bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of local heat application during exercise on gene expression related to mitochondrial homeostasis
Authors: O’Reilly Nattie , Collins Christopher , McGlynn Mark L. , Slivka Dustin 
Published: August 2021

The aim of this study was to determine the impact of local muscle heating during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (25 ± 6 yr, 177 ± 8 cm, 78 ± 16 kg, and peak aerobic capacity 45 ± 8 mL·kg–1·min–1) cycled with one leg heated (HOT) and the other serving as a control (CON). Skin and intramuscular temperatures were taken before temperature intervention (Pre), after 30 minutes (Pre30), after exercise (Post) and four hours after exercise (4Post). Muscle biopsies were taken from each leg at Pre and 4Post. Intramuscular temperature increased within HOT (34.4 ± 0.7 °C to 36.1 ± 0.5 °C, p < 0.001) and was higher than CON at Pre30 (34.0 ± 0.7 °C, p < 0.001). However, temperatures at POST were similar (HOT 38.4 ± 0.7 °C, CON 38.3 ± 0.5 °C, p = 0.661). Skin temperature was higher than CON at Post30 (30.3 ± 1.0 °C, p < 0.001) and Post (HOT 34.6 ± 0.9 °C, CON 32.3 ± 1.6 °C, p < 0.001). PGC-1α, VEGF and NRF2 mRNA increased with exercise (p < 0.05) but was not altered with heating (p > 0.05). TFAM increased after exercise with heat application (HOT, p = 0.019) but not with exercise alone (CON, p = 0.422). There was no difference in NRF1, ESRRα, or any of the mitophagy related genes in response to exercise or temperature (p > 0.05). In conclusion, TFAM is enhanced by local heat application during endurance exercise, whereas other genes related to mitochondrial homeostasis are unaffected. Novelty: The main finding of this study is that localized heating increased TFAM mRNA expression. The normal exercise-induced increased PGC-1α gene expression was unaltered by local muscle heating.
Autonomic Security Management for IoT Smart Spaces
Authors: Lin Changyuan , Khazaei Hamzeh , Walenstein Andrew , Malton Andrew 
Published: August 2021

Embedded sensors and smart devices have turned the environments around us into smart spaces that could automatically evolve, depending on the needs of users, and adapt to the new conditions. While smart spaces are beneficial and desired in many aspects, they could be compromised and expose privacy, security, or render the whole environment a hostile space in which regular tasks cannot be accomplished anymore. In fact, ensuring the security of smart spaces is a very challenging task due to the heterogeneity of devices, vast attack surface, and device resource limitations. The key objective of this study is to minimize the manual work in enforcing the security of smart spaces by leveraging the autonomic computing paradigm in the management of IoT environments. More specifically, we strive to build an autonomic manager that can monitor the smart space continuously, analyze the context, plan and execute countermeasures to maintain the desired level of security, and reduce liability and risks of security breaches. We follow the microservice architecture pattern and propose a generic ontology named Secure Smart Space Ontology (SSSO) for describing dynamic contextual information in security-enhanced smart spaces. Based on SSSO, we build an autonomic security manager with four layers that continuously monitors the managed spaces, analyzes contextual information and events, and automatically plans and implements adaptive security policies.
As the evaluation, focusing on a current BlackBerry customer problem, we deployed the proposed autonomic security manager to maintain the security of a smart conference room with 32 devices and 66 services. The high performance of the proposed solution was also evaluated on a large-scale deployment with over 1.8 million triples.
Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer
Authors: Coates James T. , Sun Sheng , Leshchiner Ignaty , Thimmiah Nayana , Martin Elizabeth E. , McLoughlin Daniel , Danysh Brian P. , Slowik Kara , Jacobs Raquel A. , Rhrissorrakrai Kahn , Utro Filippo , Levovitz Chaya , Denault Elyssa , Walmsley Charlotte S. , Kambadakone Avinash , Stone James R. , Isakoff Steven J. , Parida Laxmi , Juric Dejan , Getz Gad , Bardia Aditya , Ellisen Leif W. 
Published: August 2021

Abstract

Sacituzumab govitecan (SG), the first antibody–drug conjugate (ADC) approved for triple-negative breast cancer, incorporates the anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 (TOP1) inhibitor payload. We sought to identify mechanisms of SG resistance through RNA and whole-exome sequencing of pretreatment and postprogression specimens. One patient exhibiting de novo progression lacked TROP2 expression, in contrast to robust TROP2 expression and focal genomic amplification of TACSTD2/TROP2 observed in a patient with a deep, prolonged response to SG. Analysis of acquired genomic resistance in this case revealed one phylogenetic branch harboring a canonical TOP1E418K resistance mutation and subsequent frameshift TOP1 mutation, whereas a distinct branch exhibited a novel TACSTD2/TROP2T256R missense mutation. Reconstitution experiments demonstrated that TROP2T256R confers SG resistance via defective plasma membrane localization and reduced cell-surface binding by hRS7. These findings highlight parallel genomic alterations in both antibody and payload targets associated with resistance to SG.

Significance:
These findings underscore TROP2 as a response determinant and reveal acquired SG resistance mechanisms involving the direct antibody and drug payload targets in distinct metastatic subclones of an individual patient. This study highlights the specificity of SG and illustrates how such mechanisms will inform therapeutic strategies to overcome ADC resistance.
This article is highlighted in the In This Issue feature, p. 2355
Career of horizontal education mismatch workers: Career competency, job crafting, and work engagement
Authors: Wardani Laila Meiliyandrie Indah , Sekarini Dyah Ayu , Syaputra Rahmat Dwi , Kartikawati Mayang Safira , Dawanti Rizki , Mulia Dian Din Astuti , Malek Mohd Dahlan A. 
Published: August 2021

Education is one of many factors that has the biggest impact toward unemployment rate due to the fact that there are mismatches between educational background and the intended job, and it is named horizontal education mismatch. The employee who is run into educational mismatch condition is seen less-competent, less-qualified, and less accomplished associated with company and work engagement which should be owned by every employee, both supervisors and subordinates. The purpose of this study was to test out that Job Crafting can play a role as a relation mediator between career competencies and work engagement toward employees which run into horizontal education mismatch. This was quantitative research; with purposive sampling method to recruit the respondent. The respondent of this research was people with age range 17-65 years old and using Process v3.5 by Hayes, The Simple Mediation Model No.4. Considering the phenomenon of Horizontal Education Mismatch which has an impact on competency and work engagement. The uniqueness of this research was to pay attention to the suitability of educational background with the current occupation, which indirectly affects the competence of workers. The results of this study were in accordance with the aims and expectations of the researchers. The results of this study indicated that job crafting plays a role as a mediator in the correlation between career competencies and work engagement. Hopefully, it will be able to meet the competency needs of employees to increase employee engagement with the company.
True power loss reduction by mountain zebra, augmented bat and improved kidney search algorithms
Authors: Kanagasabai Lenin 
Published: August 2021

<p>In this paper optimal reactive power problem is solved by mountain zebra algorithm (MZA), augmented bat algorithm (AB) and improved kidney search (IKS) algorithm. In the proposed algorithm, an intermediate state has been established at first, and then explores the intermediate state in order to obtain the global optima. Iterative local search implemented in this proposed algorithm. This technique enhances the search procedure in rapid mode. Then in this work, IKS algorithm has been proposed for solving optimal reactive power problem. In initial phase, a random population of probable solutions is created and re-absorption, secretion, excretion are imitated in the search process to check various conditions entrenched to the algorithm. The algorithm has been built to advance the search even a potential solution moved to waste (W) and it will be brought back to the filtered blood (FB). Glomerular filtration rate (GFR) test is utilized to verify the fitness of kidneys. Better efficiency of the proposed MZA, AB and IKS algorithm confirmed by successful evaluation in standard IEEE 14-bus, 118-bus, and 300-bus test systems. The results show that active power loss has been reduced.</p><p> </p>
Numerical approach of riemann-liouville fractional derivative operator
Authors: Albadarneh Ramzi B. , Batiha Iqbal M. , Adwai Ahmad , Tahat Nedal , Alomari A. K. 
Published: August 2021

<p>This article introduces some new straightforward and yet powerful formulas in the form of series solutions together with their residual errors for approximating the Riemann-Liouville fractional derivative operator. These formulas are derived by utilizing some of forthright computations, and by utilizing the so-called weighted mean value theorem (WMVT). Undoubtedly, such formulas will be extremely useful in establishing new approaches for several solutions of both linear and nonlinear fractionalorder differential equations. This assertion is confirmed by addressing several linear and nonlinear problems that illustrate the effectiveness and the practicability of the gained findings.</p>
Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association
Authors: Kohno Ritsuko , Cannom David S. , Olshansky Brian , Xi Shijun Cindy , Krishnappa Darshan , Adkisson Wayne O. , Norby Faye L. , Fedorowski Artur , Benditt David G. 
Published: August 2021

Background
Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS.

Methods and Results
Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder.

Conclusions
Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.
KWReq—a new instrument for measuring knowledge work requirements of higher education graduates
Authors: Trommer Maximilian , Schaeper Hildegard , Fabian Gregor 
Published: August 2021

AbstractStarting from the observation that questionnaires for appropriately measuring the changing working conditions and requirements of the highly qualified workforce do not exist, we developed a new German-language instrument focussing on knowledge work. Based on theoretical considerations, we first identified three basic dimensions that constitute knowledge work: novelty, complexity, and autonomy. During the subsequent process of questionnaire development with higher education graduates, including a cognitive pretest, a quantitative development study, and a replication study, these dimensions were operationalised by initially 173 and finally 22 items. Confirmatory factor analysis and structural equation modelling of the data of both the development and the replication study show that the 22-item instrument validly and reliably measures novelty (4 items), complexity with three subdimensions (9 items), and autonomy, also with three subdimensions (9 items). An English version of the questionnaire is available. However, the empirical test of the English-language questionnaire as well as possible refinements of the measurement instrument, which will be discussed in the final section of the paper, are left to future research.
A roadmap to using randomization in clinical trials
Authors: Berger Vance W. , Bour Louis Joseph , Carter Kerstine , Chipman Jonathan J. , Everett Colin C. , Heussen Nicole , Hewitt Catherine , Hilgers Ralf-Dieter , Luo Yuqun Abigail , Renteria Jone , Ryeznik Yevgen , Sverdlov Oleksandr , Uschner Diane ,   for the Randomization Innovative Design Scientific Working Group, Beckman Robert A 
Published: August 2021

AbstractBackgroundRandomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available. The goal of this paper is to present a systematic roadmap for the choice and application of a restricted randomization procedure in a clinical trial.MethodsWe survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice.ResultsRestricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size.ConclusionsThe choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.
Evaluation of a geriatrics primary care model using prospective matching to guide enrollment
Authors: Smith Valerie A. , Van Houtven Courtney Harold , Lindquist Jennifer H. , Hastings Susan N. 
Published: August 2021

AbstractBackgroundFew definitive guidelines exist for rigorous large-scale prospective evaluation of nonrandomized programs and policies that require longitudinal primary data collection. In Veterans Affairs (VA) we identified a need to understand the impact of a geriatrics primary care model (referred to as GeriPACT); however, randomization of patients to GeriPACT vs. a traditional PACT was not feasible because GeriPACT has been rolled out nationally, and the decision to transition from PACT to GeriPACT is made jointly by a patient and provider. We describe our study design used to evaluate the comparative effectiveness of GeriPACT compared to a traditional primary care model (referred to as PACT) on patient experience and quality of care metrics.MethodsWe used prospective matching to guide enrollment of GeriPACT-PACT patient dyads across 57 VA Medical Centers. First, we identified matches based an array of administratively derived characteristics using a combination of coarsened exact and distance function matching on 11 identified key variables that may function as confounders. Once a GeriPACT patient was enrolled, matched PACT patients were then contacted for recruitment using pre-assigned priority categories based on the distance function; if eligible and consented, patients were enrolled and followed with telephone surveys for 18 months.ResultsWe successfully enrolled 275 matched dyads in near real-time, with a median time of 7 days between enrolling a GeriPACT patient and a closely matched PACT patient. Standardized mean differences of < 0.2 among nearly all baseline variables indicates excellent baseline covariate balance. Exceptional balance on survey-collected baseline covariates not available at the time of matching suggests our procedure successfully controlled many known, but administratively unobserved, drivers of entrance to GeriPACT.ConclusionsWe present an important process to prospectively evaluate the effects of different treatments when randomization is infeasible and provide guidance to researchers who may be interested in implementing a similar approach. Rich matching variables from the pre-treatment period that reflect treatment assignment mechanisms create a high quality comparison group from which to recruit. This design harnesses the power of national administrative data coupled with collection of patient reported outcomes, enabling rigorous evaluation of non-randomized programs or policies.
Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections
Authors: Wong Carrie P. , Delate Thomas , Hudson Elizabeth , Nguyen Julia K. , Yang Su-Jau , Abraham Mariana 
Published: August 2021

Abstract
Background
Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI.

Methods
A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect.

Results
A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides.

Conclusions
A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.
Antiplatelet drugs for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
Authors: Del Giovane Cinzia , Boncoraglio Giorgio B. , Bertù Lorenza , Banzi Rita , Tramacere Irene 
Published: August 2021

Abstract
Background
Antiplatelet drugs may prevent recurrent ischemic events after ischemic stroke but their relative effectiveness and harms still need to be clarified. Within this network meta-analysis we aimed to summarize the current evidence for using antiplatelet drugs for secondary stroke prevention.

Methods
We searched MEDLINE, EMBASE and CENTRAL up to September 2020. Randomized controlled trials (RCTs) assessing antiplatelet drugs for secondary stroke prevention were included. We did pairwise meta-analyses and network meta-analyses using random-effects models. Primary outcomes were all strokes (ischemic or hemorrhagic) and all-cause mortality.

Results
The review included 57 RCTs, 50 (n = 165,533 participants) provided data for the meta-analyses. Compared to placebo/no treatment, moderate to high-confidence evidence indicated that cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day significantly reduced the risk of all strokes (odds ratios, ORs and absolute risk difference, ARD): cilostazol 0.51 (95 % confidence interval, CI, 0.37 to 0.71; 3.6 % fewer), clopidogrel 0.63 (95 % CI, 0.49 to 0.79; 2.7 % fewer), dipyridamole + aspirin 0.65 (95 % CI, 0.55 to 0.78; 2.5 % fewer), ticagrelor 0.68 (95 % CI, 0.50 to 0.93; 2.3 % fewer), ticlopidine 0.74 (95﻿ % CI 0.59 to 0.93; 1.9 % fewer), aspirin ≤ 150 mg/day 0.79 (95 % CI, 0.66 to 0.95; 1.5 % fewer). Aspirin > 150 mg/day and the combinations clopidogrel/aspirin, ticagrelor/aspirin, also decrease all strokes but increase the risk of hemorrhagic events. Only aspirin > 150 mg/day significantly reduced all-cause mortality (OR 0.86, 95 % CI 0.76 to 0.97; ARD 0.9 %, 95 %CI 1.5–0.2 % fewer, moderate confidence). Compared to aspirin ≤ 150 mg/day, clopidogrel significantly reduced the risk of all strokes, cardiovascular events, and intracranial hemorrhage outcomes. Cilostazol also appeared to provide advantages but data are limited to the Asian population.

Conclusions
Considering the benefits and harms ratio, cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day appear to be the best choices as antiplatelet drugs for secondary prevention of patients with ischemic stroke or TIA.

Systematic review registration
PROSPERO CRD42020159896.