are complemented by distinct gating mechanisms that selectively transmit information into and out of memory stores. The operations of such dopamine-dependent gating systems in the midbrain and striatum and their complementary dopamine-dependent memory maintenance operations in the cortex may therefore be dissociable. If true, selective increases in cortical dopamine tone should preferentially enhance maintenance over gating mechanisms. To test this hypothesis, tolcapone, a catechol-O-methyltransferase inhibitor that preferentially increases cortical dopamine tone, was administered in a randomized, double-blind, placebo-controlled, within-subject fashion to 49 participants who completed a hierarchical working memory task that varied maintenance and gating demands. Tolcapone improved performance in a condition with higher maintenance requirements and reduced gating demands, reflected in a reduction in the slope of RTs across the distribution. Resting-state fMRI data demonstrated that the degree to which tolcapone improved performance in individual participants correlated with increased connectivity between a region important for stimulus response mappings (left dorsal premotor cortex) and cortical areas implicated in visual working memory, including the intraparietal sulcus and fusiform gyrus. Together, these results provide evidence that augmenting cortical dopamine tone preferentially improves working memory maintenance.
Compassion Fatigue and Resiliency Factors in Animal Shelter Workers
Authors: Levitt Alexis L. , Gezinski Lindsay B. 
Published: October 2020

Abstract
This phenomenological study explored compassion fatigue and resiliency factors in animal shelter workers. Compassion fatigue is a phenomenon in which individuals become traumatized through the process of helping others. The sample included seven current and former animal shelter workers. The researchers conducted semi-structured interviews to examine general experiences with animal shelter work as well as compassion fatigue. The researchers read the transcripts multiple times and coded the data into themes and sub-themes. Four major themes and five sub-themes emerged from the data. These themes were 1) Intrinsic Motivations including (a) Right reason, (b) Affinity with animals and (c) Attachment to animals; 2) Purpose, including (a) Making a difference and (b) Focusing on the positive; 3) Social supports; and 4) Coping Strategies. The study has important practical implications, including the potential benefits of screening job applicants for intrinsic motivations and fostering positive relationships between coworkers and the animals they work with.