bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of High School and College Graduation After Sustaining a Moderate-to-Severe Traumatic Brain Injury
Authors: Wright Brittany , Venkatesan Umesh M. , Pinto Shanti M. , Gary Kelli W. , O'Neil-Pirozzi Therese M. , Kajankova Maria , Wilmoth Kristin , Kakkanatt Ashley , Dreer Laura , Juengst Shannon B. 
Published: July 2022

Objective:
To identify early predictors of US high school and college graduation after moderate-to-severe traumatic brain injury (TBI).

Setting:
Inpatient rehabilitation and community.

Participants:
TBI Model Systems participants, aged 16 to 24 years, enrolled as high school or college students at time of injury.

Design:
Prospective cohort study.

Main Measures:
Successful graduation was defined as having a diploma (high school) or an associate/bachelor's degree (college) at 1-, 2-, or 5-year follow-up. Predictors were sex, race/ethnicity, urbanicity, preinjury substance abuse, primary rehabilitation payer, and functional independence at inpatient rehabilitation discharge.

Method:
We descriptively characterized differences between those who did and did not graduate high school and college within the first 5 years postinjury and identified early predictors of successful high school and college graduation using 2 binomial logistic regressions.

Results:
Of those with known graduation status, 81.2% of high school and 41.8% of college students successfully graduated. Graduates in both groups were more often White than Black and had more functional independence at discharge. Among high school students, preinjury substance abuse was also a risk factor for not graduating, as was identifying as Hispanic or “other” race.

Conclusions:
Sociodemographic factors and disability influence graduation outcomes, requiring structural, institutional, and personal interventions for success.
Assessing the Effect of the COVID-19 Outbreak on Didactic Education and Mental Health of Physician Assistant Students in the New York City Region
Authors: Kuriakose Shinu , Timko-Swaim Lynn , Loscalzo Carina , L’Eplattenier Mark 
Published: July 2022

Introduction
COVID-19 has profoundly affected life throughout the world, and it greatly affected physician assistant (PA) education programs when the virus spread across the New York region 2 years ago. PA programs at Stony Brook University, Hofstra University, and the New York Institute of Technology were located in the epicenter of the pandemic and were forced to transition to online learning during the spring of 2020. The purpose of this study was to explore didactic PA students’ perceptions of virtual learning, their mental health status, and the challenges and unexpected benefits they have faced during this historic time.

Methods
A consent form that linked to an 11-question electronic Qualtrics survey was emailed to all didactic students enrolled in the 3 participating PA programs. The survey data were used to conduct a descriptive analysis and a Spearman’s ρ correlation analysis using SPSS 24 software.

Results
The survey response rate was 39% (89/229). The students perceived it to be more challenging to maintain the same level of academic achievement with virtual learning, although they felt they were able to meet learning objectives and be prepared for clinical clerkships. They reported experiencing greater stress, anxiety, and depression related to decreased socialization and isolation. However, the students said that their PA program provided enough support to assist with student needs, and they noted unexpected benefits of remote learning, including more time to spend with family members, increased schedule flexibility, and lower commuting costs.

Discussion
The PA students’ education and mental health were negatively affected because of the abrupt transition from in-person to virtual learning. At the height of the COVID-19 pandemic, most of the students in the 3 participating PA programs in New York were affected by the change to remote learning and the subsequent lack of socialization. PA students experienced both challenges and benefits during this unscheduled virtual learning period. While students noted increases in mental health issues, they felt supported by faculty members and prepared to start clinical rotations.
Promontory Electrocochleography Recordings to Predict Speech-Perception Performance in Cochlear Implant Recipients
Authors: Walia Amit , Shew Matthew A. , Lee David S. , Lefler Shannon M. , Kallogjeri Dorina , Wick Cameron C. , Durakovic Nedim , Fitzpatrick Douglas C. , Ortmann Amanda J. , Herzog Jacques A. , Buchman Craig A. 
Published: July 2022

Objective
1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI).

Study Design
Prospective cohort study.

Setting
Tertiary referral center.

Patients and Interventions
Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery.

Main Outcome Measure(s)
Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months.

Results
There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW (r = 0.95), just inside scala tympani (r = 0.91), and after full insertion (r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability (r
2) in consonant-nucleus-consonant at 3 months.

Conclusions
Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.
Neonatal feeding of an estrogen receptor β agonist induces external adenomyosis-like lesions in ICR mouse
Authors: Cao Yun-Lei , Wang Xi , Liu Xi-Shi , Harada Tasuku , Guo Sun-Wei 
Published: July 2022

Objective:
Despite the fact that adenomyosis is a fairly common gynecological disorder, its pathogenesis remains elusive. Several theories on the pathogenesis of adenomyosis have been proposed, but none of them has been proven experimentally. So far, the most used one is the neonatal feeding of tamoxifen (TAM) in Institute of Cancer Research/cryopreserved (ICR/CD-1) mouse. However, its underlying mechanism of action is unknown. To further delineate the mechanism of TAM-induced adenomyosis in ICR/CD-1 mouse with regard to specific estrogen receptor (ER), we conducted an experiment that neonatal mice were fed with either TAM, or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT; an ERα agonist), or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; an ERβ agonist), or G-1 (a G-protein coupled receptor 30 agonist), or just vehicle, in an attempt to tease out which specific receptor plays a dominant role in the genesis of adenomyosis induced by neonatal feeding of TAM.

Methods:
Forty female neonatal mice were randomly divided into 5 equal-sized groups: CTL (control), TAM, PPT, DPN, and G-1. Three months later, all mice were sacrificed and their uterine horns were harvested, weighed, and processed for histological evaluation.

Results:
All mice in the TAM group developed adenomyosis, so did 4 mice (50%) in the DPN group, a result that should be considered significant given that mice in the CTL group would not develop adenomyosis. No mouse in the PPT or G-1 group developed adenomyosis. Remarkably, all lesions in the DPN group were seen exclusively near the uterine serosa, which are dramatically different from that of TAM mice and reminiscent of extrinsic or external adenomyosis in humans.

Conclusions:
Neonatal feeding of DPN induces adenomyosis, but the adenomyotic lesions appear to be different from those induced by TAM. Thus, the cause of TAM-induced adenomyosis in ICR/CD-1 mouse cannot be attributable to one specific ER alone. This suggests that the extrinsic/external adenomyosis may have a pathogenesis that is different from other sub-types of adenomyosis.
Effect of pre-IVF incubation in maturation medium on oocyte maturity, fertilization, embryonic development, and clinical outcomes following embryo transfer
Authors: Li Jian-Hua , Wang Jian-Ye , Jiao Ting-Ting , Li Min , Wei Yan , Wang Ye , Cheng Yan-Bin , Zhang Shui-Wen , Tian Shuang , Chian Ri-Cheng 
Published: July 2022

Objective:
Collected human cumulus-oocyte complexes (COCs) are usually inseminated after 4 to 6 hours in in vitro fertilization (IVF) laboratories. The purpose of this study was to determine the effect of short-term pre-IVF incubation in culture medium on subsequent oocyte maturation, fertilization, and embryonic development, as well as clinical outcomes.

Methods:
Sixty patients were divided randomly into 2 groups, pre-IVF incubation for 5 hours: 1) with (+) the designed oocyte maturation medium; 2) without (−) the designed oocyte maturation medium (transferred directly to fertilization medium for 5 hours before insemination). Oocyte maturation and fertilization were assessed, and the rate of cleavage and good quality embryos were evaluated between the 2 groups on days 2 and 3, respectively. Blastocyst development was based on the remaining number of embryos on day 3, continuously cultured to day 5 after embryo transfer or frozen on day 3, and was compared between the 2 groups. Clinical pregnancy, implantation, and miscarriage rates were also compared.

Results:
Oocyte maturation rates did not differ between groups (85.8 ± 14.1% vs. 90.7 ± 9.1%). However, the range of oocyte maturation rates (58.3%–100.0%) for each patient was significantly higher in the (−) group than in the (+) pre-incubation group (71.4%–100.0%). There were no differences in fertilization rates (89.9 ± 10.0% vs. 86.5 ± 12.2%) and good quality embryos (70.8 ± 19.1% vs. 62.1 ± 23.7%) between groups; however, the blastocyst development rates were significantly different between groups (73.1 ± 20.1% vs. 58.8 ± 18.2%, P <0.05). Nevertheless, clinical pregnancy (62.5% vs. 61.1%) and implantation (46.9% vs. 47.2%) rates did not differ between groups.

Conclusions:
These results indicate that a short pre-IVF incubation time in the designed culture medium promotes oocyte maturation and embryonic development, suggesting that short pre-IVF incubation of COCs in the designed culture medium may be important for subsequent final oocyte maturation and early embryonic development.
Characterization of folic acid, 5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters: impact on pregnancy and development
Authors: Palacios Ana M. , Feiner Rachel A. , Cabrera Robert M. 
Published: July 2022

Objectives:
Folates are B vitamins that are essential for several molecular, cellular, and biological processes, including nucleotide synthesis, methylation, and methionine cycling. The physiological impacts of these processes on health also extend to cell proliferation, folate deficiency anemia, and reduction of the risk of birth defects during pregnancy. The primary objective of this study was to characterize the binding affinities of different folate forms, folic acid (FA), 5-methyltetrahydrofolate (5MTHF), and folinic acid, to the folate receptors α and β, and to the bovine milk folate binding protein. These three dietary forms of folate are found in enriched grains (FA), various fruits and leafy vegetables (folinic acid), and red blood cells (5MTHF).

Methods:
The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined.

Results:
Our results indicated that FA had the highest affinity for all folate receptors, followed by 5MTHF, and lastly, by folinic acid, examined by several orders of magnitudes.

Conclusion:
These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.
Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial
Authors: Pagano Duilio , Bosch Jaime , Tuzzolino Fabio , Oliva Elisabetta , Ekser Burcin , Zito Giovanni , Cintorino Davide , di Francesco Fabrizio , Li Petri Sergio , Ricotta Calogero , Bonsignore Pasquale , Calamia Sergio , Magro Bianca , Trifirò Gianluca , Alduino Rossella , Barbara Marco , Conaldi Pier Giulio , Gallo Alessia , Venuti Francesca , Luca Angelo , Gruttadauria Salvatore 
Published: July 2022

Background.
The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study.

Methods.
SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors’ treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications.

Results.
The trial enrolled 58 adult patients (18–65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% (P = 0.016) and 89.66% (P = 0.080) at 90 d and 86.21% (P = 0.041) and 86.2% (P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group (P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d (P = 0.017), (P = 0.015) in the simvastatin group.

Conclusions.
Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.
Deciphering the consequence of deep intronic variants: a progeroid syndrome caused by aTAPT1mutation is revealed by combined RNA/SI-NET sequencing
Authors: Nabavizadeh Nasrinsadat , Bressin Annkatrin , Chia Poh Hui , Traspas Ricardo Moreno , Escande-Beillard Nathalie , Bonnard Carine , Hojati Zohreh , Drutman Scott , Freier Susanne , El-Khateeb Mohammad , Fathallah Rajaa , Casanova Jean-Laurent , Soror Wesam , Arafat Alaa , Shboul Mohammad , Mayer Andreas , Reversade Bruno 
Published: July 2022

ABSTRACTExome sequencing has introduced a paradigm shift for the identification of germline variations responsible for Mendelian diseases. However, non-coding regions, which make up 98% of the genome, cannot be captured. The lack of functional annotation for intronic and intergenic variants makes RNA-seq a powerful companion diagnostic. Here, we illustrate this point by identifying six patients with a recessive Osteogenesis Imperfecta (OI) and neonatal progeria syndrome. By integrating homozygosity mapping and RNA-seq, we delineated a deep intronicTAPT1mutation (c.1237-52G>A) that segregated with the disease. Using patients’ fibroblasts, we document that TAPT1’s nascent transcription was not affected, indicating instead that this variant leads to an alteration of pre-mRNA processing. Predicted to serve as an alternative splicing branchpoint, this mutation causesTAPT1exon 12 skipping, creating a protein-null allele. Additionally, our study reveals dysregulation of pathways involved in collagen and extracellular matrix biology in disease-relevant cells. Overall, our work highlights the power of transcriptomic approaches in deciphering the repercussion of non-coding variants as well as in illuminating the molecular mechanisms and underlying pathways of human diseases.
MCPNet : A parallel maximum capacity-based genome-scale gene network construction framework
Authors: Pan Tony , Chockalingam Sriram P , Aluru Maneesha , Aluru Srinivas 
Published: July 2022

AbstractMotivationGene regulatory network (GRN) reconstruction from gene expression profiles is a compute- and data-intensive problem. Numerous methods based on diverse approaches including mutual information, random forests, Bayesian networks, correlation measures, as well as their transforms and filters such as data processing inequality, have been proposed. However, an effective GRN reconstruction method that performs well in all three aspects of computational efficiency, data size scalability, and output quality remains elusive. Simple techniques such as Pearson correlation are fast to compute but ignore indirect interactions, while more robust methods such as Bayesian networks are prohibitively time consuming to apply to tens of thousands of genes.ResultsWe developed MCP Score, a novel maximum-capacity-path based metric to quantify the relative strengths of direct and indirect gene-gene interactions. We further present MCPNet, an efficient, parallelized GRN reconstruction software based on MCP Score, to reconstruct networks in unsupervised and semi-supervised manners. Using synthetic and real S. cervisiae datasets as well as real A. thaliana datasets, we demonstrate that MCPNet produces better quality networks as measured by AUPR, is significantly faster than all other GRN inference software, and also scales well to tens of thousands of genes and hundreds of CPU cores. Thus, MCPNet represents a new GRN inferencing tool that simultaneously achieves quality, performance, and scalability requirements.AvailabilitySource code freely available for download at https://doi.org/10.5281/zenodo.6499748 and https://github.com/AluruLab/MCPNet, implemented in C++ and supported on Linux.Contactaluru@cc.gatech.eduSupplementary informationSupplementary data are available at Bioinformatics online.
MicroRNA-mRNA networks are dysregulated in opioid use disorder postmortem brain: further evidence for opioid-induced neurovascular alterations
Authors: Grimm Sandra L. , Mendez Emily F. , Stertz Laura , Meyer Thomas D. , Fries Gabriel R. , Gandhi Tanmay , Kanchi Rupa , Selvaraj Sudhakar , Teixeira Antonio L. , Kosten Tom , Gunaratne Preethi , Coarfa Cristian , Walss-Bass Consuelo 
Published: July 2022

AbstractTo understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function. Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues. miRNA-mRNA network analysis showed that even though miRNAs identified in BA9 and blood were fairly distinct, their target genes and corresponding enriched pathways were highly overlapping, with tube development and morphogenesis, and pathways related to endothelial cell function and vascular organization, among the dominant enriched biological processes. These findings point to robust, redundant, and systemic opioid-induced miRNA dysregulation with potential functional impact on transcriptomic changes. Further, using correlation network analysis we identified cell-type specific miRNA targets, specifically in astrocytes, neurons, and endothelial cells, associated with OUD transcriptomic dysregulation. Our refined miRNA-mRNA networks enabled identification of novel pharmaco-chemical interventions for OUD, particularly targeting the TGF beta-p38MAPK signaling pathway. Finally, leveraging a collection of control brain transcriptomes from the Genotype-Tissue Expression (GTEx) project, we identified correlation of OUD miRNA targets with TGF beta, hypoxia, angiogenesis, coagulation, immune system and inflammatory pathways. These findings support previous reports of neurovascular and immune system alterations as a consequence of opioid abuse.
“FDA-approved carbonic anhydrase inhibitors reduce Amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness”
Authors: Canepa Elisa , Parodi-Rullan Rebecca , Vazquez-Torres Rafael , Gamallo-Lana Begona , Guzman-Hernandez Roberto , Lemon Nicole L. , Angiulli Federica , Debure Ludovic , Ilies Marc A. , Østergaard Leif , Wisniewski Thomas , Gutiérrez-Jiménez Eugenio , Mar Adam C. , Fossati Silvia 
Published: July 2022

AbstractAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective cure. Cerebrovascular and neurovascular pathology are early and causal hallmarks of AD, where cerebral amyloid angiopathy (CAA), the deposition of amyloid β (Aβ) at the cerebral vasculature, is present in about 90% of cases. Our previous work has uncovered the protective effect of carbonic anhydrase (CA) inhibition against Aβ-mediated mitochondrial dysfunction, production of reactive oxygen species (ROS) and apoptosis in vascular, glial and neuronal cells in culture. Here, we tested for the first time in a transgenic model of AD and cerebrovascular amyloidosis, the TgSwDI mice, a therapeutic regimen employing the FDA-approved CA inhibitors (CAIs), methazolamide (MTZ) and acetazolamide (ATZ). These drugs are used in humans for glaucoma, high altitude sickness, and other disorders, and can cross the blood-brain barrier. We found that both CAIs were non- toxic, significantly reduced cerebral amyloidosis, vascular, microglial and astrocytic Aβ accumulation, and ameliorated cognition. MTZ and ATZ treatment prevented caspase-3 activation in endothelial cells, microglia and astrocytes, reverted capillary constriction and microhemorrhages, reduced gliosis, and induced glial pro-clearance pathways, which are likely responsible for the reduction of Aβ deposition. Notably, we unveiled a critical new druggable target, revealing that the mitochondrial isozyme CA-VB is specifically upregulated in TgSwDI mouse brains, as well as in human brains of CAA and AD (with CAA) patients. Importantly, Aβ challenge induced CA-VB overexpression in human cerebral endothelial cells, and CA-VB silencing, mimicking CAIs effects, reduced Aβ-mediated endothelial apoptosis. This work paves the way for the application of CAIs in clinical trials for AD and CAA and uncovers CA-VB as a mediator of cerebral amyloid toxicity.