bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Interpretable Discovery of Heterogeneous Treatment Effectiveness: A Covid-19 Case Study
Authors: Lengerich Benjamin J. , Nunally Mark E. , Aphinyanaphongs Yin , Caruana Rich 
Published: November 2021

AbstractTesting multiple treatments for heterogeneous (varying) effectiveness with respect to many underlying risk factors requires many pairwise tests; we would like to instead automatically discover and visualize patient archetypes and predictors of treatment effectiveness using multitask machine learning. In this paper, we present a method to estimate these heterogeneous treatment effects with an interpretable hierarchical framework that uses additive models to visualize expected treatment benefits as a function of patient factors (identifying personalized treatment benefits) and concurrent treatments (identifying combinatorial treatment benefits). This method achieves state-of-the-art predictive power for Covid-19 in-hospital mortality and interpretable identification of heterogeneous treatment benefits. We first validate this method on the large public MIMIC-IV dataset of ICU patients to test recovery of heterogeneous treatment effects. Next we apply this method to a proprietary dataset of over 3000 patients hospitalized for Covid-19, and find evidence of heterogeneous treatment effectiveness predicted largely by indicators of inflammation and throm-bosis risk: patients with few indicators of thrombosis risk benefit most from treatments against inflammation, while patients with few indicators of inflammation risk benefit most from treatments against thrombosis. This approach provides an automated methodology to discover heterogeneous and individualized effectiveness of treatments.
Longitudinal associations of behavioral problems and text reading skills in school-aged children born term and preterm
Authors: Hosoki Machiko , Borchers Lauren , Marchman Virginia A. , Travis Katherine E. , Feldman Heidi M. 
Published: November 2021

A SummaryWe assessed the contribution of total behavioral problems at 6 years to text reading skills at 8 years in children born term and preterm. Birth group moderated associations among total behavioral problems and reading skills; total behavioral problems predicted reading skills in the term but not preterm group.
Improving Power and Accuracy in Randomized Controlled Trials of Pain Treatments by Accounting for Concurrent Analgesic Use
Authors: Suri Pradeep , Heagerty Patrick J. , Korpak Anna , Jensen Mark P. , Gold Laura S. , Chan Kwun C. G. , Timmons Andrew , Friedly Janna , Jarvik Jeffrey G. , Baraff Aaron 
Published: November 2021

ABSTRACTThe 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between “observed” pain intensity (the NRS, irrespective of concurrent analgesic use), and “underlying” pain intensity (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to observed pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs.
Coordinated regulation of gene expression and microRNA changes in adipose tissue and circulating extracellular vesicles in response to pioglitazone treatment in humans with type 2 diabetes
Authors: Lopez Yury O. Nunez , Casu Anna , Kovacova Zuzana , Petrilli Alejandra , Sideleva Olga , Tharp William G. , Pratley Richard E. 
Published: November 2021

AbstractPioglitazone, a PPARγ agonist, is used to treat type 2 diabetes (T2D). PPARγ is highly expressed in adipose tissue (AT), however the effects of pioglitazone to improve insulin sensitivity are also evident in other tissues. We hypothesized that pioglitazone modifies the cargo of circulating AT-derived extracellular vesicles (EVs) to alter interorgan crosstalk. We tested this in a 3-month trial in which 24 subjects with T2D who were well-controlled with diet/exercise or metformin were randomized to treatment with either pioglitazone 45 mg/day or placebo (NCT00656864). Levels of 42 adipocyte-derived EV-miRNAs were measured in plasma EVs. Levels of 5 miRNAs (i.e., miR-7-5p, miR-20a-5p, miR-92a-3p, miR-195-5p, and miR-374b-5p) were significantly downregulated in EVs in response to pioglitazone treatment relative to placebo. However, the opposite occurred for miR-195-5p in subcutaneous AT from the same participants. Changes in miRNA expression in EVs and AT correlated with changes in suppression of lipolysis and improved insulin sensitivity, among others. DICER was downregulated and exosomal miRNA sorting-related genes YBX1 and hnRNPA2B1 displayed a trend toward downregulation in AT. Furthermore, analysis of EV-miRNA targeted genes identified a network of overtargeted transcripts that changed in a coordinated manner in AT. Collectively, our results suggest that some beneficial pharmacologic effects of PIO are mediated by adipose-specific miRNA regulation and exosomal/EV trafficking.Disclosure summaryThis study was funded by program funds granted to REP by the AdventHealth Translational Research Institute. The clinical trial was supported by an investigator initiated grant to REP from Takeda Pharmaceuticals North America. REP reports grants from Hanmi Pharmaceutical Co.; grants from Janssen; consulting fees from Merck; grants, speaker fees and consulting fees from Novo Nordisk; consulting fees from Pfizer; grants from Poxel SA; grants and consulting fees from Sanofi; consulting fees from Scohia Pharma Inc.; consulting fees from Sun Pharmaceutical Industries. AC reports consulting fees from GlaxoSmithKline. Honoraria and fees for REP’s and AC’s services were paid directly to AdventHealth, a nonprofit organization. No other potential conflicts of interest relevant to this article were reported.
Metabolic evidence for distinct pyruvate pools inside plant mitochondria
Authors: Le Xuyen H. , Lee Chun-Pong , Monachello Dario , Millar A. Harvey 
Published: November 2021

AbstractThe majority of the pyruvate inside plant mitochondria is either transported into the matrix from the cytosol via the mitochondria pyruvate carrier (MPC) or synthesised in the matrix by alanine aminotransferase (AlaAT) or NAD-malic enzyme (NAD-ME). Pyruvate from these origins could mix into a single pool in the matrix and contribute indistinguishably to respiration, or they could maintain a degree of independence in metabolic regulation. Here, we demonstrated that feeding isolated mitochondria with U-13C-pyruvate and unlabelled malate enables the assessment of pyruvate contribution from different sources to TCA cycle intermediate production. Imported pyruvate is the preferred source for citrate production even when the synthesis of NAD-ME-derived pyruvate was optimised. Genetic or pharmacological elimination of MPC activity removed this preference and allowed an equivalent amount of citrate to be generated from the pyruvate produced by NAD-ME. Increasing mitochondrial pyruvate pool size by exogenous addition only affected metabolites from pyruvate transported by MPC whereas depleting pyruvate pool size by transamination to alanine only affected metabolic products derived from NAD-ME. Together, these data reveal respiratory substrate supply in plants involves distinct pyruvate pools inside the matrix that can be flexibly mixed based on the rate of pyruvate transport from the cytosol. These pools are independently regulated and contribute differentially to organic acids export from plant mitochondria.Significance statementPyruvate is the primary respiratory substrate for energy production to support plant growth and development. However, it is also the starting material of many other pathways. Prioritisation of respiratory use over other competing pathways would enable a level of control when pyruvate is delivered to mitochondria via the mitochondrial pyruvate transporter. We demonstrated the existence of two distinct pyruvate pools in plant mitochondria suggesting inner mitochondrial organisation allows metabolic heterogeneity, hence metabolic specialisation. This explains why NAD-ME flux into plant respiration is low and confirms the prominent link between imported pyruvate and energy production. This compartmentation also reveals how NAD-ME supplies substrate to the mitochondrial pyruvate exporter in plants, especially during C4 metabolism.
Interventions to prevent or delay the onset of type 2 diabetes in women with prior gestational diabetes mellitus: protocol for a living systematic review and prospective meta-analysis
Authors: Lee Vivian Yejee , Monjur Mohammad Riashad , Gupta Yashdeep , Goyal Alpesh , Di Tanna Gian Luca , Tandon Nikhil , Patel Anushka 
Published: November 2021

AbstractIntroductionGestational diabetes mellitus (GDM), once considered a transient condition during pregnancy, is now a firmly established risk factor for type 2 diabetes mellitus (T2DM). Women whose blood glucose levels do not return to normal soon after giving birth are particularly at high risk of developing established diabetes and consequent heart and blood vessel disease. Lifestyle interventions are recommended for women with GDM to prevent or delay the subsequent development of T2DM. Recent systematic reviews and meta-analyses have suggested postpartum lifestyle interventions may be beneficial in reducing the risk of developing diabetes in women with GDM, however, included studies were generally small, many had a high risk of bias and subsequent data have become available with new trials likely to complete in the next couple of years. In addition, to the best of our knowledge, formal systematic review and meta-analysis of other approaches to preventing diabetes in this population (e.g. pharmacotherapy) has not been attempted. Therefore, an updated systematic review is needed and will be formulated as a living systematic review to ensure the inclusion of emerging studies.Methods and analysisA living systematic review and a prospective meta-analysis to examine the effectiveness of postpartum interventions in reducing the risk of developing T2DM in women with recent GDM.Ethics and disseminationEthics committee approval is not required. The data included will be from published studies, and a continued living systematic review and prospective meta-analysis will occur once a year for the next five years. Results of the review will be disseminated at relevant meetings.PROSPERO registration numberCRD42021279891Strengths and limitations of this studyA living systematic review will allow continuous surveillance of emerging literature on different lifestyle interventions in women with a history of GDM and allow identification of effective strategies for diabetes prevention.We estimate considerable heterogeneity of interventions which may limit our ability to make clear conclusions.
Serological Response to BNT162b2 and ChAdOx1 nCoV-19 Vaccines in Patients with Inflammatory Bowel Disease on Biologic Therapies; A Multi-Center Prospective Study
Authors: Shehab Mohammad , Alrashed Fatema , Alfadhli Ahmad , AlOtaibi Khazna , AlSahli Abdulla , Mohammad Hussain , Cherian Preethi , Alkhair Irina , Thanaraj Thangavel Alphonse , Channanath Arshad , Ali Hamad , Abu-Farha Mohamed , Abubaker Jehad , Al-Mulla Fahd 
Published: November 2021

AbstractIntroductionImmunogenicity of SARS-CoV-2 vaccines in patients with inflammatory bowel disease (IBD) on biologics are not well studied. The goal of this study is to measure serological response to BNT162b2 and ChAdOx1 nCoV-19 vaccines in patients with IBD receiving different biologic therapies.MethodWe performed a multi-center prospective study between August 1st, 2021, and September 15th, 2021. We measured seropositivity of SARS-CoV2 antibodies, SARS-CoV-2 IgG and neutralizing antibody concentrations, in patients with IBD receiving biologic therapies between 4–10 weeks after second dose or 3-6 weeks after first dose of vaccination with BNT162b2 or ChAdOx1 nCoV-19 vaccines.ResultsThere were 126 patients enrolled (mean age, 31 years; 60% male; 71% Crohn’s disease, 29% ulcerative colitis). 92 patients were vaccinated with BNT162b2 vaccine (73%) and 34 patients with ChAdOx1 nCoV-19 vaccine (27%). The proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving 2 doses of the vaccine in patients treated with infliximab and adalimumab were 44 out of 59 patients (74.5%) and 13 out of 16 patients (81.2%), respectively. Whereas the proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving two doses of the vaccine in patients treated with ustekinumab and vedolizumab were 100% and 92.8%, respectively. In patients receiving infliximab and adalimumab, the proportion of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels after two-dose vaccination was 40 out of 59 patients (67.7%) and 14 out 16 patients (87.5%), respectively. Whereas the proportions of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels were 12 out of 13 patients (92.3%) and 13 out of 14 patients (92.8%) in patients receiving ustekinumab and vedolizumab.ConclusionThe majority of patients with IBD on infliximab, adalimumab, and vedolizumab seroconverted after two doses of SARS-CoV-2 vaccination. All patients on ustekinumab seroconverted after two doses of SARS-CoV-2 vaccine. BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 are both likely to be effective after two doses in patients with IBD on biologics. A follow up larger studies are needed to evaluate if decay of antibodies occurs over time.
A simple tool extends TIMSTOF compatibility with historic data processing tools and enables ion mobility-enhanced spectral libraries
Authors: Orsburn Benjamin C. 
Published: November 2021

AbstractTrapped ion mobility mass spectrometry is proving to be a disruptive technology in LCMS based proteomics. One primary drawback of this hardware is the lack of compatibility with the hundreds of data processing pipelines historically in use. This study describes a simple data conversion tool that “folds” the TIMSTOF ion mobility data into the MS2 fragmentation spectra allowing simple downstream processing. Little to no detriment in the assignment of peptide spectral matches is observed when “folding” the 1/k0 value into the low mass region. To demonstrate one utility of TIMS Folding, spectral libraries are provided in multiple common formats that were constructed from the same files both with and without folded ion mobility data. When new data is acquired and folded using the same parameters prior to data processing the folded ion mobility data can be used as an additional metric for peptide match confidence against folded spectral libraries.
The effect of role model teachers on students' entrepreneurial competencies and intentions
Authors: San-Martín Paula , Pérez Andrea , Fernández-Laviada Ana , Palazuelos Estefanía 
Published: November 2021

PurposeThe paper aims to provide empirical evidence on whether the identification of the teacher as a role model is truly a key factor in improving students' entrepreneurial competencies and intention.Design/methodology/approachData were obtained from a survey of 387 university students enrolled in an entrepreneurship course, who were asked to respond to the same questionnaire at the beginning and at the end of the semester. To test the proposed hypotheses, comparison of means tests for independent samples were carried out.FindingsThe results obtained confirm that students with a role model teacher perceive that entrepreneurial competencies and perceived behavioural control increase largely during the course, whilst students with a non-role model teacher perceive that their attitude towards intention decrease.Originality/valueThe “Who should teach?” question has been disregarded in previous entrepreneurship education (EE) literature. The current paper is a first step towards a better comprehension of the teacher of entrepreneurship as a role model.
Introducing a contextual lens to assessment and intervention for young people who engage in harmful sexual behaviour: an Australian case study
Authors: Rayment-McHugh Susan , Adams Dimity , McKillop Nadine 
Published: November 2021

Purpose
Intervention for young people engaging in harmful sexual behaviour has been largely based on individual-level conceptualisations and assessment. Prevention efforts reflect this individual-focus, relying primarily on offender management and justice responses. Risk of sexual abuse, however, is often situated outside the individual, within the broader social and physical systems in which young people are embedded. Lack of recognition for how contextual factors contribute to sexual abuse narrows the focus of prevention and intervention, overlooking the very contexts and circumstances in which this behaviour occurs. This paper aims to demonstrate the utility of contextual practice with young people who sexually harm, and implications for prevention.

Design/methodology/approach
An Australian case study is used to showcase the “why”, “what” and “how” of a contextual approach to assessment and treatment of young people who sexually harm.

Findings
Contextual approaches extend the focus of clinical practice beyond the individual to include the physical and social contexts that may contribute to risk. Adding a contextual lens broadens the approach to assessment, affording new opportunities to tailor the intervention to local contextual dynamics, and identifying new targets for primary and secondary prevention.

Originality/value
This is the first known attempt to extend understanding of contextual approaches to clinical assessment and intervention for young people who sexually harm, using a case study method. The case study showcases contextual assessment and intervention processes that challenge traditional thinking and practice in this field. Importantly, the case study also reveals new opportunities for primary and secondary prevention that emerge through this contextual clinical practice.
Prioritizing motivators influencing intentions to visit spiritual destinations in India: an application of analytical hierarchical process (AHP) approach
Authors: Garg Aashish , Misra Pankaj , Gupta Sanjay , Goel Pooja , Saleem Mohd 
Published: November 2021

Purpose
Spiritual tourism is becoming a significant growth area of the Indian travel market, with more Indians opting to go on pilgrimage to popular religious cities. There are many spiritual destinations where some of this life's essences can be sought to enjoy harmony and peace. The study aims to prioritize motivators driving the intentions of the tourists to visit the spiritual destination.

Design/methodology/approach
The current study applied the analytical hierarchical process, a multi-criteria decision-making technique, on the sample of visitors from all the six spiritual destinations to rank the motivational factors that drive the intentions of the tourist to visit a spiritual destination.

Findings
The study's results postulated that spiritual fulfillment motives and destination atmosphere are the top prioritized motivations, while destination attributes and secular motives emerged as the least prioritized.

Practical implications
The research study provides valuable insights to the spiritual tourism industry stakeholders to target the tourists' highly prioritized motivations to augment the visits to a particular spiritual destination.

Originality/value
Previous research has explored the motivations and modeled their relationships with tourists' satisfaction and intentions. But, the present study has applied a multi-criteria decision-making technique to add value to the existing knowledge base.
Circular product design: strategies, challenges and relationships with new product development
Authors: Aguiar Marina Fernandes , Mesa Jaime A. , Jugend Daniel , Pinheiro Marco Antonio Paula , Fiorini Paula De Camargo 
Published: November 2021

PurposeAlthough product design is a fundamental element in the transition towards the circular economy, the knowledge of practices, methods and tools oriented to circular product design has not been widely developed. This study aims to contribute to the circular economy research area by investigating and analyzing the main design approaches to circular products and their relationship to new product development.Design/methodology/approachThe authors conducted a systematic review and qualitative analysis of 120 articles. In these studies, the authors analyzed aspects such as design strategies used, the barriers to the adoption of circular product design and the relationships between the phases of new product development processes with circular product design studies.FindingsThe findings revealed that the circular product design approach has added new design strategies to those already recommended by ecodesign, such as multiple use cycles, emotional durability and biomimicry. Furthermore, the results showed that most circular product design articles focus on the planning and concept development phases of the new product development process.Originality/valueIn this article, the authors systematized the findings of an emergent research area: the development of new products for the circular economy. Its main contributions lie in the identification of design strategies, the classification of Design for X approaches, analysis of such approaches during the new product development process and discussion of their main barriers. Finally, this study presents contributions for managers and designers who are starting the transition to a circular strategy.
The rise and fall of the energy-carbon Kuznets curve: evidence from Africa
Authors: Shobande Olatunji , Asongu Simplice 
Published: November 2021

PurposeThis paper provides an analysis of the energy-carbon Kuznets curve hypothesis (CKC) using a second-generation panel methodology.Design/methodology/approachSpecifically, the authors investigate whether energy consumption, natural resources and governance explain the CKC proposition. The study’s empirical strategy is based on the Westerlund panel cointegration test, augmented mean group (AMG) and vector autoregressive (VAR) panel Granger-causality tests.FindingsThe results suggest that the CKC hypothesis is incomplete without these mechanisms, as they play a critical role in reducing carbon emissions in Africa. The authors recommend improving the environmental standards and proper regulatory and monitoring systems to reduce carbon emissions and promote sustainable development in the continent.Originality/valueThe study revisits the CKC hypothesis with particular emphasis on governance and more robust empirical estimation techniques.