bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of virtual adjunctive cognitive remediation therapy on cognitive flexibility and treatment outcomes in comorbid anorexia nervosa and exercise dependence as quantified using novel biomarkers: A stage 1 registered report
Authors: Miller McKenzie L. , Sanzari Christina M. , Timko C. Alix , Hormes Julia M. 
Published: March 2023

AbstractObjectiveAnorexia nervosa (AN) is associated with significant individual mental and physical suffering and public health burden and fewer than half of patients recover fully with current treatments. Comorbid exercise dependence (ExD) is common in AN and associated with significantly worse symptom severity and treatment outcomes. Research points to cognitive inflexibility as a prominent executive function inefficiency and transdiagnostic etiologic and maintaining mechanism linking AN and ExD. This study will evaluate the initial efficacy of adjunctive Cognitive Remediation Therapy (CRT), which has been shown to produce cognitive improvements in adults with AN, in targeting cognitive inflexibility in individuals with comorbid AN and ExD. As an exploratory aim, this study also addresses the current lack of quick and cost‐effective assessments of cognitive flexibility by establishing the utility of two proposed biomarkers, heart rate variability and salivary oxytocin.MethodWe will conduct a single‐group, within‐subjects trial of an established CRT protocol delivered remotely as an adjunct to inpatient or intensive outpatient treatment as usual (TAU) to adult patients (n = 42) with comorbid AN and ExD. Assessments, including self‐report, neuropsychological, and biomarker measurements, will occur at three time points.ResultsWe expect CRT to increase cognitive flexibility transdiagnostically and consequently, along with TAU, positively impact AN and ExD compulsivity and symptom severity, including weight gain.DiscussionFindings will inform the development of more effective integrative interventions for AN and ExD targeting shared mechanisms and facilitate the routine assessment of cognitive flexibility as a transdiagnostic risk and maintaining factor across psychopathologies in clinical and research settings.Public SignificancePatients with anorexia nervosa often engage in excessive exercise, leading to harmful outcomes, including increased suicidal behavior. This study examines the preliminary efficacy of an intervention that fosters flexible and holistic thinking in patients with problematic eating and exercise to, along with routine treatment, decrease harmful exercise symptoms. This study also examines new biological markers of the inflexible thinking style thought to be characteristic of anorexia nervosa and exercise dependence.
Deep phenotype characterization of hypertensive response to exercise: implications on functional capacity and prognosis across the heart failure spectrum
Authors: Pugliese Nicola Riccardo , De Biase Nicolò , Del Punta Lavinia , Balletti Alessio , Armenia Silvia , Buralli Simona , Mengozzi Alessandro , Taddei Stefano , Metra Marco , Pagnesi Matteo , Borlaug Barry A. , Williams Bryan , Masi Stefano 
Published: March 2023

AbstractAimsLimited evidence is available regarding the role of hypertensive response to exercise (HRE) in heart failure (HF). We evaluated the systolic blood pressure (SBP) to workload slope during exercise across the HF spectrum, investigating haemodynamic and prognostic correlates of HRE.Methods and resultsWe prospectively enrolled 369 patients with HF Stage C (143 had preserved [HFpEF], and 226 reduced [HFrEF] ejection fraction), 201 subjects at risk of developing HF (HF Stages A–B), and 58 healthy controls. We performed a combined cardiopulmonary exercise stress echocardiography testing. We defined HRE as the highest sex‐specific SBP/workload slope tertile in each HF stage. Median SBP/workload slope was 0.53 mmHg/W (interquartile range 0.36–0.72); the slope was 39% steeper in women than men (p < 0.0001). After adjusting for age and sex, SBP/workload slope in HFrEF (0.47, 0.30–0.63) was similar to controls (0.43, 0.35–0.57) but significantly lower than Stages A–B (0.61, 0.47–0.75) and HFpEF (0.63, 0.42–0.86). Patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction. After a median follow‐up of 16 months, HRE was independently associated with adverse outcomes (all‐cause mortality and hospitalization for cardiovascular reasons: hazard ratio 2.05, 95% confidence interval 1.81–5.18), while rest and peak SBP were not. Kaplan–Meier analysis confirmed a worse survival probability in Stages A–B (p = 0.005) and HFpEF (p < 0.001), but not HFrEF.ConclusionA steeper SBP/workload slope is associated with impaired functional capacity across the HF spectrum and could be a more sensitive predictor of adverse events than absolute SBP values, mainly in patients in Stages A–B and HFpEF.
Scale modeling of thermo‐structural fire tests
Authors: Gangi Michael J. , Lattimer Brian Y. , Case Scott W. 
Published: March 2023

AbstractStandard methods for fire resistance testing require large‐scale assemblies and are typically conducted on specialized furnaces at considerable cost. This research focused on developing a scaling methodology for a reduced‐scale fire resistance test that reduces the size of the test article while maintaining the same thermal and structural response exhibited in the large‐scale test. The developed scaling methodology incorporates uniform geometric scaling, Fourier number time scaling, and furnace boundary condition matching. The scaling laws were experimentally validated with fire exposure tests on gypsum wallboard samples at three scales (full‐scale, 1/2‐scale, and 1/6‐scale). In the tests, samples were exposed to a full‐scale equivalent of 60‐min of ASTM E119 fire curve exposure on a reduced‐scale horizontal furnace, and the temperature rise through the thickness profile was measured. Models were created to calculate the modified fire curves for the smaller‐scale tests. Experimental results show that on the exposed surface, the 1/2‐scale absolute temperature was within 1.7% of full‐scale, while the 1/6‐scale temperature was within 2.5%. While the time‐dependent properties of burning and cracking caused visual differences in these gypsum tests, modeling and temperature measurements demonstrated that the test results were thermally similar. The good similarity of temperatures is achievable in fire exposure tests of non‐combustible gypsum wallboard down to 1/6‐scale.
Glioblastoma with novel EGFR mutations (T790M and exon 20 insertion) yet unresponsive to osimertinib: A case report
Authors: Boongird Atthaporn , Lekcharoensombat Nopphon , Jinawath Artit , Theparee Talent , Jittapiromsak Nutchawan , Shuangshoti Shanop , Thorner Paul Scott , Teerapakpinyo Chinachote 
Published: March 2023

AbstractGlioblastoma (GBM) is a high‐grade adult‐type IDH‐wildtype diffuse glioma, commonly harboring epidermal growth factor receptor (EGFR) amplification. Here, we describe a case of a 49‐year‐old man with a GBM harboring a TERT promoter mutation. Despite surgical and chemoradiation therapy, the tumor recurred. At that time, comprehensive genomic profiling by next‐generation sequencing identified two rare mutations in EGFR: T790M and an exon 20 insertion. Based on these findings, the patient elected to undergo off‐label therapy with osimertinib, a third‐generation EGFR tyrosine kinase inhibitor that has shown promising results in non‐small cell lung carcinoma, including metastatic to brain, with exactly the same EGFR mutations. Moreover, the drug has excellent central nervous system penetration. Even so, no clinical response was observed, and the patient succumbed to the disease. The lack of response may be related to the specific nature of the EGFR mutations, and/or other unfavorable tumor biology overriding any benefit from osimertinib.
How can entrepreneurs experience inform responsible health innovation policies? A longitudinal case study in Canada and Brazil
Authors: Lehoux Pascale , Silva Hudson Pacifico , Miller Fiona , Denis Jean‐Louis , Pozelli Renata Sabio 
Published: March 2023

AbstractAimTo foster equity and make health systems economically and environmentally more sustainable, Responsible Innovation in Health (RIH) calls for policy changes advocated by mission‐oriented innovation policies. These policies focus, however, on instruments to foster the supply of innovations and neglect health policies that affect their uptake. Our study's aim is to inform policies that can support RIH by gaining insights into RIH‐oriented entrepreneurs' experience with the policies that influence both the supply of, and the demand for their innovations.MethodsWe recruited 16 for‐profit and not‐for‐profit organisations engaged in the production of RIH in Brazil and Canada in a longitudinal multiple case study. Our dataset includes three rounds of interviews (n = 48), self‐reported data, and fieldnotes. We performed qualitative thematic analyses to identify across‐cases patterns.FindingsRIH‐oriented entrepreneurs interact with supply side policies that support technology‐led solutions because of their economic potential but that are misaligned with societal challenge‐led solutions. They navigate demand side policies where market approval and physician incentives largely condition the uptake of technology‐led solutions and where emerging policies bring some support to societal challenge‐led solutions. Academic intermediaries that bridge supply and demand side policies may facilitate RIH, but our findings point to an overall lack of policy directionality that limits RIH.ConclusionAs mission‐oriented innovation policies aim to steer innovation towards the tackling of societal challenges, they call for a major shift in the public sector's role. A comprehensive mission‐oriented policy approach to RIH requires policy instruments that can align, orchestrate, and reconcile health priorities with a renewed understanding of innovation‐led economic development.
Hepatitis C treatment program in Maputo, Mozambique, the challenge of genotypes and key populations: A 5‐year retrospective analysis of routine programmatic data
Authors: Loarec Anne , Gutierrez Ana Gabriela , Muvale Gil , Couto Aleny , Nguyen Aude , Yerly Sabine , Pinto Yolanda , Madeira Natercia , Gonzales Alan , Molfino Lucas , Ciglenecki Iza , Antabak Natalia Tamayo 
Published: March 2023

AbstractBackground and AimsHepatitis C (HCV) programs face challenges, especially linked to key populations to achieve World Health Organization (WHO) goals of eliminating hepatitis. Médecins Sans Frontières and Mozambique's Ministry of Health first implemented HCV treatment in Maputo, in 2016 and harm reduction activities in 2017.MethodsWe retrospectively analyzed routine data of patients enrolled between December 2016 and July 2021. Genotyping was systematically requested up to 2018 and subsequently in cases of treatment failure. Sustainable virological response was assessed 12 weeks after the end of treatment by sofosbuvir‐daclatasvir or sofosbuvir‐velpatasvir.ResultsTwo hundred and two patients were enrolled, with 159 (78.71%) males (median age: 41 years [interquartile range (IQR): 37.10, 47.00]). Risk factors included drug use (142/202; 70.29%). One hundred and eleven genotyping results indicated genotype 1 predominant (87/111; 78.37%). Sixteen patients presented genotype 4, with various subtypes. The people who used drugs and HIV coinfected patients were found more likely to present a genotype 1. Intention‐to‐treat analysis showed 68.99% (89/129) cure rate among the patients initiated and per‐protocol analysis, 88.12% (89/101) cure rate. Nineteen patients received treatment integrated with opioid substitution therapy, with a 100% cure rate versus 59.37% (38/64) for initiated ones without substitution therapy (p < 0.001). Among the resistance testing performed, NS5A resistance‐associated substitutions were found in seven patients among the nine tested patients and NS5B ones in one patient.ConclusionWe found varied genotypes, including some identified as difficult‐to‐treat subtypes. People who used drugs were more likely to present genotype 1. In addition, opioid substitution therapy was key for these patients to achieve cure. Access to second‐generation direct‐acting antivirals (DAAs) and integration of HCV care with harm reduction are crucial to program effectiveness.
A High‐Valent Ru−PCP Pincer Catalyst for the Hydrogenation of Organic Carbonates
Authors: Mujahed Shrouq , Richter Maria S. , Kirillov Evgueni , Hey‐Hawkins Evamarie , Gelman Dmitri 
Published: March 2023

AbstractIn this communication, we report on the successful application of a high‐valent RuIV bifunctional catalyst (1) for mild hydrogenation of cyclic and acyclic carbonates. Our experimental and theoretical studies suggest that the hydrogenation mechanism is operated by an unusual formally zwitterionic RuIV complex. According to our hypothesis, the positively charged high‐valent metal center is responsible for stronger hydrogen coordination. On the other hand, the proximate negatively charged ligand site facilitates heterolytic H2 bond activation, which leads to efficient catalysis.
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
Authors: Liu Haixia , Chen Xiaohui , Jia Yimin , Chen Hengyi , Wang Xiaohui , Liu Guoxiang , Luo Yang 
Published: March 2023

AbstractBRCA1/2 gene mutations, which result in a dysfunction of homologous recombination repair, have been discovered in at least 5% of breast cancer (BC) patients with the increase in BC incidence in recent years. PARP inhibitors (PARPis), the first drugs with clinical approval based on synthetic lethality, have been approved to treat BRCA1/2‐mutant BC. However, as with other targeted drugs, PARPis drug resistance has become a significant obstacle in the application of PARPis. In this paper, we discuss the mechanism of PARPis, the clinical application of PARPis as monotherapy and the possible induced resistance mechanism. By exploring the resistance mechanism, we aimed to identify appropriate effective therapeutic techniques to overcome PARPis resistance and improve the efficacy of PARPis as well as to provide theoretical and experimental evidence for the clinical use of PARPis in BRCA1/2‐mutant BC.
Single‐molecule tethered particle motion to study protein‐DNA interaction
Authors: Fan Hsiu‐Fang 
Published: March 2023

AbstractSingle‐molecule techniques have been demonstrated as powerful tools to investigate individual protein‐DNA interactions that are difficult to access by conventional biochemical techniques. These methods are popularly used to obtain valuable and detailed molecular mechanisms of enzyme functions. Currently, we have used single‐molecule tethered particle motion to investigate protein‐DNA interactions, including homologous recombination, site‐specific recombination, DNA package, and the nucleosome remodeling process, and useful information was obtained. Here, we will describe the experimental designs and present the information obtained.
Variability in sickle cell knowledge by sickle cell status
Authors: Gilpin‐Macfoy Fiona , Perilla Mindy J. , Koehly Laura M. 
Published: March 2023

AbstractDisease‐specific knowledge allows individuals with sickle cell disease, sickle cell trait, and unaffected family members alike to make informed decisions and support those affected by the condition. The current study assesses how sickle cell knowledge varies by disease status within families affected by sickle cell disease. One hundred seventy‐nine participants from 84 families completed an online survey and telephone interview. Generalized linear models, with generalized estimating equations, were fitted to evaluate differences in both item‐level responses and total scores on the Sickle Cell Knowledge Scale by sickle cell status. Those with negative or unknown sickle cell status scored significantly lower than those with sickle cell disease or trait, despite being related to someone with sickle cell disease (χ2 (2) = 9.72, p = 0.008). Overall, participants performed poorly on items related to sickle cell trait, with limited understanding of autosomal recessive inheritance patterns. The study's findings suggest a need to move beyond patient‐centered approaches to family‐centered education efforts that reach those with sickle cell traits and negative or unknown status. Findings point to knowledge gaps related to sickle cell trait and patterns of inheritance, representing key enhancement areas for future sickle cell education efforts.
On deeply critical oriented cliques
Authors: Duffy Christopher , Pavan P. D. , Sandeep R. B. , Sen Sagnik 
Published: March 2023

AbstractIn this work we consider arc criticality in colourings of oriented graphs. We study deeply critical oriented graphs, those graphs for which the removal of any arc results in a decrease of the oriented chromatic number by 2. We prove the existence of deeply critical oriented cliques of every odd order , closing an open question posed by Borodin et al. Additionally, we prove the nonexistence of deeply critical oriented cliques among the family of circulant oriented cliques of even order.
Decline in annual survival of American oystercatchers wintering in Florida linked to extreme high tides
Authors: Griffin Cody P. , Brush Janell M. , Schwarzer Amy C. 
Published: March 2023

AbstractThe projected effects of climate change include an increase in the frequency and intensity of storm events and sea‐level rise, which can erode and degrade coastal habitats and affect coastal‐dependent species. The American oystercatcher (Haematopus palliatus) is a shorebird that is dependent on low‐lying coastal habitats for breeding and wintering and is particularly vulnerable to the effects of climate change and sea‐level rise. We investigated the degree to which changes in duration of flooding of roosts affected annual survival of individuals in a large wintering population of oystercatchers on the Nature Coast of Florida, USA. We used 12 years (2007–2018) of mark‐resight data from a large‐scale monitoring effort that included winter resights on Florida's Nature Coast to model the annual survival and site fidelity of sub‐adult and adult birds. High‐tide roosts are limited in number and are a potential population‐limiting factor for wintering oystercatchers. We assessed the effect of roost inundation on survival and site fidelity by incorporating the number of hours roosts were at risk of inundation during extreme higher high tide events each winter. We documented a 7.3% decline in annual survival, from 0.96 to 0.89, over the study period, and survival rates did not differ between age stages. The decline was associated with an increase in the duration of extreme higher high tides, which had a negative effect (β = −0.003; 95% CI = −0.006 to −0.001) on survival. Site fidelity varied across the study period and among age stages, with lower rates in sub‐adults (0.85; 95% CI = 0.80–0.89) than in adults (0.94; 95% CI = 0.89–0.97). The duration of nest and roost inundation are among the greatest threats to oystercatcher populations, and high‐tide roosts are an important habitat component for wintering populations on the Nature Coast. Sea‐level rise is predicted to increase, which will contribute to the increasing inundation duration of coastal habitats. Our results underscore the importance of conservation and restoration of important wintering habitats to mitigate threats to the population viability of oystercatchers in Florida and throughout their range.
Feeling exhausted: How outpatient physical therapists perceive and manage job stressors
Authors: Ferguson Jeffrey J. , Fritsch Adam , Rentmeester Casey , Clewley Derek , Young Jodi L. 
Published: March 2023

AbstractPurposeBurnout is identified as a workplace problem rather than a worker problem. However, it remains unclear what job stressors are associated with burnout among outpatient physical therapists. Thus, the primary objective of this study was to understand the burnout experiences of outpatient physical therapists. The secondary aim was to identify the relationship between physical therapist burnout and the work setting.MethodsOne‐on‐one interviews based on hermeneutics were used for qualitative analysis.Quantitative data was collected using the Maslach Burnout Inventory‐Health Services Survey (MBI‐HSS) and the Areas of Worklife Survey (AWS).ResultsQualitative analysis found participants interpreted an increased workload with no increase in wages, loss of control, and a mismatch between organizational culture and values as the main drivers of organizational stress. Professional issues such as high debt burden, low salaries, and declining reimbursement emerged as stressors. Participants showed moderate to high emotional exhaustion per the MBI‐HSS. There was a statistically significant association between emotional exhaustion and workload and control (p < 0.001). For every one‐point increase in workload, emotional exhaustion increased by 6.49 while for every one‐point increase in control, emotional exhaustion decreased by 4.17.ConclusionOutpatient physical therapists in this study felt that increased workload with a lack of incentives and inequity, coupled with a loss of control, and a mismatch between personal and organizational values were significant job stressors. Creating awareness of outpatient physical therapist's perceived stressors may play an important role in developing strategies to diminish or prevent burnout.
Time‐continuous and time‐discontinuous space‐time finite elements for advection‐diffusion problems
Authors: von Danwitz Max , Voulis Igor , Hosters Norbert , Behr Marek 
Published: March 2023

AbstractWe construct four variants of space‐time finite element discretizations based on linear tensor‐product and simplex‐type finite elements. The resulting discretizations are continuous in space, and continuous or discontinuous in time. In a first test run, all four methods are applied to a linear scalar advection‐diffusion model problem. Then, the convergence properties of the time‐discontinuous space‐time finite element discretizations are studied in numerical experiments. Advection velocity and diffusion coefficient are varied, such that the parabolic case of pure diffusion (heat equation), as well as, the hyperbolic case of pure advection (transport equation) are included in the study. For each model parameter set, the error at the final time is computed for spatial and temporal element lengths ranging over several orders of magnitude to allow for an individual evaluation of the methods' spatial, temporal, and space‐time accuracy. In the parabolic case, particular attention is paid to the influence of time‐dependent boundary conditions. Key findings include a spatial accuracy of second order and a temporal accuracy between second and third order. The temporal accuracy tends toward third order depending on how advection‐dominated the test case is, on the choice of the specific discretization method, and on the time‐(in)dependence and treatment of the boundary conditions. Additionally, the potential of time‐continuous simplex space‐time finite elements for heat flux computations is demonstrated with a piston ring pack test case and a subtractive manufacturing test case.