Medicine and Health Sciences Commons^™

Persistence Of Onchocerciasis In Villages In Enugu And Ogun States In Nigeria Following Many Rounds Of Mass Distribution Of Ivermectin, Uwem F Ekpo, Obiora A Eneanya, Edith N Nwankwo, Islamiat Y Soneye, Gary J Weil, Peter U Fischer, Obioma C Nwaorgu

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis is endemic in most local government areas (LGAs) in Enugu and Ogun states. Most meso- and hyper-endemic LGAs have received many rounds of ivermectin mass drug administration (MDA). This study aimed to determine the current prevalence of onchocerciasis in villages in Enugu and Ogun states that were formerly highly endemic and to assess progress toward elimination of the infection in areas believed to be at high risk for persistence.

METHODS: Cross-sectional community surveys were conducted 8 to 12 months after the last round of MDA in 16 villages (6 in Enugu state and 10 in Ogun state) in …

Fdg-Pet/Mri For Nonoperative Management Of Rectal Cancer: A Prospective Pilot Study, Semra Ince, Malak Itani, Lauren E Henke, Radhika K Smith, Paul E Wise, Matthew G Mutch, Sean C Glasgow, Matthew L Silviera, Katrina S Pedersen, Steven R Hunt, Hyun Kim, Tyler J Fraum

2020-Current year OA Pubs

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted …

An Allosteric Modulator Activates Bk Channels By Perturbing Coupling Between Ca2+ Binding And Pore Opening, Guohui Zhang, Xianjin Xu, Zhiguang Jia, Yanyan Geng, Hongwu Liang, Jingyi Shi, Martina Marras, Carlota Abella, Karl L Magleby, Jonathan R Silva, Jianhan Chen, Xiaoqin Zou, Jianmin Cui

2020-Current year OA Pubs

BK type Ca

A Human Stat3 Gain-Of-Function Variant Confers T Cell Dysregulation Without Predominant Treg Dysfunction In Mice, Erica G Schmitt, Kelsey A Toth, Samuel I Risma, Ana Kolicheski, Nermina Saucier, Rafael J. Feliciano Berríos, Zev J. Greenberg, Jennifer W. Leiding, Jack J. Bleesing, Akaluck Thatayatikom, Laura G. Schuettpelz, John R. Edwards, Tiphanie P. Vogel, Megan A Cooper

2020-Current year OA Pubs

Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease. However, the mechanisms of disease pathogenesis in STAT3 GOF syndrome remain largely unknown, and treatment is challenging. We developed a knock-in mouse model harboring a de novo pathogenic human STAT3 variant (p.G421R) …

Tuft-Cell-Intrinsic And -Extrinsic Mediators Of Norovirus Tropism Regulate Viral Immunity, Madison S Strine, Mia Madel Alfajaro, Vincent R Graziano, Jaewon Song, Leon L Hsieh, Ryan Hill, Jun Guo, Kelli L Vandussen, Robert C Orchard, Megan T Baldridge, Sanghyun Lee, Craig B Wilen

2020-Current year OA Pubs

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoV

Ornithine Decarboxylase Supports Ilc3 Responses In Infectious And Autoimmune Colitis Through Positive Regulation Of Il-22 Transcription, Vincent Peng, Siyan Cao, Tihana Trsan, Jennifer K Bando, Julian Avila-Pacheco, John L Cleveland, Clary Clish, Ramnik J Xavier, Marco Colonna

2020-Current year OA Pubs

Group 3 innate lymphoid cells (ILC3s) are RORγT

The Evolution, Current Indications And Outcomes Of Cementless Total Knee Arthroplasty, Maria T Schwabe, Charles P Hannon

2020-Current year OA Pubs

Total knee arthroplasty (TKA) has been performed by orthopedic surgeons for decades, but the cementless TKA has only recently gained much interest in the world of arthroplasty. Initially, early designs had multiple complications, particularly with aseptic loosening due to osteolysis and micromotion. However, modifications have shown good outcomes and excellent survivorship. Over the last several decades, changes in implant designs as well as implant materials/coatings have helped with bone in growth and stability. Furthermore, surgeons have been performing TKA in younger and more obese patients as these populations have been increasing. Good results from the cementless TKA compared to cemented …

Combination Of Common Mtdna Variants Results In Mitochondrial Dysfunction And A Connective Tissue Dysregulation, Patrick M Schaefer, Benjamin A Garcia, Et Al.

2020-Current year OA Pubs

Mitochondrial dysfunction can be associated with a range of clinical manifestations. Here, we report a family with a complex phenotype including combinations of connective tissue, neurological, and metabolic symptoms that were passed on to all surviving children. Analysis of the maternally inherited mtDNA revealed a novel genotype encompassing the haplogroup J - defining mitochondrial DNA (mtDNA)

Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes As Antecedents To Reward Deficiency Syndrome (Rds) Hypodopaminergia's Effect On Addictive And Non-Addictive Behaviors In A Nuclear Family, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Panayotis K Thanos, Igor Elman, Mauro Ceccanti, Rajendra D Badgaiyan, Thomas Mclaughlin, Ashim Gupta, Anish Bajaj, David Baron, B William Downs, Debasis Bagchi, Mark S Gold

2020-Current year OA Pubs

This case series presents the novel genetic addiction risk score (GARS), which shows a high prevalence of polymorphic risk alleles of reward genes in a nuclear family with multiple reward deficiency syndrome (RDS) behavioral issues expressing a hypodopaminergic antecedent. The family consists of a mother, father, son, and daughter. The mother experienced issues with focus, memory, anger, and amotivational syndrome. The father experienced weight issues and depression. The son experienced heavy drinking, along with some drug abuse and anxiety. The daughter experienced depression, lethargy, brain fog, focus issues, and anxiety, among others. A major clinical outcome of the results presented …

High-Throughput Analysis Of Tissue Microarrays Using Automated Desorption Electrospray Ionization Mass Spectrometry, Nicolás M Morato, Hannah Marie Brown, Diogo Garcia, Erik H Middlebrooks, Mark Jentoft, Kaisorn Chaichana, Alfredo Quiñones-Hinojosa, R Graham Cooks

2020-Current year OA Pubs

Tissue microarrays (TMAs) are commonly used for the rapid analysis of large numbers of tissue samples, often in morphological assessments but increasingly in spectroscopic analysis, where specific molecular markers are targeted via immunostaining. Here we report the use of an automated high-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS) for the rapid generation and online analysis of high-density (6144 samples/array) TMAs, at rates better than 1 sample/second. Direct open-air analysis of tissue samples (hundreds of nanograms) not subjected to prior preparation, plus the ability to provide molecular characterization by tandem mass spectrometry (MS/MS), make this experiment versatile …

Socioeconomic Status And Modification Of Atherosclerotic Cardiovascular Disease Risk Prediction: Epidemiological Analysis Using Data From The Atherosclerosis Risk In Communities Study, Kamal Henderson, Brystana Kaufman, Jason S. Rotter, Sally Stearns, Carla A A Sueta, Randi Foraker, P Michael Ho, Patricia P Chang

2020-Current year OA Pubs

OBJECTIVE: Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES).

DESIGN: Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups.

SETTING: Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland.

PARTICIPANTS: We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998).

PRIMARY OUTCOME MEASURES: Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES …

Oxidative Stress-Induced Cellular Senescence In Aging Retina And Age-Related Macular Degeneration, Ryo Terao, Tazbir Ahmed, Ayana Suzumura, Hiroko Terasaki

2020-Current year OA Pubs

Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, …

Single-Cell Multiomics Identifies Clinically Relevant Mesenchymal Stem-Like Cells And Key Regulators For Mpnst Malignancy, Lai Man Natalie Wu, Joshua Rubin, Et Al.

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumor (MPNST), a highly aggressive Schwann cell (SC)-derived soft tissue sarcoma, arises from benign neurofibroma (NF); however, the identity, heterogeneity and origins of tumor populations remain elusive. Nestin

Preventive Behaviors And Information Sources During Covid-19 Pandemic: A Cross-Sectional Study In Japan, Manae Uchibori, Cyrus Ghaznavi, Michio Murakami, Akifumi Eguchi, Hiroyuki Kunishima, Satoshi Kaneko, Keiko Maruyama-Sakurai, Hiroaki Miyata, Shuhei Nomura

2020-Current year OA Pubs

BACKGROUND: individual preventive behaviors are one of the key measures needed to prevent the spread of COVID-19. This study sought to identify the factors associated with the adoption of COVID-19 preventive measures, focusing specifically on information sources.

METHODS: we conducted a nationally representative cross-sectional survey of 30,053 Japanese adults in February 2021. The survey asked about socioeconomic, health-related, and psychological characteristics, attitudes toward immunization, and the use of information sources regarding COVID-19. We have constructed multivariable logistic regression to estimate the factors associated with the adoption of three preventive measures: 3Cs avoidance, hand hygiene and respiratory hygiene.

RESULTS: socioeconomic variables, …

Bi-Allelic Camsap1 Variants Cause A Clinically Recognizable Neuronal Migration Disorder, Reham Khalaf-Nazzal, Jennifer L Griffith, Joseph R Walsh, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T Curiel, Et Al.

2020-Current year OA Pubs

Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and …

Phenome-Wide Analysis Of Taiwan Biobank Reveals Novel Glycemia-Related Loci And Genetic Risks For Diabetes, Chia-Jung Lee, Ting-Huei Chen, Aylwin Ming Wee Lim, Chien-Ching Chang, Jia-Jyun Sie, Pei-Lung Chen, Su-Wei Chang, Shang-Jung Wu, Chia-Lin Hsu, Ai-Ru Hsieh, Wei-Shiung Yang, Cathy S J Fann

2020-Current year OA Pubs

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA

Phase Iii Trial Of Chemoradiotherapy With Temozolomide Plus Nivolumab Or Placebo For Newly Diagnosed Glioblastoma With Methylated Mgmt Promoter, Michael Lim, George Ansstas, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).

METHODS: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days …

Proteogenomic Markers Of Chemotherapy Resistance And Response In Triple-Negative Breast Cancer, Meenakshi Anurag, Shunqiang Li, Ian S Hagemann, Jeremy Hoog, Foluso O Ademuyiwa, Et Al.

2020-Current year OA Pubs

UNLABELLED: Microscaled proteogenomics was deployed to probe the molecular basis for differential response to neoadjuvant carboplatin and docetaxel combination chemotherapy for triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, and fatty acid metabolism, that were associated with resistance. Both proteomics and transcriptomics revealed that sensitivity was marked by elevation of DNA repair, E2F targets, G2-M checkpoint, interferon-gamma signaling, and immune-checkpoint components. Proteogenomic analyses of somatic copy-number aberrations identified a resistance-associated 19q13.31-33 deletion where LIG1, POLD1, and XRCC1 are located. In orthogonal datasets, LIG1 (DNA ligase I) gene deletion and/or low …

The 5-Hydroxymethylcytosine Landscape Of Prostate Cancer, Martin Sjöström, Nupam P Mahajan, Christopher A Maher, Et Al.

2020-Current year OA Pubs

UNLABELLED: Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, …

Real-World Utilization And Outcomes Of Systemic Therapy Among Patients With Advanced Or Recurrent Endometrial Cancer In The United States, Jinan Liu, Bruno Emond, Eric M Maiese, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean A Hurteau, Premal H Thaker

2020-Current year OA Pubs

OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States.

METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line …

Ascertainment Of Vaccination Status By Self-Report Versus Source Documentation: Impact On Measuring Covid-19 Vaccine Effectiveness, Meagan Stephenson, Jennie H Kwon, Et Al

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates.

METHODS: Hospitalized adults (≥18 years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement …

Sars-Cov-2 Mrna Vaccination Causes Prolonged Increased Cortical Thickening And Vascularity In Ipsilateral Axillary Lymph Nodes, Sharlene A Teefey, William D Middleton, Jackson S Turner, Ali H Ellebedy, Teresa Suessen, Michael Wallendorf, Jane A O'Halloran, Rachel Presti

2020-Current year OA Pubs

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks.

METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. …

Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al.

2020-Current year OA Pubs

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [

N-Terminal Acetylation And Arginylation Of Actin Determines The Architecture And Assembly Rate Of Linear And Branched Actin Networks, Samantha M Chin, Tomoyuki Hatano, Lavanya Sivashanmugam, Andrejus Suchenko, Anna S Kashina, Mohan K Balasubramanian, Silvia Jansen

2020-Current year OA Pubs

The great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes, including cell migration, endocytosis, and cell division. While it is known that this versatility is the result of the many actin-remodeling activities of actin-binding proteins, such as Arp2/3 and cofilin, recent work also implicates posttranslational acetylation or arginylation of the actin N terminus itself as an equally important regulatory mechanism. However, the molecular mechanisms by which acetylation and arginylation alter the properties of actin are not well understood. Here, we directly compare how processing and modification of the N terminus of actin …

An Assessment Of Pediatric Residency Applicant Perceptions Of "Fit" During The Virtual Interview Era, Jason D. Vadhan, Jorge G. Zarate Rodriguez, Michael Wallendorf, Michael M. Awad, Andrew J. White

2020-Current year OA Pubs

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants' ability to discern "fit" to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants' ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs.

METHODS: An online, anonymous survey was …

Pembrolizumab For Patients With Non-Hodgkin Lymphoma: Phase 1b Keynote-013 Study, John Kuruvilla, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

The multicohort phase 1b KEYNOTE-013 study (NCT01953692) evaluated the safety and efficacy of pembrolizumab in patients with relapsed or refractory NHL who were ineligible for or failed hematopoietic cell transplantation (HCT). Patients received pembrolizumab (cohort 4) or pembrolizumab plus lenalidomide (cohort 5). Primary end points were safety and objective response rate (ORR) per IWG 2007 criteria. Cohort 4 included 89 patients. ORR was 22% (19/86; 90% CI 15-31; 10 CR, nine PR); ORRs by disease type were 48% (10/21), 10% (2/20), 12% (5/41), and 50% (2/4), for PMBCL, FL, DLBCL, and 'other' NHL, respectively. Toxicity was as predicted. Cohort 5 …

Risk-Adjusted Safety Analysis Of The Oral Jak2/Irak1 Inhibitor Pacritinib In Patients With Myelofibrosis, Naveen Pemmaraju, Claire Harrison, Vikas Gupta, Srdan Verstovsek, Bart Scott, Stephen T Oh, Francesca Palandri, Haifa Kathrin Al-Ali, Marta Sobas, Mary Frances Mcmullin, Ruben Mesa, Sarah Buckley, Karisse Roman-Torres, Alessandro Vannucchi, Abdulraheem Yacoub

2020-Current year OA Pubs

The safety profile of the novel oral JAK2/IRAK1 inhibitor pacritinib in patients with cytopenic myelofibrosis was described in the Phase 2 PAC203 and Phase 3 PERSIST-2 studies. To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia.

Age-Dependent Rebound In Asthma Exacerbations After Covid-19 Lockdown, Guy Hazan, Carolyn Fox, Huram Mok, Jeffrey Haspel

2020-Current year OA Pubs

BACKGROUND: Virus mitigation measures enacted early in the coronavirus infectious disease 2019 (COVID-19) pandemic suppressed common respiratory viruses and reduced the number of obstructive lung disease exacerbations. However, many localities began to ease these precautions in the year 2021, leading to a resurgence of non-COVID viruses. How asthma and chronic obstructive pulmonary disease (COPD) activity responded to this upswing in viral abundance is unclear.

OBJECTIVE: Our aim was to examine how viral resurgence during the relaxation of COVID-19 restrictions affected asthma and COPD exacerbations.

METHODS: We analyzed electronic medical records for emergency department (ED) respiratory virus positivity, asthma visits, and …

Durable Melanoma Control Following Disseminated Talimogene Laherparepvec Herpetic Infection, Leonid Shmuylovich, Aubriana M Mcevoy, Ryan C Fields, Leonel Hernandez-Aya, George Ansstas, David Y Chen

2020-Current year OA Pubs

No abstract provided.

Acute-Onset, Painful, Acral Granuloma Annulare In A 52-Year-Old Female, Faisal S Ahmad, Michael R Vittori, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.