bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ticagrelor Loading on ST-Elevation Myocardial Infarction: Interaction With Prodromal Angina on Infarct Size and Clinical Events
Authors: Faria João Pedro , Oliveira Pedro , Alexandre André , Couto David Sá , Costa Ricardo , Campinas Andreia , Frias André , Brochado Bruno , Santos Raquel , Silveira João , Torres Severo , Luz André 
Published: May 2023

Introduction: Ticagrelor might reduce infarct size by exerting a more potent antiplatelet effect or by promoting a potential conditioning stimulus in ST-elevation myocardial infarction (STEMI) patients. Pre-infarction angina (PIA) is an effective preconditioning stimulus that reduces ischemia-reperfusion injury. Because little is known on the interaction of PIA in STEMI-patients loaded with ticagrelor, we sought to determine if patients loaded with ticagrelor had improved clinical outcomes as compared to clopidogrel and to study if it is modulated by the presence of PIA. Methods: From 1272 STEMI patients submitted to primary percutaneous coronary intervention and treated with clopidogrel or ticagrelor from January 2008 to December 2018, 826 were analyzed after propensity score matching. Infarct size was estimated using peak creatine kinase (CK) and troponin T (TnT), and clinical impact was evaluated through cumulative major cardiac and cerebrovascular events (MACCE) at 1-year follow-up. Matched patients and their interaction with PIA were analyzed. Results: Patients loaded with ticagrelor had lower peak CK [1405.50 U/L (730.25-2491.00), P < .001] and TnT [3.58 ng/mL (1.73-6.59), P < .001)], regardless of PIA. The presence of PIA was associated with lower CK ( P = .030), but not TnT ( P = .097). There was no interaction between ticagrelor loading and PIA ( P = .788 for TnT and P = .555 for CK). There was no difference in MACCE incidence between clopidogrel or ticagrelor loading ( P = .129). Cumulative survival was also similar between clopidogrel or ticagrelor, regardless of PIA ( P = .103). Conclusion: Ticagrelor reduced infarct sizes independently and without a synergic effect with PIA. Despite reducing infarct size, clinical outcomes were similar across both groups.
Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains
Authors: Valentine Thomas R , Kratz Anna L , Kaplish Neeraj , Chervin Ronald D , Braley Tiffany J 
Published: May 2023

Background: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. Objective: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. Methods: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). Results: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) ( ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) ( ps ⩽ 0.011). Conclusions: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. Trial registration: ClinicalTrials.gov identifier: NCT02544373 ( https://clinicaltrials.gov/ct2/show/NCT02544373 ).
Regulatory compliance and readability of informed consent forms in industry-sponsored drug development clinical trials
Authors: Dukaew Nahathai , Na Takuathung Mingkwan , Sakuludomkan Wannachai , Chairaksa Kanyarat , Klinjan Preeyaporn , Morakote Nimit , Koonrungsesomboon Nut 
Published: May 2023

Background/Aims An informed consent form is essential in drug development clinical trials. This study aimed to evaluate regulatory compliance and readability of informed consent forms currently being used in industry-sponsored drug development clinical trials. Methods This descriptive, cross-sectional study evaluated the informed consent forms of industry-sponsored drug development clinical trials conducted at the Faculty of Medicine, Chiang Mai University, between 2019 and 2020. The informed consent form’s compliance with the three major ethical guidelines and regulations (i.e. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use E6(R2) Good Clinical Practice; Declaration of Helsinki; and the revised Common Rule) were analyzed. The document length and the readability scores (using Flesch Reading Ease and Flesch-Kincaid Reading Grade) were assessed. Results Of 64 reviewed informed consent forms, the average page length was 22.0 ± 7.4 pages. More than half of their length was mainly devoted to three elements: trial procedures (22.9%), risks and discomforts (19.1%), and confidentiality and the limit of confidentiality (10.1%). Although most of the required elements of the informed consent form content were included in most informed consent forms, we identified four elements with often missing information in the form: aspects of research that are experimental (n = 43, 67.2%), involvement of whole-genome sequencing (n = 35, 54.7%), commercial profit sharing (n = 31, 48.4%), and posttrial provisions (n = 28, 43.8%). Conclusion The informed consent forms in industry-sponsored drug development clinical trials were long but incomplete. Our findings draw attention to ongoing challenges in industry-sponsored drug development clinical trials, where deficient informed consent form quality continues to exist.
The Reliability of Rating via Audio-Recording Using the Mindfulness-Based Interventions: Teaching Assessment Criteria
Authors: Floyd Erin , Adler Shelley R. , Crane Rebecca S. , Brewer Judson , Moran Patricia , Richler Robert , Hartogensis Wendy , Kuyken Willem , Hecht Frederick M. 
Published: May 2023

Background The Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is an important tool for assessing teacher skill and aspects of the fidelity of mindfulness-based interventions, but prior research on and implementation of the MBI:TAC has used video recordings, which can be difficult to obtain, share for assessments, and which increase privacy concerns for participants. Audio-only recordings might be a useful alternative, but their reliability is unknown. Objective To assess evaluator perception of the rating process and inter-rater reliability of MBI:TAC ratings using audio-only recordings. Methods We prepared audio-only files from video recordings of 21 previously rated Mindfulness-Based Stress Reduction teachers. Each audio recording was rated by 3 trained MBI:TAC assessors drawn from a pool of 12 who had previously participated in rating the video recordings. Teachers were rated by evaluators who had not viewed the video recording and did not know the teacher. We then conducted semi-structured interviews with evaluators. Results On the 6 MBI:TAC domains, the intraclass correlation coefficients (ICCs) for audio recordings ranged from .53 to .69 using an average across 3 evaluators. Using a single rating resulted in lower ICCs (.27-.38). Bland-Altman plots showed audio ratings had little consistent bias compared to video recordings and agreed more closely for teachers with higher ratings. Qualitative analysis identified 3 themes: video recordings were particularly helpful when rating less skillful teachers, video recordings tended to provide a more complete picture for rating, and audio rating had some positive features. Conclusions Inter-rater reliability of the MBI:TAC using audio-only recordings was adequate for many research and clinical purposes, and reliability is improved when using an average across several evaluators. Ratings using audio-only recordings may be more challenging when rating less experienced teachers.
Neurosonography Compared to Fetal Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis on the Diagnostic Agreement and Added Value
Authors: Miratashi Yazdi Seyedeh Nooshin , Parooie Fateme , Kazemi Mohammad Ali , Shirazi Mahboobeh , Azadbakht Javid , Moradi Behnaz 
Published: May 2023

Objective: The aim of this systematic review and meta-analysis was to compare the additional value of fetal neurosonography (NS) and fetal magnetic resonance imaging (MRI) in fetuses at risk for brain anomalies. Materials and Methods: This systematic review article was conducted based on PRISMA guidelines. On January 30, 2021, a systematic search was conducted using Embase, Medline, Web of Science, Scopus, and the Cochrane Library, with no language restrictions. The purpose was to identify all articles comparing NS with fetal MRI, in cases of suspected brain abnormalities. The statistical analysis was performed using STATA-15 and Meta-Disk 1.4 software. Results: Eight articles were included in this review. The overall agreement rate between NS and MRI was 81%. Data from NS changed the management of 6% of patients, and MRI data added data to the results of NS, in 9% of cases. In cases where the fetal MRI was normal, the added value of the postnatal MRI was 4%. Conclusion: When brain abnormalities are suspected, based on NS, MRI can play a significant role in the diagnostic path by clarifying the findings and significantly increasing the detection of abnormalities, especially when abnormalities are suspected in the posterior, midline, or cortical areas of the brain.
Olutasidenib: from bench to bedside
Authors: Venugopal Sangeetha , Watts Justin 
Published: May 2023

Abstract
The discovery of isocitrate dehydrogenase 1 (IDH1) mutations in acute myeloid leukemia (AML) and the resounding success of molecularly targeted therapies in related myeloid malignancies swiftly prompted the development of IDH1mut inhibitors. Olutasidenib (formerly known as FT-2102) is an orally administered novel IDH1mut inhibitor that entered clinical development in 2016, proceeded briskly through the developmental process, and was granted regular approval to treat patients with R/R IDH1mut AML on 1 December 2022. Single agent olutasidenib, a potent and selective IDH1mut inhibitor, demonstrated highly durable remission rates along with meaningful outcomes, such as transfusion independence, in patients with R/R IDH1mut AML. This review will examine the preclinical and clinical development and the positioning of olutasidenib in the IDH1mut AML treatment landscape.
American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing
Authors: Middeldorp Saskia , Nieuwlaat Robby , Baumann Kreuziger Lisa , Coppens Michiel , Houghton Damon , James Andra H. , Lang Eddy , Moll Stephan , Myers Tarra , Bhatt Meha , Chai-Adisaksopha Chatree , Colunga-Lozano Luis E. , Karam Samer G. , Zhang Yuan , Wiercioch Wojtek , Schünemann Holger J. , Iorio Alfonso 
Published: May 2023

Background
Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial.

Objective
These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing.

Methods
ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment.

Results
The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions.

Conclusions
The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.
Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials
Authors: Chuang Min-Hsiang , Chen I-Wen , Chen Jen-Yin , Kang Fu-Chi , Ho Chun-Ning , Wu Shao-Chun , Yew Ming , Lan Kuo-Mao , Hung Kuo-Chuan 
Published: May 2023

BackgroundThe efficacy and safety of gefapixant in adults with chronic cough remain unclear. Our objective was to assess the efficacy and safety of gefapixant using updated evidence.MethodsMEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched from inception through September 2022. Subgroup analysis based on dose of gefapixant (i.e.≤20, 45–50 and ≥100 mg twice daily for low, moderate and high doses, respectively) was performed to explore a potential dose-dependent effect.ResultsFive studies involving seven trials showed the efficacy of moderate- or high-dose gefapixant for reducing objective 24-h cough frequency (estimated relative reduction 30.9% and 58.5%, respectively) (i.e.primary outcome) and awake cough frequency (estimated relative reduction 47.3% and 62.8%, respectively). Night-time cough frequency was only reduced with high-dose gefapixant. Consistently, the use of moderate- or high-dose gefapixant significantly alleviated cough severity and improved cough-related quality of life, but increased the risk of all-cause adverse events (AEs), treatment-related AEs and ageusia/dysgeusia/hypogeusia. Subgroup analysis showed dose dependency in both efficacy and AEs with a cut-off dose being ≥45 mg twice daily.ConclusionsThis meta-analysis revealed dose-dependent efficacy and adverse effects of gefapixant against chronic cough. Further studies are required to investigate the feasibility of moderate-dose (i.e.45–50 mg twice daily) gefapixant in clinical practice.
Migraine with aura: less control over pain and fragrances?
Authors: Mignot Coralie , Faria Vanda , Hummel Thomas , Frost Marie , Michel Christoph M. , Gossrau Gudrun , Haehner Antje 
Published: May 2023

Abstract
Background
Accumulating data emphasizes the importance of olfaction in migraine pathophysiology. However, there are only a few studies evaluating how the migraine brain processes olfactory stimulation, and virtually no studies comparing patients with and without aura in this context.

Methods
This cross-sectional study recorded event-related potentials from 64 electrodes during a pure olfactory or pure trigeminal stimulus in females with episodic migraine with aura (n = 13) and without aura (n = 15), to characterize the central nervous processing of these intranasal stimuli. Patients were tested in interictal state only. Data were analyzed in the time domain and in the time–frequency domain. Source reconstruction analysis was also performed.

Results
Patients with aura had higher event-related potentials amplitudes for left-sided trigeminal and left-sided olfactory stimulations, and higher neural activity for right-sided trigeminal stimulation in brain areas related to trigeminal and visual processing. Following olfactory stimulations patients with aura displayed decreased neural activity in secondary olfactory structures compared to patients without aura. Oscillations in the low frequency bands (< 8 Hz) differed between patient groups.

Conclusions
Altogether this may reflect hypersensitivity to nociceptive stimuli in patients with aura relative to patients without aura. Patients with aura have a bigger deficit in engaging secondary olfactory-related structures, possibly leading to distorted attention and judgements towards odors. The cerebral overlap between trigeminal nociception and olfaction might explain these deficits.
HISS: Snakemake-based workflows for performing SMRT-RenSeq assembly, AgRenSeq and dRenSeq for the discovery of novel plant disease resistance genes
Authors: Adams Thomas M. , Smith Moray , Wang Yuhan , Brown Lynn H. , Bayer Micha M. , Hein Ingo 
Published: May 2023

Abstract

Background
In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise.

Results
Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license.

Conclusions
HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.
Hidden diversity: DNA metabarcoding reveals hyper-diverse benthic invertebrate communities
Authors: Gleason Jennifer Erin , Hanner Robert H. , Cottenie Karl 
Published: May 2023

Abstract
Background
Freshwater ecosystems, such as streams, are facing increasing pressures from agricultural land use and recent literature stresses the importance of robust biomonitoring to detect trends in insect decline globally. Aquatic insects and other macroinvertebrates are often used as indicators of ecological condition in freshwater biomonitoring programs; however, these diverse groups can present challenges to morphological identification and coarse-level taxonomic resolution can mask patterns in community composition. Here, we incorporate molecular identification (DNA metabarcoding) into a stream biomonitoring sampling design to explore the diversity and variability of aquatic macroinvertebrate communities at small spatial scales. While individual stream reaches can be very heterogenous, most community ecology studies focus on larger, landscape-level patterns of community composition. A high degree of community variability at the local scale has important implications for both biomonitoring and ecological research, and the incorporation of DNA metabarcoding into local biodiversity assessments will inform future sampling protocols.

Results
We sampled twenty streams in southern Ontario, Canada, for aquatic macroinvertebrates across multiple time points and assessed local community variability by comparing field replicates taken ten meters apart within the same stream. Using bulk-tissue DNA metabarcoding, we revealed that aquatic macroinvertebrate communities are highly diverse at small spatial scales with unprecedented levels of local taxonomic turnover. We detected over 1600 Operational Taxonomic Units (OTUs) from 149 families, and a single insect family, the Chironomidae, contained over one third of the total number of OTUs detected in our study. Benthic communities were largely comprised of rare taxa detected only once per stream despite multiple biological replicates (24–94% rare taxa per site). In addition to numerous rare taxa, our species pool estimates indicated that there was a large proportion of taxa that remained undetected by our sampling regime (14–94% per site). Our sites were located across a gradient of agricultural activity, and while we predicted that increased land use would homogenize benthic communities, this was not supported as within-stream dissimilarity was unrelated to land use. Within-stream dissimilarity estimates were consistently high for all levels of taxonomic resolution (invertebrate families, invertebrate OTUs, chironomid OTUs), indicating stream communities are very dissimilar at small spatial scales.