bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fenretinide via NOXA Induction, Enhanced Activity of the BCL-2 Inhibitor Venetoclax in High BCL-2–Expressing Neuroblastoma Preclinical Models
Authors: Nguyen Thinh H. , Koneru Balakrishna , Wei Sung-Jen , Chen Wan Hsi , Makena Monish Ram , Urias Eduardo , Kang Min H. , Reynolds C. Patrick 
Published: September 2019

Abstract
Recurrent high-risk neuroblastoma is a childhood cancer that often fails to respond to therapy. Fenretinide (4-HPR) is a cytotoxic retinoid with clinical activity in recurrent neuroblastoma and venetoclax (ABT-199) is a selective inhibitor of the antiapoptotic protein B-cell lymphoma-2 (BCL-2). We evaluated activity of 4-HPR + ABT-199 in preclinical models of neuroblastoma. Patient-derived cell lines and xenografts from progressive neuroblastoma were tested. Cytotoxicity was evaluated by DIMSCAN, apoptosis by flow cytometry, and gene expression by RNA sequencing, quantitative RT-PCR, and immunoblotting. 4-HPR + ABT-199 was highly synergistic against high BCL-2–expressing neuroblastoma cell lines and significantly improved event-free survival of mice carrying high BCL-2–expressing patient-derived xenografts (PDX). In 10 matched-pair cell lines [established at diagnosis (DX) and progressive disease (PD) from the same patients], BCL-2 expression in the DX and PD lines was comparable, suggesting that BCL-2 expression at diagnosis may provide a biomarker for neuroblastomas likely to respond to 4-HPR + ABT-199. In a pair of DX (COG-N-603x) and PD (COG-N-623x) PDXs established from the same patient, COG-N-623x was less responsive to cyclophosphamide + topotecan than COG-N-603x, but both DX and PD PDXs were responsive to 4-HPR + ABT-199. Synergy of 4-HPR + ABT-199 was mediated by induction of NOXA via 4-HPR stimulation of reactive oxygen species that induced expression of ATF4 and ATF3, transcription factors for NOXA. Thus, fenretinide + venetoclax is a synergistic combination that warrants clinical testing in high BCL-2–expressing neuroblastoma.
Effect of HIF‐1α/miR‐10b‐5p/PTEN on Hypoxia‐Induced Cardiomyocyte Apoptosis
Authors: Wu Liping , Chen Yafen , Chen Yuanyuan , Yang Wenbo , Han Yanxin , Lu Lin , Yang Ke , Cao Jiumei 
Published: September 2019

Background

Few reports have addressed the mechanism by which microRNA miR‐10b‐5p regulates post–myocardial infarction (post‐
MI
) cardiomyocyte apoptosis under hypoxic conditions.

Methods and Results

C57
BL
/6 mice underwent surgical ligation of the left anterior descending artery to create an
MI
or ischemia/reperfusion animal model. The expression of miR‐10b‐5p, PTEN (phosphatase and tensin homolog), and HIF‐1α (hypoxia‐inducible factor 1α) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR‐10b‐5p, overexpression lentiviruses were made in the areas surrounding the
MI
sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR‐10b‐5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and
PTEN
expression. Meanwhile,
PTEN
as a target of miR‐10b‐5p was verified via luciferase reporter gene assays. Cotransfection of miR‐10b‐5 and
PTEN
verified the relationship between miR‐10b‐5 and
PTEN
. Under hypoxic stress, the expression of
HIF
‐1α and miR‐10b‐5p was examined. The results showed that miR‐10b‐5p expression was markedly reduced in the infarct border zone. Overexpression of miR‐10b‐5p in the murine model of
MI
significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR‐10b‐5p in vitro antagonized hypoxia‐induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis‐related gene
PTEN
, but overexpression of
PTEN
weakened these effects. We also found that hypoxia‐induced accumulation of
HIF
‐1α resulted in decreased expression of miR‐10b‐5p. Interfering with the activation of the
HIF
‐1α signaling pathway promoted Pri‐miR‐10b and miR‐10b‐5p expression and inhibited
PTEN
expression.

Conclusions

MicroRNA miR‐10b‐5p antagonizes hypoxia‐induced cardiomyocyte apoptosis, indicating that miR‐10b‐5p may serve as a potential future clinical target for the treatment of
MI
.
Paul’s Attitude at Athens (Acts 17:16–34)
Authors: Duniya Reuben E. 
Published: September 2019

Abstract
Commentators have interpreted Acts 17:16–34 in various ways. George Otis’s choice to associate Paul’s attitude and activity at Athens with spiritual mapping is an invitation to have another look at that text. Paul, being a human like anyone else, had background influences informing his perception of the images he saw at Athens. Whether this background influence is sufficient to interpret Paul’s response as an expression of cultural naiveté on the one hand or as spiritual mapping on the other depends on the textual data and background information available to us from his Jewish background and from evidence about the culture and thought of the first-century Greco-Roman world in which Paul lived. This article concludes that Paul was not expressing cultural naiveté at Athens, though it would be a stretch also to conclude that his action was spiritual mapping in the manner in which the concept is understood today even when lessons can be drawn from it for today’s practice.
Why Do Precipitation Intensities Tend to Follow Gamma Distributions?
Authors: Martinez-Villalobos Cristian , Neelin J. David 
Published: September 2019

AbstractThe probability distribution of daily precipitation intensities, especially the probability of extremes, impacts a wide range of applications. In most regions this distribution decays slowly with size at first, approximately as a power law with an exponent between 0 and −1, and then more sharply, for values larger than a characteristic cutoff scale. This cutoff is important because it limits the probability of extreme daily precipitation occurrences in current climate. There is a long history of representing daily precipitation using a gamma distribution—here we present theory for how daily precipitation distributions get their shape. Processes shaping daily precipitation distributions can be separated into nonprecipitating and precipitating regime effects, the former partially controlling how many times in a day it rains, and the latter set by single-storm accumulations. Using previously developed theory for precipitation accumulation distributions—which follow a sharper power-law range (exponent &lt; −1) with a physically derived cutoff for large sizes—analytical expressions for daily precipitation distribution power-law exponent and cutoff are calculated as a function of key physical parameters. Precipitating and nonprecipitating regime processes both contribute to reducing the power-law range exponent for the daily precipitation distribution relative to the fundamental exponent set by accumulations. The daily precipitation distribution cutoff is set by the precipitating regime and scales with moisture availability, with important consequences for future distribution shifts under global warming. Similar results extend to different averaging periods, providing insight into how the precipitation intensity distribution evolves as a function of both underlying physical climate conditions and averaging time.
Re-Examining the First Climate Models: Climate Sensitivity of a Modern Radiative–Convective Equilibrium Model
Authors: Kluft Lukas , Dacie Sally , Buehler Stefan A. , Schmidt Hauke , Stevens Bjorn 
Published: September 2019

Abstract
We revisit clear-sky one-dimensional radiative–convective equilibrium (1D-RCE) and determine its equilibrium climate sensitivity to a CO2 doubling (ECS) and associated uncertainty. Our 1D-RCE model, named konrad, uses the Rapid Radiative Transfer Model for GCMs (RRTMG) to calculate radiative fluxes in the same way as in comprehensive climate models. The simulated radiative feedbacks are verified by a line-by-line radiative transfer model, with which we also investigate their spectral distribution. Changing the model configuration of konrad enables a clear separation between the water vapor and the lapse rate feedbacks, as well as the interaction between the two. We find that the radiative feedback and ECS are sensitive to the chosen relative humidity profile, resulting in an ECS range of 2.09–2.40 K. Using larger CO2 forcings we find that the radiative feedback changes up to 10% for surface temperatures of 291–299 K. Although the ECS is similar to previous studies, it arises from the compensation of a larger clear-sky forcing (4.7 W m−2) and more strongly negative feedbacks (−2.3 W m−2 K−1). The lapse rate feedback and the feedback from the interaction of lapse rate and humidity compensate each other, but the degree of compensation depends on the relative humidity profile. Additionally, the temperature profile is investigated in a warming climate. The temperature change at the convective top is half as large as at the surface, consistent with the proportionally higher anvil temperature hypothesis, as long as the humidity is consistently coupled to the temperature profile.
Midlatitude Fronts and Variability in the Southern Hemisphere Tropical Width
Authors: Rudeva Irina , Simmonds Ian , Crock David , Boschat Ghyslaine 
Published: September 2019

AbstractThis study examines the relationship between midlatitude synoptic activity and variations in the width of the tropics in the Southern Hemisphere for the period 1979–2016. The edge of the tropical belt is defined here in terms of the latitude of the subtropical ridge (STR) of sea level pressure, and eddy activity in the midlatitudes is characterized by the behavior of atmospheric fronts. It is shown that the location and intensity of the STR are significantly correlated with the number of cold fronts between 20° and 40°S and that these relationships exhibit seasonal and zonal asymmetry. The link between the STR and the number of fronts is analyzed in five sectors of the Southern Hemisphere to reveal regional differences in their behavior and relationship with the southern annular mode. Some earlier studies on the widening of the tropics suggest that such changes may be caused by a shift in the location of midlatitude eddies. Our analysis explores the connection between these on a synoptic time scale. It shows that the variability of the width of the tropics is indeed strongly influenced by changes in the midlatitude synoptic activity, and that changes in synoptic activity lead those in the edge of the tropical belt by approximately one day.
Haematocrit differences modify the association of cardiopulmonary bypass reoxygenation with acute kidney injury after paediatric Tetralogy of Fallot repair
Authors: Liu Hong , Zheng Si-qiang , Qian Si-chong , He Huang-he , Xue Jin-rong 
Published: September 2019

Background: Little is known regarding the potential impact of haematocrit differences in the association between cardiopulmonary bypass reoxygenation and acute kidney injury following Tetralogy of Fallot repair. Methods: We investigated the association of perfusate oxygenation during aortic occlusion associated with acute kidney injury between 204 normal and 248 higher haematocrit children with Tetralogy of Fallot, aged 1 month-18 years, who were surgically repaired in 2012-2018. Normal and higher haematocrit children were defined as having a preoperative haematocrit within and above age- and sex-specific reference intervals, respectively. Acute kidney injury was determined as a binary variable according to the Kidney Disease Improving Global Outcomes criteria. Results: After adjusting for baseline and clinical covariates, a significant interaction between the haematocrit and continuous perfusate oxygenation on acute kidney injury was found (pinteraction = 0.049): a higher perfusate oxygenation was associated with a greater acute kidney injury risk among higher haematocrit children (adjusted odds ratio = 1.50, 95% confidence interval = [1.02, 2.22] per SD, p = 0.038) but not among normal haematocrit children (adjusted odds ratio = 0.91, 95% confidence interval = [0.51, 1.63] per SD, p = 0.73). After a similar adjustment, there was a marginal interaction between tertiles of perfusate oxygenation and haematocrit on acute kidney injury (pinteraction = 0.09): the middle and top tertiles of perfusate oxygenation were associated with a trend towards increased acute kidney injury risks among higher haematocrit children (adjusted odds ratio = 1.69, 95% confidence interval = [0.61, 4.66]; adjusted odds ratio = 2.25, 95% confidence interval = [0.84, 5.99], respectively) but not among normal haematocrit children (adjusted odds ratio = 1.16, 95% confidence interval = [0.46, 2.94]; adjusted odds ratio = 0.45, 95% confidence interval = [0.15, 1.36], respectively) compared with the bottom tertile. Conclusion: Preoperative haematocrit differences significantly modify the association of perfusate oxygenation with acute kidney injury, highlighting differential control of reoxygenation for different haematocrit children with Tetralogy of Fallot in the management of cardiopulmonary bypass.
Effectiveness of early rehabilitation on range of motion, muscle strength and arm function after breast cancer surgery: a systematic review of randomized controlled trials
Authors: Ribeiro Ivana Leão , Moreira Roberta Fátima Carreira , Ferrari Angélica Viana , Alburquerque-Sendín Francisco , Camargo Paula Rezende , Salvini Tania Fátima 
Published: September 2019

Objective: The objective was to evaluate the effectiveness of early rehabilitation on arm range of motion (ROM), strength and function after breast cancer surgery (BCS). Data sources: PubMed, MEDLINE, Bireme, Embase, LILACS and CINAHL databases were searched. Methods: Two independent reviewers selected randomized controlled trials evaluating women who underwent early rehabilitation to restore arm ROM, strength or function after BCS. Cochrane Collaboration recommendations and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Methodological quality was assessed by the PEDro scale. The International Classification of Functioning, Disability and Health was considered to analyze results. Effect size (ES) was calculated for clinical relevance interpretation of the outcomes of interest, and the evidence was summarized through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Up to June 2019, a total of 1658 references were identified and 15 studies were included. Twelve of them presented adequate methodological quality. A total of 1710 patients were evaluated. Few studies performed the simultaneous assessment of variables related to body structure and function and patient-reported outcomes. A moderate level of evidence was synthesized regarding the effectiveness of ROM exercises for improving arm flexion, abduction and external rotation (ES: 0.45–2.5). A low level of evidence was synthesized regarding the effectiveness of isolated strengthening exercises for patient-reported arm function. ROM exercises associated with muscle strengthening exhibited a moderate level of evidence for improving shoulder flexion (ES: 1.4–2.4). Conclusion: Both ROM and strengthening exercises associated with ROM exercises improved shoulder flexion, abduction and external rotation ROM after BCS. Shoulder abduction and external rotation showed less recovery, irrespective of the intervention applied.
Preexisting Cerebral Abnormalities and Functional Outcomes After Acute Ischemic Stroke
Authors: Qu Jian-Feng , Chen Yang-Kun , Zhong Huo-Hua , Li Wei , Lu Zhi-Hao 
Published: September 2019

Purpose: The aim of this study was to investigate the association between preexisting cerebral abnormalities in patients with acute ischemic stroke upon their functional outcomes. Methods: We recruited 272 patients with first-ever acute ischemic stroke. Cerebral abnormalities on magnetic resonance imaging included infarction, silent brain infarcts (SBI), enlarged perivascular spaces, white matter lesions (WMLs), global brain atrophy, and medial temporal lobe atrophy (MTLA). Functional outcomes were assessed using the instrumental activities of daily living (IADL) scale and basic activities of daily living (BADL) scale, at 3 and 6 months after the index stroke. Results: Two hundred and fifty patients completed the 3-month follow-up and 246 patients completed the 6-month follow-up. Univariate analyses showed that patients with poor IADL and BADL were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, more frequent atrial fibrillation, and large artery atherosclerosis subtypes. They also had more frequent cortical infarcts, subcortical infarcts, infratentorial infarcts, larger infarct volume, more frequent presence of SBI, severe WMLs, and MTLA. In multiple regression analyses, NIHSS on admission, subcortical region infarct and MTLA were significant predictors of poor IADL at 3 months. National Institutes of Health Stroke Scale on admission, SBI and MTLA were significant predictors of poor IADL at 6 months. National Institutes of Health Stroke Scale on admission and MTLA were significant predictors of poor BADL at 3 months. National Institutes of Health Stroke Scale on admission and SBI were significant predictors of poor BADL at 6 months. Conclusions: In patients with acute ischemic stroke, the presence of SBI, and severe MTLA represent significant predictors of poorer functional outcomes, thus highlighting the importance of preexisting cerebral abnormalities.
Antipsychotic Polypharmacy in Older Adult Asian Patients With Schizophrenia: Research on Asian Psychotropic Prescription Pattern
Authors: Dong Min , Zeng Liang-Nan , Zhang Qinge , Yang Shu-Yu , Chen Lian-Yu , Sim Kang , He Yan-Ling , Chiu Helen Fung-Kum , Sartorius Norman , Tan Chay-Hoon , Chong Mian-Yoon , Shinfuku Naotaka , Lin Shih-Ku , Ng Chee H. , Ungvari Gabor S. , Xiang Yu-Tao 
Published: September 2019

Background and Objective: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. Methods: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. Results: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses ( P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness ( P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics ( P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics ( P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics ( P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. Conclusion: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.
Impact of an electronic health record transition on chemotherapy error reporting
Authors: Hess Elizabeth , Palmer Shannon E , Stivers Andrew , Amerine Lindsey B 
Published: September 2019

Background Incident reporting systems allow for frontline employees to report errors and are a critical component of healthcare patient safety programs. Although incident reporting systems cannot quantify total errors, organizations can utilize incident reporting systems to help identify risks and trends to act upon. The objective of this article is to utilize incident reporting systems to evaluate trends in medication error reporting before and after implementation of a new electronic health record system. Methods A five-month pre- and post-analysis was completed in a cancer hospital following electronic health record conversion by reviewing medication errors reported via the institution’s voluntary incident reporting systems. Error reports included medication error category, date error was reported/occurred, patient location at time of error, harm severity score, medication(s) involved, medication use system node error originated/discovered in, medication source, narrative summary, and contributing factors. Data were analyzed using descriptive statistics within Office Excel. Results Oncology medication error reports submitted pre- and post-electronic health record were 68 vs. 57, respectively. During the pre- and post-electronic health record conversion, a majority of errors had a harm severity index of 0 or 1; 12 (18%) in pre-electronic health record and 3 (5%) in post-electronic health record were level 2, and one (1%) in pre-electronic health record vs. 0 in post-electronic health record were level 3. Reported medication errors originated most commonly during the prescribing, administration, and preparation/dispensing phase and were primarily identified in the administration phase of the medication use process. The most frequently reported error category was ‘wrong dose’ followed by ‘other’ and ‘overdose’ in the pre-electronic health record phase and ‘missing dose/delayed delivery’ and ‘order incorrect’ in the post-electronic health record phase. The most frequently reported medications included methotrexate, chemotherapy (unspecified), and cisplatin. Conclusion Analyzing data from incident reporting system reports allowed our institution to understand different trends of reporting in the cancer hospital following electronic health record adoption. Utilization of incident reporting systems must be combined with proactive risk identification approaches to enable systems-focused improvements to improve patient safety.