bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shorter Treatment-Naïve Leukocyte Telomere Length is Associated with Poorer Overall Survival of Patients with Pancreatic Ductal Adenocarcinoma
Authors: Antwi Samuel O. , Bamlet William R. , Cawthon Richard M. , Rabe Kari G. , Druliner Brooke R. , Sicotte Hugues , Jatoi Aminah , Mahipal Amit , Boardman Lisa A. , Oberg Ann L. , Petersen Gloria M. 
Published: November 2020

Abstract

Background:
Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

Methods:
The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.

Results:
Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HRcontinuous = 1.13, 95% CI: 1.01–1.28, P = 0.03; HRshortest vs. longest LTL = 1.29, 95% CI: 1.05–1.59, Ptrend = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HRcontinuous = 0.91; 95% CI: 0.73–1.12), locally advanced tumors (HRcontinuous = 1.29; 95% CI: 1.07–1.56), and metastatic tumors (HRcontinuous = 1.17; 95% CI: 0.96–1.42), Pinteraction = 0.04.

Conclusion:
Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.

Impact:
Peripheral blood LTL might be a prognostic marker for PDAC.
Neoadjuvant Therapy for Melanoma: A U.S. Food and Drug Administration—Melanoma Research Alliance Public Workshop
Authors: Mueller Kristen L. , Theoret Marc R. , Lemery Steven J. , Amiri-Kordestani Laleh , Ariyan Charlotte E. , Atkins Michael B. , Berry Donald A. , Blank Christian U. , DeMichele Angela M. , Forde Patrick M. , Ibrahim Nageatte , Keegan Patricia , Mitchell Tara C. , Moss Rebecca A. , Robert Caroline , Sridhara Rajeshwari , Taube Janis M. , Tetzlaff Michael T. , Wargo Jennifer A. , Flaherty Keith T. , Kaplan Michael J. , Topalian Suzanne L. , Ward Ashley F. , Hurlbert Marc S. 
Published: November 2020

Abstract
Tremendous progress has been made in treating patients with metastatic melanoma over the past decade. In that timeframe, the FDA has approved 12 novel treatments for patients with advanced unresectable melanoma, comprising both kinase-targeted therapies and immune checkpoint inhibitors (ICI), and five treatments for adjuvant (postoperative) use in patients with high-risk resectable stage III melanoma. It is not known whether outcomes can be further improved by administering kinase inhibitors or ICI in the neoadjuvant (presurgical) setting in patients with high-risk resectable melanomas. Noting research community interest in exploring the neoadjuvant approach for treating melanoma and recognizing that early harmonization of methodologies may expedite the development of therapeutics in this space, the FDA and Melanoma Research Alliance convened a public workshop on November 6, 2019, in National Harbor, Maryland, to discuss key issues. The workshop consisted of 23 faculty and included more than 250 live participants. Topics discussed included opportunities for advancing novel endpoints for regulatory purposes as well as translational research, clinical trial design considerations, and strategies for optimizing patient selection while mitigating risk.
FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase–zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer
Authors: Gao Jennifer J. , Osgood Christy L. , Gong Yutao , Zhang Hui , Bloomquist Erik W. , Jiang Xiling , Qiu Junshan , Yu Jingyu , Song Pengfei , Rahman Nam Atiqur , Chiu Haw-Jyh , Ricks Tiffany K. , Rizvi Fatima , Hou Sherry , Wilson Willie , Abukhdeir Abde M. , Seidman Jeffrey , Ghosh Soma , Philip Reena , Pierce William F. , Bhatnagar Vishal , Kluetz Paul G. , Pazdur Richard , Beaver Julia A. , Amiri-Kordestani Laleh 
Published: November 2020

Abstract
On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early-stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multicenter comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared with intravenous pertuzumab and intravenous trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of intravenous pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of intravenous trastuzumab. The primary endpoints were met with the observed lower limit of the two-sided 90% confidence intervals above the prespecified noninferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to intravenous, allowing for extrapolation and approval of all breast cancer indications for which intravenous trastuzumab and pertuzumab are approved.
Artificial Intelligence–Electrocardiography to Predict Incident Atrial Fibrillation
Authors: Christopoulos Georgios , Graff-Radford Jonathan , Lopez Camden L. , Yao Xiaoxi , Attia Zachi I. , Rabinstein Alejandro A. , Petersen Ronald C. , Knopman David S. , Mielke Michelle M. , Kremers Walter , Vemuri Prashanthi , Siontis Konstantinos C. , Friedman Paul A. , Noseworthy Peter A. 
Published: November 2020

Background:
An artificial intelligence (AI) algorithm applied to electrocardiography during sinus rhythm has recently been shown to detect concurrent episodic atrial fibrillation (AF). We sought to characterize the value of AI–enabled electrocardiography (AI-ECG) as a predictor of future AF and assess its performance compared with the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology–AF) in a population-based sample.

Methods:
We calculated the probability of AF using AI-ECG, among participants in the population-based Mayo Clinic Study of Aging who had no history of AF at the time of the baseline study visit. Cox proportional hazards models were fit to assess the independent prognostic value and interaction between AI-ECG AF model output and CHARGE-AF score. C statistics were calculated for AI-ECG AF model output, CHARGE-AF score, and combined AI-ECG and CHARGE-AF score.

Results:

A total of 1936 participants with median age 75.8 (interquartile range, 70.4–81.8) years and median CHARGE-AF score 14.0 (IQR, 13.2–14.7) were included in the analysis. Participants with AI-ECG AF model output of >0.5 at the baseline visit had cumulative incidence of AF 21.5% at 2 years and 52.2% at 10 years. When included in the same model, both AI-ECG AF model output (hazard ratio, 1.76 per SD after logit transformation [95% CI, 1.51–2.04]) and CHARGE-AF score (hazard ratio, 1.90 per SD [95% CI, 1.58–2.28]) independently predicted future AF without significant interaction (
P
=0.54). C statistics were 0.69 (95% CI, 0.66–0.72) for AI-ECG AF model output, 0.69 (95% CI, 0.66–0.71) for CHARGE-AF, and 0.72 (95% CI, 0.69–0.75) for combined AI-ECG and CHARGE-AF score.

Conclusions:
In the present study, both the AI-ECG AF model output and CHARGE-AF score independently predicted incident AF. The AI-ECG may offer a means to assess risk with a single test and without requiring manual or automated clinical data abstraction.
Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release
Authors: Simon Jillian N. , Vrellaku Besarte , Monterisi Stefania , Chu Sandy M. , Rawlings Nadiia , Lomas Oliver , Marchal Gerard A. , Waithe Dominic , Syeda Fahima , Gajendragadkar Parag R. , Jayaram Raja , Sayeed Rana , Channon Keith M. , Fabritz Larissa , Swietach Pawel , Zaccolo Manuela , Eaton Philip , Casadei Barbara 
Published: November 2020

Background:
Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, PKARIα (type-1 protein kinase A) can be reversibly oxidized, forming interprotein disulfide bonds in the holoenzyme complex. However, the effect of PKARIα disulfide formation on downstream signaling in the heart, particularly under states of oxidative stress such as ischemia and reperfusion (I/R), remains unexplored.

Methods:

Atrial tissue obtained from patients before and after cardiopulmonary bypass and reperfusion and left ventricular (LV) tissue from mice subjected to I/R or sham surgery were used to assess PKARIα disulfide formation by immunoblot. To determine the effect of disulfide formation on PKARIα catalytic activity and subcellular localization, live-cell fluorescence imaging and stimulated emission depletion super-resolution microscopy were performed in
prkar1
knock-out mouse embryonic fibroblasts, neonatal myocytes, or adult LV myocytes isolated from “redox dead” (Cys17Ser) PKARIα knock-in mice and their wild-type littermates. Comparison of intracellular calcium dynamics between genotypes was assessed in fura2-loaded LV myocytes, whereas I/R-injury was assessed ex vivo.

Results:

In both humans and mice, myocardial PKARIα disulfide formation was found to be significantly increased (2-fold in humans,
P
=0.023; 2.4-fold in mice,
P
<0.001) in response to I/R in vivo. In mouse LV cardiomyocytes, disulfide-containing PKARIα was not found to impact catalytic activity, but instead led to enhanced AKAP (A-kinase anchoring protein) binding with preferential localization of the holoenzyme to the lysosome. Redox-dependent regulation of lysosomal two-pore channels by PKARIα was sufficient to prevent global calcium release from the sarcoplasmic reticulum in LV myocytes, without affecting intrinsic ryanodine receptor leak or phosphorylation. Absence of I/R-induced PKARIα disulfide formation in “redox dead” knock-in mouse hearts resulted in larger infarcts (2-fold,
P
<0.001) and a concomitant reduction in LV contractile recovery (1.6-fold,
P
<0.001), which was prevented by administering the lysosomal two-pore channel inhibitor Ned-19 at the time of reperfusion.

Conclusions:
Disulfide modification targets PKARIα to the lysosome, where it acts as a gatekeeper for two-pore channel–mediated triggering of global calcium release. In the postischemic heart, this regulatory mechanism is critical for protection from extensive injury and offers a novel target for the design of cardioprotective therapeutics.
The Problem of the Absent I
Authors: D’Alessio Giovan Battista 
Published: November 2020

Abstract
One of the greatest paradoxes of ancient Greek lyric poetry is its fundamental tension between the vivid evocation of a performance communicative context and the capability of the text to transcend the context itself. A key aspect of this is the way in which language can exploit both poles of this tension: the presentness of the performance and the transcendence of the text. This is a source of crucial interpretative problems, as well as of complex expressive potentialities. The focus of this paper is to examine some of the ways in which the shift of the use of first person indexicals serves the dialogue between text and performance, proceeding through three stages. In the first place I briefly analyze some different genres of discourse (drama, epistle, lyric) that in Archaic and Classical Greek display a complex use of indexicality calling attention to the ‘mediated’ nature of the communication process (§ 2). In the second stage I revise some examples of ‘mediated’ indexicality in Greek lyric in general (§ 3) and in Pindaric poetry in particular (§ 4). In the third stage I locate these cases within a wider comparative approach, exploring a suitable theoretical explanation of this important feature (§ 5).
Southern Ocean Heat Storage, Reemergence, and Winter Sea Ice Decline Induced by Summertime Winds
Authors: Doddridge Edward W. , Marshall John , Song Hajoon , Campin Jean-Michel , Kelley Maxwell 
Published: November 2020

AbstractThe observational record shows a substantial 40-yr upward trend in summertime westerly winds over the Southern Ocean, as characterized by the southern annular mode (SAM) index. Enhanced summertime westerly winds have been linked to cold summertime sea surface temperature (SST) anomalies. Previous studies have suggested that Ekman transport or upwelling is responsible for this seasonal cooling. Here, another process is presented in which enhanced vertical mixing, driven by summertime wind anomalies, moves heat downward, cooling the sea surface and simultaneously warming the subsurface waters. The anomalously cold SSTs draw heat from the atmosphere into the ocean, leading to increased depth-integrated ocean heat content. The subsurface heat is returned to the surface mixed layer during the autumn and winter as the mixed layer deepens, leading to anomalously warm SSTs and potentially reducing sea ice cover. Observational analyses and numerical experiments support our proposed mechanism, showing that enhanced vertical mixing produces subsurface warming and cools the surface mixed layer. Nevertheless, the dominant driver of surface cooling remains uncertain; the relative importance of advective and mixing contributions to the surface cooling is model dependent. Modeling results suggest that sea ice volume is more sensitive to summertime winds than sea ice extent, implying that enhanced summertime westerly winds may lead to thinner sea ice in the following winter, if not lesser ice extent. Thus, strong summertime winds could precondition the sea ice cover for a rapid retreat in the following melt season.
Detectable Intensification of Hourly and Daily Scale Precipitation Extremes across Eastern China
Authors: Chen Yang , Li Wei , Jiang Xiaoling , Zhai Panmao , Luo Yali 
Published: November 2020

AbstractDetecting long-term changes in precipitation extremes over monsoon regions remains challenging due to large observational uncertainty, high internal variability at the regional scale, and climate models’ deficiency in simulating monsoon physics. This is particularly true for Eastern China, as illustrated by limited yet controversial detection results for daily scale precipitation extremes and the lack of detection analysis on hourly scale extremes there. Relying on high-quality gauge observations, two complementary techniques are used to detect the footprint of anthropogenic forcings in observed changes in both hourly and daily scale precipitation extremes across Eastern China. Results show that, scaled with global-mean surface temperature during 1970–2017, the regional-scale intensification nearly doubles the Clausius–Clapeyron rate (C-C; ~6.5% °C−1) for the wettest 10 h in the period and almost triples the C-C rate for the top 10 heaviest daily precipitation extremes. The intensification at both time scales, as well as the resulting increase in frequency, is discernibly stronger and more widespread than expected due to random internal variability. This not only lends supports to the model-based detection of forced trends for daily scale precipitation extremes, but it also suggests that anthropogenic warming has already be intensifying hourly scale precipitation extremes in this monsoon region. The magnitude and detectability of observed changes arise primarily from systematic intensification of non-tropical-cyclone-related precipitation extremes in response to the past warming.
Women health: Psychological and most prominent somatic problems in 3-year follow-up in Bosnian refugees
Authors: Sarajlić Vuković Iris , Jovanović Nikolina , Džubur Kulenović Alma , Britvić Dolores , Mollica Richard F. 
Published: November 2020

Background: Little is known about gender differences among people exposed to war related trauma. Aim of this study is to explore gender differences in health status and comorbidity of mental and physical disorders in a cohort of Bosnian refugees followed up for 3 years (1996–1999). Methods: This longitudinal study included 534 subjects followed up for 3 years. The interviews were conducted in refugee camps in Varaždin, Croatia in Bosnian language. Data were collected using Harvard Trauma Questionnaire (Bosnian version) and Hopkins Checklist-25, respectively. Physical health disorders were self-reported. Results: In both assessments there was a statistically significant difference between men and women in the number of physical health disorders, even when results were controlled for educational status. Although there was no difference in total number of symptoms in both assessments ( F = 0.32; df = 1; p > 0.05 and F = 1.15; df = 1; p > 0.05), important physical health disorders were significantly more frequent among women than in men in different educational groups, namely high blood pressure and cardiovascular diseases, arthritis, and anaemia. Asthma, tuberculosis, cirrhosis of the liver, ulcer and epilepsy were more frequent in men than in women. There were no differences in frequencies of psychiatric disorders at baseline, but frequency of psychiatric disorders in women was higher at endpoint for uneducated respondents. There was significant difference compared to men in group of respondents without formal education, but only in comorbidity of PTSD and depression which was more often present in females (22.1%) than in males (3.6%). Conclusion: Our findings indicate the importance of gender and education on mental and physical health of people exposed to warrelated trauma. Long term health monitoring and programs, especially related to women’s health are needed in order to avoid lasting consequences.
Psychological response of children to home confinement during COVID-19: A qualitative arts-based research
Authors: Abdulah Deldar Morad , Abdulla Bayar Mohammed Omar , Liamputtong Pranee 
Published: November 2020

Background: The evidence has shown that children are more susceptible to the emotional effects of traumatic events such as outbreaks with the possible disruption in their daily lives. Aim: In this paper, we discussed the psychological wellbeing of children during the COVID-19 outbreak through the art-based qualitative study using the drawing method among children in Iraqi Kurdistan. Methods: In this qualitative arts-based research study, 15 children aged 6 to 13 years old who were confined at home during the COVID-19 outbreak for at least 1 month were included following obtaining the consent from their parents. The children were asked to draw his/her feelings, reflections, and responses during the COVID-19 on a paper. The children were guided to paint their reflections during the COVID-19 based on the following criteria: if they experienced loneliness, tiredness, insomnia, depression, worry or anxiety, or have behavior changes and their relationship with their parents and other siblings. Results: This study showed that children have a high level of stress at home during the COVID-19 outbreak. The children had great fear about the coronavirus. They experienced loneliness and stress, and felt sad, depressed due to home confinement and social distancing. The possibility of infection by coronavirus has occupied their entire mind. Mental health care providers must take the experiences of children who are caught in this global pandemic seriously and ensure that appropriate care is offered to the children and their parents. Conclusions: The children exhibited a strong feeling of distress, loneliness, and fear during the COVID-19 outbreak. This has implications for mental health care.
The Effects of the Chair the Fed Simulation on High School Students’ Knowledge
Authors: Duzhak Evgeniya , Hoff Jody , Lopus Jane S. 
Published: November 2020

Chair the Fed is an award-winning online simulation developed by the Federal Reserve Bank of San Francisco to teach about the role of the Fed in achieving its dual mandate goals of stable prices and maximum employment. It is widely used, with an average of close to 85,000 games started each month in 2019. This article describes Chair the Fed and the results of a controlled experiment to determine its effects on learning in high school economics classes in the Fed’s 12th district. We find that students who played Chair the Fed score significantly higher on a 10-question posttest compared with students who learned about the Fed and monetary policy in more traditional ways. In evaluating our results, we compare difference-in-difference regression modeling with the traditional economic education model where the posttest score is regressed on the pretest score, and find that our results are robust across both specifications. JEL Classifications: A20, A21, E52, E58
Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus
Authors: Abo-Shanab Assem M , Kholoussi Shams , Kandil Rania , Dorgham Dalia 
Published: November 2020

Background Juvenile onset systemic lupus erythematosus JO-SLE patients usually exhibit a more aggressive disease course compared to adult patients. Vitamin D deficiency is proposed to be associated with increased disease activity and flares of numerous autoimmune diseases like SLE, rheumatoid arthritis, and scleroderma. Objective To evaluate the level of IL-17, IFN-γ, and 25-OH Vit D in JO-SLE patients versus healthy controls, and determine the correlation of those inflammatory mediators with SLE disease activity and damage scores. Furthermore, to analyze the relationship between 25-OH Vit D levels with the inflammatory cytokines (IFN-γ and IL-17) in JO-SLE patients. Patients and methods Fifty JO-SLE patients and 25 controls were included in this study. Clinical and laboratory data of patients at the time of the study were recorded. SLE disease activity and damage were assessed using the SLEDAI-2K disease score and SLICC damage index, respectively. Plasma 25-OH Vit D, IFN-γ, and IL-17 concentrations were determined using the human ELISA kit. Results Plasma 25-OH Vit D levels (20 ng/mL) were significantly lower in JO-SLE patients compared to (31 ng/mL) controls (P = 0.014). Plasma levels of IFN-γ and IL-17 were significantly higher (163.5 and 25.5 pg./mL) in JO-SLE patients than (68.3 and 3 pg./mL) that of controls (P = 0.016 and P = 0.013). There was a significant negative correlation between 25-OH Vit D levels and SLEDAI-2K (R= -0.431) as well as IFN-γ (R= -0.471) plasma level (P = 0.022 and P = 0.027). Conclusion IFN-γ and IL-17 were significantly higher in JO-SLE patients, while 25-OH Vit D was significantly lower compared to controls. There was a negative correlation between 25-OH Vit D and each of SLEDAI-2K and IFN-γ.