bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collegiate male athletes exhibit conditions of the Male Athlete Triad
Authors: Moris J.M. , Olendorff S.A. , Zajac C.M. , Fernandez-del-Valle M. , Webb B.L. , Zuercher J.L. , Smith B.K. , Tucker K.R. , Guilford B.L. 
Published: November 2021

The primary purpose of this study was to determine prevalence of the Male Athlete Triad (MAT) conditions: low energy availability (EA), low bone mineral density (BMD), and low testosterone in male collegiate athletes from different sports. Participants included 44 collegiate male athletes (age, 20.4 ± 0.2 years; body mass index, 25.3 ± 1.3 kg/m2) from 7 sports (cross country, soccer, basketball, wrestling, track, golf, and baseball). Resting metabolic rate, 3-day food intake, 7-day exercise energy expenditure, body composition, and reproductive and metabolic hormones were assessed. Of the total participants, 15% had low EA, 0% had low BMD, 28% had low total testosterone (TT), and 80% had low calculated free testosterone (cFT). There were no significant correlations between EA, BMD, TT, and cFT. Insulin and sex hormone binding globulin (SHBG) were below and on the upper end of the reference range for healthy male adults, respectively. Insulin was negatively correlated with total (r = –0.330, p = 0.043) and lumbar spine BMD z-scores (r = –0.413, p = 0.010). Low TT and low cFT were the most prevalent MAT conditions among all athletes. Further research should investigate the relationship between insulin and SHBG and the role of these hormones in the MAT.Novelty: Assessment of energy availability alone is not sufficient to identify physiological disturbances in collegiate male athletes. Low total and/or free testosterone may be present in some collegiate male athletes, regardless of BMD status. Low insulin and high SHBG concentration may portray the presence of conditions of the MAT in male collegiate athletes.
Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms
Authors: Lindholm Malene E. , Jimenez-Morales David , Zhu Han , Seo Kinya , Amar David , Zhao Chunli , Raja Archana , Madhvani Roshni , Abramowitz Sarah , Espenel Cedric , Sutton Shirley , Caleshu Colleen , Berry Gerald J. , Motonaga Kara S. , Dunn Kyla , Platt Julia , Ashley Euan A. , Wheeler Matthew T. 
Published: November 2021

Background:

ACTN2 (alpha-actinin 2) anchors actin within cardiac sarcomeres. The mechanisms linking
ACTN2
mutations to myocardial disease phenotypes are unknown. Here, we characterize patients with novel
ACTN2
mutations to reveal insights into the physiological function of ACTN2.

Methods:
Patients harboring ACTN2 protein-truncating variants were identified using a custom mutation pipeline. In patient-derived iPSC-cardiomyocytes, we investigated transcriptional profiles using RNA sequencing, contractile properties using video-based edge detection, and cellular hypertrophy using immunohistochemistry. Structural changes were analyzed through electron microscopy. For mechanistic studies, we used co-immunoprecipitation for ACTN2, followed by mass-spectrometry to investigate protein-protein interaction, and protein tagging followed by confocal microscopy to investigate introduction of truncated ACTN2 into the sarcomeres.

Results:

Patient-derived iPSC-cardiomyocytes were hypertrophic, displayed sarcomeric structural disarray, impaired contractility, and aberrant Ca
2+
-signaling. In heterozygous indel cells, the truncated protein incorporates into cardiac sarcomeres, leading to aberrant Z-disc ultrastructure. In homozygous stop-gain cells, affinity-purification mass-spectrometry reveals an intricate ACTN2 interactome with sarcomere and sarcolemma-associated proteins. Loss of the C-terminus of ACTN2 disrupts interaction with ACTN1 (alpha-actinin 1) and GJA1 (gap junction protein alpha 1), 2 sarcolemma-associated proteins, which may contribute to the clinical arrhythmic and relaxation defects. The causality of the stop-gain mutation was verified using CRISPR-Cas9 gene editing.

Conclusions:

Together, these data advance our understanding of the role of ACTN2 in the human heart and establish recessive inheritance of
ACTN2
truncation as causative of disease.
Abstract P359: Electroconductive Scaffolds To Mature Induced Pluripotent Stem Cell-derived Cardiomyocytes For Cardiac Tissue Engineering
Authors: Cook Suh Hee T , Gluck Jessica 
Published: November 2021

Heart disease is the leading cause of death worldwide. Cardiac tissue engineering (CTE) aims to repair and replace heart tissue, offering a solution. Induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) could revolutionize CTE due to their theoretical ability to supply limitless patient-specific CMs. However, iPSC-CMs are electrophysiologically immature compared to functional adult CMs, and therefore incapable of sustaining a heartbeat.
Thus, a scaffold capable of electrophysiologically maturing iPSC-CMs is needed. My research increases the electroconductivity of electrospun (ES) scaffolds by incorporating carbon nanotubes (CNTs), which I hypothesize will mature iPSC-CMs seeded onto them due to their excellent electroconductive properties.
Morphological, biocompatibility, and electrical analyses have been performed on ES polycaprolactone (PCL) and gelatin scaffolds with CNTs incorporated via a ‘sandwich’ and dual deposition method in order to increase electroconductivity. Morphological analyses were performed via ImageJ on SEM images. Fiber diameter and pore size quantification confirmed the ability to exert morphological control by modifying solution properties and ES parameters, which is crucial to achieve biomimicry of the cardiac extracellular matrix. Live/dead assays and immunofluorescence revealed the CNT scaffolds offer high biocompatibility for NIH 3T3 fibroblasts, which attach, proliferate, and migrate well. Electrical analysis performed with a multimeter and two-probe resistance measurement confirms that inclusion of CNTs significantly increases scaffold conductivity, moreso for dual deposition scaffolds than ‘sandwich’ ones, and moreso parallel to the CNT arrays than orthogonally.

These results prove the feasibility of using such scaffolds as a method for
in vitro
electrophysiological iPSC-CM maturation. Next steps include optimization of scaffolds, analysis of iPSC-CM biocompatibility and response, and recapitulation and manipulation of the electrophysiology of cardiac tissue, including quantification of markers for cardiac function and maturity, and assessment of iPSC-CM + scaffold response to electrical pacing.
Abstract P372: Serum From Pediatric Dilated Cardiomyopathy Patients Promotes Dysregulation Of Cardiolipin Biosynthesis And Mitochondrial Dysfunction In Primary Cardiomyocytes
Authors: Pires da Silva Julie , Garcia Anastacia M , Miyano Carissa A , Sparagna Genevieve C , Jonscher Raleigh L , Elajaili Hanan B , Sucharov Carmen C 
Published: November 2021

Pediatric dilated cardiomyopathy (DCM) is a devastating and poorly understood disease with most clinical treatment paradigms extrapolated from the adult population. Our studies have demonstrated that aspects of metabolism and mitochondrial function are dysregulated in pediatric DCM hearts. Cardiolipin (CL), a unique phospholipid in the inner mitochondrial membrane, is essential for optimal mitochondrial function and was shown to be dysregulated in both the failing adult and pediatric human heart. The objective of this study is to investigate if serum circulating factors from pediatric DCM patients can remodel CL resulting in mitochondrial dysfunction
in vitro
, similar to what is observed in the failing pediatric heart.

Using a novel
in vitro
model that consists of treating neonatal rat ventricular myocytes (NRVMs) with serum from pediatric DCM patients or from non-failing (NF) healthy controls, mitochondrial respiration was assessed using the Agilent Seahorse, and reactive oxygen species (ROS) was assessed using Electron Paramagnetic Resonance Spectroscopy. Relative mitochondrial DNA (mtDNA) copy number was determined by qPCR and expression of enzymes involved in CL biosynthesis and remodeling were analyzed using RT-qPCR. Mass-spectrometry was used to quantitate total and specific CL species and to investigate the metabolite composition of NRVMs treated with NF or DCM serum.

While mitochondrial ROS and mtDNA copy number were not significantly altered, we show that DCM serum decreases mitochondrial function, which is associated with alterations in CL content and composition and the downregulation of enzymes implicated in CL biosynthesis and remodeling. Analysis of metabolite content showed an alteration of pathways involved in fatty acid metabolism, mitochondrial biogenesis and regulation of β-oxidation by the transcription factor PPARα.
In conclusion, pediatric DCM serum circulating factors can promote CL remodeling resulting mitochondrial dysfunction in primary cardiomyocytes. These findings suggest that CL could be a novel therapeutic target for this particular population.
Appropriateness of Using Vitamin K for the Correction of INR Elevation Secondary to Hepatic Disease in Critically ill Patients: An Observational Study
Authors: Al Sulaiman Khalid , Al Mutairi Mashael , Al Harbi Omar , Al Duraihim Alanoud , Aldosary Sara , Al Khalil Haifa , Al Shaya Abdulrahman , Al Harbi Shmeylan , Alotaibi Nouf , Al Aamer Kholoud , Vishwakarma Ramesh , Al Asiri Mohammed , Aljuhani Ohoud , Al Katheri Abdulmalik , Al Bekairy Abdulkareem M. 
Published: November 2021

Background Using vitamin K for correction of coagulopathy in critically ill patients is controversial with limited evidence. This study aims to evaluate the efficacy and safety of vitamin K in the correction of international normalized ratio (INR) elevation secondary to liver disease in critically ill patients. Method A retrospective study of critically ill patients with coagulopathy secondary to liver disease. The primary outcome was to evaluate the association between vitamin K administration and the incidence of new bleeding events in critically ill patients with INR elevation; other outcomes were considered secondary. Patients were categorized into two groups based on vitamin K administration to correct INR elevation. The propensity score was generated based on disease severity scores and the use of pharmacological DVT prophylaxis. Results A total of 98 patients were included in the study. Forty-seven patients (48%) received vitamin K during the study period. The odds of the new bleeding event was not statistically different between groups (OR 2.4, 95% CI 0.28-21.67, P = .42). Delta of INR reduction was observed with a median of 0.63 when the first dose is given ( P-value: <.0001). However the INR reduction with other subsequent doses of vitamin K was not statistically significant. Conclusion The administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events. Further studies are needed to assess the value of vitamin K administration in critically ill patients with liver diseases related coagulopathy.
Short report: A quantitative methodological review of participant characteristics in the literature testing mental health interventions for youth with autism spectrum disorder
Authors: Dickson Kelsey S , Galligan Megan Ledoux , Lok Ho 
Published: November 2021

There have been significant efforts to develop, adapt, and test interventions targeting the co-occurring mental health conditions common among autistic youth, with several extant narrative and systematic reviews demonstrating the efficacy of these interventions. Yet, a methodological analysis of the literature testing these interventions, particularly the characteristics of the participant samples comprising this evidence base, is needed to contextualize our current understanding of treatment effects and highlight current gaps in the current evidence base to inform future research. This systematic quantitative methodology review characterized participants included in the mental health treatment research for autistic youth. One hundred and thirty-one articles testing mental health interventions for autism spectrum disorder were coded for youth, caregiver, and provider participant demographics. Findings indicated limited representation of females, transition age youth, racial/ethnic minority groups, and youth diverse in cognitive functioning and co-occurring mental health symptoms or conditions. Limited inclusion of providers’ representative of the clinical workforce was also noted. These results illuminate several critical gaps in the current evidence base for mental health interventions for autistic youth and provide recommendations for future research directions. Lay abstract Previous research has highlighted the importance of mental health treatment for autistic youth. In that research base, most studies focus on demonstrating the efficacy of a particular intervention with a sample of autistic youth. However, understanding the characteristics of samples used within these studies (i.e. demographics) is an important avenue for expanding this research to a more diverse, representative sample of autistic youth in community settings. As such, the current review examined and characterized participants included within mental health treatment research. We coded studies for various demographics among the youth sample, caregivers, and providers participants. Results indicated that while efforts have been made to increase diversity in research, very few studies including transition-aged youth, those identifying as female, and/or those identifying as non-Caucasian. Clinically, a few studies included youth with lower cognitive abilities and/or those with specific mental health problems (e.g. trauma and depression) or more than one co-occurring mental health conditions. Overall, our results highlight several critical gaps in our current evidence base regarding mental health treatment for autistic youth, including the limited clinical representativeness of both provider and child participants.
Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma
Authors: Mohan Meera , Kendrick Samantha , Szabo Aniko , Yarlagadda Naveen , Atwal Dinesh , Pandey Yadav , Roy Arya , Parikh Richa , Lopez James , Thanendrarajan Sharmilan , Schinke Carolina , Alapat Daisy , Sawyer Jeffrey , Tian Erming , Tricot Guido , van Rhee Frits , Zangari Maurizio 
Published: November 2021

Abstract
Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10−5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.
Divergence time estimation of Galliformes based on the best gene shopping scheme of ultraconserved elements
Authors: Chen De , Hosner Peter A. , Dittmann Donna L. , O’Neill John P. , Birks Sharon M. , Braun Edward L. , Kimball Rebecca T. 
Published: November 2021

Abstract
Background
Divergence time estimation is fundamental to understanding many aspects of the evolution of organisms, such as character evolution, diversification, and biogeography. With the development of sequence technology, improved analytical methods, and knowledge of fossils for calibration, it is possible to obtain robust molecular dating results. However, while phylogenomic datasets show great promise in phylogenetic estimation, the best ways to leverage the large amounts of data for divergence time estimation has not been well explored. A potential solution is to focus on a subset of data for divergence time estimation, which can significantly reduce the computational burdens and avoid problems with data heterogeneity that may bias results.

Results
In this study, we obtained thousands of ultraconserved elements (UCEs) from 130 extant galliform taxa, including representatives of all genera, to determine the divergence times throughout galliform history. We tested the effects of different “gene shopping” schemes on divergence time estimation using a carefully, and previously validated, set of fossils. Our results found commonly used clock-like schemes may not be suitable for UCE dating (or other data types) where some loci have little information. We suggest use of partitioning (e.g., PartitionFinder) and selection of tree-like partitions may be good strategies to select a subset of data for divergence time estimation from UCEs. Our galliform time tree is largely consistent with other molecular clock studies of mitochondrial and nuclear loci. With our increased taxon sampling, a well-resolved topology, carefully vetted fossil calibrations, and suitable molecular dating methods, we obtained a high quality galliform time tree.

Conclusions
We provide a robust galliform backbone time tree that can be combined with more fossil records to further facilitate our understanding of the evolution of Galliformes and can be used as a resource for comparative and biogeographic studies in this group.
Biogeographic and demographic history of the Mediterranean snakes Malpolon monspessulanus and Hemorrhois hippocrepis across the Strait of Gibraltar
Authors: Machado Luis , Harris D. James , Salvi Daniele 
Published: November 2021

AbstractBackgroundThe contribution of North Africa to the assembly of biodiversity within the Western Palaearctic is still poorly documented. Since the Miocene, multiple biotic exchanges occurred across the Strait of Gibraltar, underlying the high biogeographic affinity between the western European and African sides of the Mediterranean basin. We investigated the biogeographic and demographic dynamics of two large Mediterranean-adapted snakes across the Strait and assess their relevance to the origin and diversity patterns of current European and North African populations.ResultsWe inferred phylogeographic patterns and demographic history ofM. monspessulanusandH. hippocrepis, based on range-wide multilocus data, combined with fossil data and species distribution modelling, under present and past bioclimatic envelopes. For both species we identified endemic lineages in the High Atlas Mountains (Morocco) and in eastern Iberia, suggesting their persistence in Europe during the Pleistocene. One lineage is shared between North Africa and southern Iberia and likely spread from the former to the latter during the sea-level low stand of the last glacial stage. During this periodM. monspessulanusshows a sudden demographic expansion, associated with increased habitat suitability in North Africa. Lower habitat suitability is predicted for both species during interglacial stages, with suitable areas restricted to coastal and mountain ranges of Iberia and Morocco. Compiled fossil data forM. monspessulanusshow a continuous fossil record in Iberia at least since the Pliocene and throughout the Pleistocene.ConclusionsThe previously proposed hypothesis of Pleistocene glacial extinction of both species in Europe is not supported based on genetic data, bioclimatic envelopes models, and the available fossil record. A model of range retraction to mountain refugia during arid periods and of glacial expansion (demographic and spatial) associated to an increase of Mediterranean habitats during glacial epochs emerges as a general pattern for mesic vertebrates in North Africa. Moreover, the phylogeographic pattern ofH. hippocrepisconforms to a well-established biogeographic partition between western and eastern Maghreb.
The whole-genome sequencing in predicting Mycobacterium tuberculosis drug susceptibility and resistance in Papua, Indonesia
Authors: Maladan Yustinus , Krismawati Hana , Wahyuni Tri , Tanjung Ratna , Awaludin Kamla , Audah Kholis Abdurachim , Parikesit Arli Aditya 
Published: November 2021

AbstractBackgroundTuberculosis is one of the deadliest disease caused byMycobacterium tuberculosis. Its treatment still becomes a burden for many countries including Indonesia. Drug resistance is one of the problems in TB treatment. However, a development in the molecular field through Whole-genome sequencing (WGS) can be used as a solution in detecting mutations associated with TB- drugs. This investigation intended to implement this data for supporting the scientific community in deeply understanding any TB epidemiology and evolution in Papua along with detecting any mutations in genes associated with TB-Drugs.ResultA whole-genome sequencing was performed on the random samples from TB Referral Laboratory in Papua utilizing MiSeq 600 cycle Reagent Kit (V3). Furthermore, TBProfiler was used for genome analysis, RAST Server was employed for annotation, while Gview server was applied for BLAST genome mapping and a Microscope server was implemented for Regions of Genomic Plasticity (RGP). The largest genome ofM. tuberculosisobtained was at the size of 4,396,040 bp with subsystems number at 309 and the number of coding sequences at 4326. One sample (TB751) contained one RGP. The drug resistance analysis revealed that several mutations associated with TB-drug resistance existed. In details, mutations ofrpoBgene which were identified as S450L, D435Y, H445Y, L430P, and Q432K had caused the reduced effectiveness of rifampicin; while the mutases inkatG(S315T),kasA(312S),inhA(I21V), and Rv1482c-fabG1(C-15 T) genes had contributed to the resistance in isoniazid. In streptomycin, the resistance was triggered by the mutations inrpsL(K43R) andrrs(A514C, A514T) genes, and, in Amikacin, its resistance was led by mutations inrrs(A514C) gene. Additionally, in Ethambutol and Pyrazinamide, their reduced effectiveness was provoked byembBgene mutases (M306L, M306V, D1024N) andpncA(W119R).ConclusionsThe results from whole-genome sequencing of TB clinical sample in Papua, Indonesia could contribute to the surveillance of TB-drug resistance. In the drug resistance profile, there were 15 Multi Drugs Resistance (MDR) samples. However, Extensively Drug-resistant (XDR) samples have not been found, but samples were resistant to only Amikacin, a second-line drug.