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Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon Jul 2021

Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon

2020-Current year OA Pubs

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as …


Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll Jul 2021

Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll

2020-Current year OA Pubs

Epigenetic regulation plays an important role in controlling gene expression during complex processes, such as development of the human brain. Mutations in genes encoding chromatin modifying proteins and in the non-protein coding sequences of the genome can potentially alter transcription factor binding or chromatin accessibility. Such mutations can frequently cause neurodevelopmental disorders, therefore understanding how epigenetic regulation shapes brain development is of particular interest. While epigenetic regulation of neural development has been extensively studied in murine models, significant species-specific differences in both the genome sequence and in brain development necessitate human models. However, access to human fetal material is limited …


Characteristics Of U.S. Acute Care Hospitals That Have Implemented Telemedicine Critical Care, Uchenna R. Ofoma, Thomas M. Maddox, Chamila Perera, R. J. Waken, Anne M. Drewry, Lei Liu, Walter Boyle, Marin Kollef, Karen E. Joynt Maddox Jul 2021

Characteristics Of U.S. Acute Care Hospitals That Have Implemented Telemedicine Critical Care, Uchenna R. Ofoma, Thomas M. Maddox, Chamila Perera, R. J. Waken, Anne M. Drewry, Lei Liu, Walter Boyle, Marin Kollef, Karen E. Joynt Maddox

2020-Current year OA Pubs

OBJECTIVES: Telemedicine critical care is associated with improved efficiency, quality, and cost-effectiveness. As of 2010, fewer than 5% of U.S. hospitals had telemedicine critical care, and fewer than 10% of ICU beds were covered. We evaluated recent telemedicine critical care implementation and bed coverage rates in the United States and compared characteristics of hospitals with and without telemedicine critical care.

DESIGN: Cross-sectional study of 2018 American Hospital Association Annual Survey Database.

SETTING: U.S. hospitals.

PATIENTS: None.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We obtained data regarding telemedicine critical care implementation, ICU capability (defined as ≥ 1 ICU bed), other hospital …


Excimer Laser Coronary Angioplasty In Coronary Lesions: Use And Safety From The Ncdr/Cath Pci Registry, Marc Sintek, Edward Coverstone, Richard Bach, Alan Zajarias, John Lasala, Howard Kurz, Kevin Kennedy, Jasvindar Singh Jul 2021

Excimer Laser Coronary Angioplasty In Coronary Lesions: Use And Safety From The Ncdr/Cath Pci Registry, Marc Sintek, Edward Coverstone, Richard Bach, Alan Zajarias, John Lasala, Howard Kurz, Kevin Kennedy, Jasvindar Singh

2020-Current year OA Pubs

[Figure: see text].


Enabling Qualitative Research Data Sharing Using A Natural Language Processing Pipeline For Deidentification: Moving Beyond Hipaa Safe Harbor Identifiers, Aditi Gupta, Albert Lai, Jessica Mozersky, Xiaoteng Ma, Heidi Walsh, James M Dubois Jul 2021

Enabling Qualitative Research Data Sharing Using A Natural Language Processing Pipeline For Deidentification: Moving Beyond Hipaa Safe Harbor Identifiers, Aditi Gupta, Albert Lai, Jessica Mozersky, Xiaoteng Ma, Heidi Walsh, James M Dubois

2020-Current year OA Pubs

OBJECTIVE: Sharing health research data is essential for accelerating the translation of research into actionable knowledge that can impact health care services and outcomes. Qualitative health research data are rarely shared due to the challenge of deidentifying text and the potential risks of participant reidentification. Here, we establish and evaluate a framework for deidentifying qualitative research data using automated computational techniques including removal of identifiers that are not considered HIPAA Safe Harbor (HSH) identifiers but are likely to be found in unstructured qualitative data.

MATERIALS AND METHODS: We developed and validated a pipeline for deidentifying qualitative research data using automated …


Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al. Jul 2021

Oral Once-Daily Berotralstat For The Prevention Of Hereditary Angioedema Attacks: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial, Bruce Zuraw, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 …


The New (Version 9) American Joint Committee On Cancer Tumor, Node, Metastasis Staging For Cervical Cancer, Alexander B Olawaiye, Thomas P Baker, M Kay Washington, David G Mutch Jul 2021

The New (Version 9) American Joint Committee On Cancer Tumor, Node, Metastasis Staging For Cervical Cancer, Alexander B Olawaiye, Thomas P Baker, M Kay Washington, David G Mutch

2020-Current year OA Pubs

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is …


Sonothermogenetics For Noninvasive And Cell-Type Specific Deep Brain Neuromodulation, Yaoheng Yang, Christopher Pham Pacia, Dezhuang Ye, Lifei Zhu, Hongchae Baek, Yimei Yue, Jinyun Yuan, Mark J Miller, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen Jul 2021

Sonothermogenetics For Noninvasive And Cell-Type Specific Deep Brain Neuromodulation, Yaoheng Yang, Christopher Pham Pacia, Dezhuang Ye, Lifei Zhu, Hongchae Baek, Yimei Yue, Jinyun Yuan, Mark J Miller, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain.

OBJECTIVE: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect.

METHODS: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon calcium imaging. Behavioral response evoked by sonothermogenetic …


Deteriorated Regional Calf Microcirculation Measured By Contrast-Free Mri In Patients With Diabetes Mellitus And Relation With Physical Activity, Jie Zheng, Christopher Sorensen, Ran Li, Hongyu An, Charles F Hildebolt, Mohamed A Zayed, Michael J Mueller, Mary K Hastings Jul 2021

Deteriorated Regional Calf Microcirculation Measured By Contrast-Free Mri In Patients With Diabetes Mellitus And Relation With Physical Activity, Jie Zheng, Christopher Sorensen, Ran Li, Hongyu An, Charles F Hildebolt, Mohamed A Zayed, Michael J Mueller, Mary K Hastings

2020-Current year OA Pubs

OBJECTIVE: To evaluate regional calf muscle microcirculation in people with diabetes mellitus (DM) with and without foot ulcers, compared to healthy control people without DM, using contrast-free magnetic resonance imaging methods.

METHODS: Three groups of subjects were recruited: non-DM controls, DM, and DM with foot ulcers (DM + ulcer), all with ankle brachial index (ABI) > 0.9. Skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in calf muscle were measured at rest and during a 5-min isometric ankle plantarflexion exercise. Subjects completed the Yale physical activity survey.

RESULTS: The exercise SMBF (ml/min/100 g) of the medial gastrocnemius muscle were …


Machine Learning For Modeling The Progression Of Alzheimer Disease Dementia Using Clinical Data: A Systematic Literature Review, Sayantan Kumar, Inez Oh, Suzanne Schindler, Albert M Lai, Philip R O Payne, Aditi Gupta Jul 2021

Machine Learning For Modeling The Progression Of Alzheimer Disease Dementia Using Clinical Data: A Systematic Literature Review, Sayantan Kumar, Inez Oh, Suzanne Schindler, Albert M Lai, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

OBJECTIVE: Alzheimer disease (AD) is the most common cause of dementia, a syndrome characterized by cognitive impairment severe enough to interfere with activities of daily life. We aimed to conduct a systematic literature review (SLR) of studies that applied machine learning (ML) methods to clinical data derived from electronic health records in order to model risk for progression of AD dementia.

MATERIALS AND METHODS: We searched for articles published between January 1, 2010, and May 31, 2020, in PubMed, Scopus, ScienceDirect, IEEE Explore Digital Library, Association for Computing Machinery Digital Library, and arXiv. We used predefined criteria to select relevant …


Comparison Of Early Warning Scores For Sepsis Early Identification And Prediction In The General Ward Setting, Sean C Yu, Nirmala Shivakumar, Kevin Betthauser, Aditi Gupta, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson Jul 2021

Comparison Of Early Warning Scores For Sepsis Early Identification And Prediction In The General Ward Setting, Sean C Yu, Nirmala Shivakumar, Kevin Betthauser, Aditi Gupta, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance (area under the receiver operating characteristic curve: 0.803 [95% confidence interval [CI]: …


Renal Mucosa-Associated Lymphoid Tissue (Malt) Associated End-Stage Renal Disease In A Patient Presenting With Diarrhea, Faran S. Polani, Fawwad Zaidi Jul 2021

Renal Mucosa-Associated Lymphoid Tissue (Malt) Associated End-Stage Renal Disease In A Patient Presenting With Diarrhea, Faran S. Polani, Fawwad Zaidi

2020-Current year OA Pubs

Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) is most commonly found in the GI tract. Other less common anatomical sites for MALT include the skin, intestine, salivary glands, lungs, and ocular adnexa. Isolated MALT of the kidney has only been sporadically reported. Most of the reported cases in the literature present with underlying renal mass and are generally diagnosed post nephrectomy. We present a case of a 73-year-old gentleman with biopsy-proven primary MALT of the kidney who presented with acute kidney injury (AKI) in the background of


Results From 2 Cohort Studies In Central Africa Show That Clearance Of Wuchereria Bancrofti Infection After Repeated Rounds Of Mass Drug Administration With Albendazole Alone Is Closely Linked To Individual Adherence, Jérémy T Campillo, Naomi P Awaca-Uvon, Francois Missamou, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Gary J Weil, Frédéric Louya, Michel Boussinesq, Sébastien D S Pion, Cédric B Chesnais Jul 2021

Results From 2 Cohort Studies In Central Africa Show That Clearance Of Wuchereria Bancrofti Infection After Repeated Rounds Of Mass Drug Administration With Albendazole Alone Is Closely Linked To Individual Adherence, Jérémy T Campillo, Naomi P Awaca-Uvon, Francois Missamou, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Gary J Weil, Frédéric Louya, Michel Boussinesq, Sébastien D S Pion, Cédric B Chesnais

2020-Current year OA Pubs

BACKGROUND: Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semiannual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high interindividual heterogeneity in the clearance of infection was observed.

METHODS: We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then …


Mechanisms Underlying Disorders Of Consciousness: Bridging Gaps To Move Toward An Integrated Translational Science, Andrea I Luppi, Joshua Cain, Lennart R B Spindler, Urszula J Górska, Daniel Toker, Andrew E Hudson, Emery N Brown, Michael N Diringer, Robert D Stevens, Marcello Massimini, Martin M Monti, Emmanuel A Stamatakis, Melanie Boly, Curing Coma Campaign And Its Contributing Collaborators Jul 2021

Mechanisms Underlying Disorders Of Consciousness: Bridging Gaps To Move Toward An Integrated Translational Science, Andrea I Luppi, Joshua Cain, Lennart R B Spindler, Urszula J Górska, Daniel Toker, Andrew E Hudson, Emery N Brown, Michael N Diringer, Robert D Stevens, Marcello Massimini, Martin M Monti, Emmanuel A Stamatakis, Melanie Boly, Curing Coma Campaign And Its Contributing Collaborators

2020-Current year OA Pubs

AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders.

METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them.

RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral …


Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al. Jul 2021

Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ

RESULTS: Of 504 patients, mRCC …


Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al. Jul 2021

Cystic Fibrosis Foundation Consensus Statements For The Care Of Cystic Fibrosis Lung Transplant Recipients, Pali Shah, Marina Litvin, Ramsey R Hachem, Et Al.

2020-Current year OA Pubs

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed …


Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert Jul 2021

Bintrafusp Alfa, A Bifunctional Fusion Protein Targeting Tgf-Β And Pd-L1, In Patients With Esophageal Adenocarcinoma: Results From A Phase 1 Cohort, Benjamin Tan, Adnan Khattak, Enriqueta Felip, Karen Kelly, Patricia Rich, Ding Wang, Christoph Helwig, Isabelle Dussault, Laureen S Ojalvo, Nicolas Isambert

2020-Current year OA Pubs

BACKGROUND: Esophageal adenocarcinoma patients have limited treatment options. TGF-β can be upregulated in esophageal adenocarcinoma, and blocking this pathway may enhance clinical response to PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of bintrafusp alfa in patients with advanced, post-platinum esophageal adenocarcinoma, unselected for PD-L1 expression.

PATIENTS AND METHODS: In this phase 1 study, patients with post-platinum, PD-L1-unselected esophageal adenocarcinoma received bintrafusp alfa 1200 mg …


Cost Talk: Protocol For A Stepped-Wedge Cluster Randomized Trial Of An Intervention Helping Patients And Urologic Surgeons Discuss Costs Of Care For Slow-Growing Prostate Cancer During Shared Decision-Making, Mary C Politi, Rachel C Forcino, Katelyn Parrish, Marie-Anne Durand, A James O'Malley, Glyn Elwyn Jun 2021

Cost Talk: Protocol For A Stepped-Wedge Cluster Randomized Trial Of An Intervention Helping Patients And Urologic Surgeons Discuss Costs Of Care For Slow-Growing Prostate Cancer During Shared Decision-Making, Mary C Politi, Rachel C Forcino, Katelyn Parrish, Marie-Anne Durand, A James O'Malley, Glyn Elwyn

2020-Current year OA Pubs

BACKGROUND: Costs of care are important to patients making cancer treatment decisions, but clinicians often do not feel prepared to discuss treatment costs. We aim to (1) assess the impact of a conversation-based decision aid (Option Grid) containing cost information about slow-growing prostate cancer management options, combined with urologic surgeon training, on the frequency and quality of patient-urologic surgeon cost conversations, and (2) examine the impact of the decision aid and surgeon training on decision quality.

METHODS: We will conduct a stepped-wedge cluster randomized trial in outpatient urology practices affiliated with a large academic medical center in the USA. We …


A Systematic Review Of School Health Policy Measurement Tools: Implementation Determinants And Outcomes, Gabriella M Mcloughlin, Peg Allen, Callie Walsh-Bailey, Ross C Brownson Jun 2021

A Systematic Review Of School Health Policy Measurement Tools: Implementation Determinants And Outcomes, Gabriella M Mcloughlin, Peg Allen, Callie Walsh-Bailey, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Governments in some countries or states/provinces mandate school-based policies intended to improve the health and well-being of primary and secondary students and in some cases the health of school staff. Examples include mandating a minimum time spent per week in programmed physical activity, mandating provision of healthy foods and limiting fat content of school meals, and banning tobacco products or use on school campuses. Although school health researchers have studied whether schools, districts, or states/provinces are meeting requirements, it is unclear to what extent implementation processes and determinants are assessed. The purposes of the present systematic review of quantitative …


Directed Evolution Of An Enhanced Pou Reprogramming Factor For Cell Fate Engineering, Daisylyn Senna Tan, Gary D Stormo, Et Al. Jun 2021

Directed Evolution Of An Enhanced Pou Reprogramming Factor For Cell Fate Engineering, Daisylyn Senna Tan, Gary D Stormo, Et Al.

2020-Current year OA Pubs

Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, and maturity for widespread adoption and clinical translation. Here, we used Oct4, Sox2, Klf4, and c-Myc driven pluripotency reprogramming to evaluate methods for enhancing and tailoring cell fate transitions, through directed evolution with iterative screening of pooled mutant libraries and phenotypic selection. We identified an artificially evolved and enhanced POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency. In contrast to Oct4, not only can ePOU induce pluripotency with Sox2 alone, but it can also do so in the …


Advanced Cognitive Impairment Among Older Nursing Home Residents, Tadeja Gracner, Patricia W Stone, Mansi Agarwal, Mark Sorbero, Susan L Mitchell, Andrew W Dick Jun 2021

Advanced Cognitive Impairment Among Older Nursing Home Residents, Tadeja Gracner, Patricia W Stone, Mansi Agarwal, Mark Sorbero, Susan L Mitchell, Andrew W Dick

2020-Current year OA Pubs

BACKGROUND: Though work has been done studying nursing home (NH) residents with either advanced Alzheimer's disease (AD) or Alzheimer's disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD.

METHODS: This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011-2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe …


A Case Of Intermittent Left Bundle Branch Block, Syed M. Saad, Faran S. Polani, Paul Lelorier Jun 2021

A Case Of Intermittent Left Bundle Branch Block, Syed M. Saad, Faran S. Polani, Paul Lelorier

2020-Current year OA Pubs

An 82-year-old woman with uncontrolled hypertension and occasional exertional dyspnea was found to be in intermittent left bundle branch block (LBBB). Her laboratory results, echocardiogram, and ischemic workup were unremarkable. This case highlights that intermittent LBBB is not always associated with coronary ischemia, vasospasm, blunt cardiac injury, drugs, and high catecholaminergic or inflammatory states.


Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al. Jun 2021

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

METHODS: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of …


The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al. Jun 2021

The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al.

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma …


Gps Driving: A Digital Biomarker For Preclinical Alzheimer Disease, Sayeh Bayat, Ganesh M Babulal, Suzanne E Schindler, Anne M Fagan, John C Morris, Alex Mihailidis, Catherine M Roe Jun 2021

Gps Driving: A Digital Biomarker For Preclinical Alzheimer Disease, Sayeh Bayat, Ganesh M Babulal, Suzanne E Schindler, Anne M Fagan, John C Morris, Alex Mihailidis, Catherine M Roe

2020-Current year OA Pubs

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. Preclinical AD is the period during which early AD brain changes are present but cognitive symptoms have not yet manifest. The presence of AD brain changes can be ascertained by molecular biomarkers obtained via imaging and lumbar puncture. However, the use of these methods is limited by cost, acceptability, and availability. The preclinical stage of AD may have a subtle functional signature, which can impact complex behaviours such as driving. The objective of the present study was to evaluate the ability of in-vehicle GPS data loggers to distinguish cognitively …


Inferring Tf Activities And Activity Regulators From Gene Expression Data With Constraints From Tf Perturbation Data, Cynthia Z Ma, Michael R Brent Jun 2021

Inferring Tf Activities And Activity Regulators From Gene Expression Data With Constraints From Tf Perturbation Data, Cynthia Z Ma, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: The activity of a transcription factor (TF) in a sample of cells is the extent to which it is exerting its regulatory potential. Many methods of inferring TF activity from gene expression data have been described, but due to the lack of appropriate large-scale datasets, systematic and objective validation has not been possible until now.

RESULTS: We systematically evaluate and optimize the approach to TF activity inference in which a gene expression matrix is factored into a condition-independent matrix of control strengths and a condition-dependent matrix of TF activity levels. We find that expression data in which the activities …


A Strong Effect Of Individual Compliance With Mass Drug Administration For Lymphatic Filariasis On Sustained Clearance Of Soil-Transmitted Helminth Infections, Jérémy T Campillo, Naomi P Awaca-Uvon, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Johnny Vlaminck, Gary J Weil, Michel Boussinesq, Cédric B Chesnais, Sébastien D S Pion Jun 2021

A Strong Effect Of Individual Compliance With Mass Drug Administration For Lymphatic Filariasis On Sustained Clearance Of Soil-Transmitted Helminth Infections, Jérémy T Campillo, Naomi P Awaca-Uvon, Jean-Paul Tambwe, Godefroy Kuyangisa-Simuna, Johnny Vlaminck, Gary J Weil, Michel Boussinesq, Cédric B Chesnais, Sébastien D S Pion

2020-Current year OA Pubs

BACKGROUND: The impact of semiannual mass drug administration (MDA) with albendazole (ALB; 400 mg) alone on lymphatic filariasis (LF) and soil-transmitted helminth (STH) infections was assessed during two trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of Congo. The collected data were analyzed to evaluate the effect of compliance with ALB treatment on STH infections.

METHODS: STH infections were diagnosed with duplicate Kato-Katz thick smears and the results are reported as eggs per gram of stool. All subjects with at least two STH infection assessments were included in the analyses. We used parametric …


Teaching Scripts Via Smartphone App Facilitate Resident-Led Teaching Of Medical Students, Nicholas R Zessis, Amanda R Dube, Arhanti Sadanand, Jordan J Cole, Christine M Hrach, Yasmeen N Daud Jun 2021

Teaching Scripts Via Smartphone App Facilitate Resident-Led Teaching Of Medical Students, Nicholas R Zessis, Amanda R Dube, Arhanti Sadanand, Jordan J Cole, Christine M Hrach, Yasmeen N Daud

2020-Current year OA Pubs

BACKGROUND: Previous studies have suggested that resident physicians are the most meaningful teachers during the clinical clerkships of third-year medical students (MS3s). Unfortunately, residents often feel unprepared for this crucial role. The pediatrics clerkship at our institution identified a paucity in the frequency of resident-led teaching with MS3s. Lack of confidence, suboptimal teaching space, and insufficient time were cited as the most significant barriers. To enhance resident-led teaching of MS3s, we created teaching scripts of general pediatrics topics accessible via a smartphone application (app).

METHODS: Prior to the implementation of the app, MS3s and pediatric residents were surveyed on clerkship …


Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al Jun 2021

Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al

2020-Current year OA Pubs

BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus …


Destination Shapes Antibiotic Resistance Gene Acquisitions, Abundance Increases, And Diversity Changes In Dutch Travelers, Alaric W D'Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M Van Hattem, Maris S Arcilla, Damian C Melles, Menno D De Jong, Constance Schultsz, Combat Consortium, Gautam Dantas, John Penders Jun 2021

Destination Shapes Antibiotic Resistance Gene Acquisitions, Abundance Increases, And Diversity Changes In Dutch Travelers, Alaric W D'Souza, Manish Boolchandani, Sanket Patel, Gianluca Galazzo, Jarne M Van Hattem, Maris S Arcilla, Damian C Melles, Menno D De Jong, Constance Schultsz, Combat Consortium, Gautam Dantas, John Penders

2020-Current year OA Pubs

BACKGROUND: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel's effects on the gut resistome remain largely unknown.

METHODS: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of …