Digital Commons Network^™

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

The Relationship Between Dark Triad Personality Traits And Sexting Behaviors Among Adolescents And Young Adults Across 11 Countries., Mara Morelli, Flavio Urbini, Dora Bianchi, Roberto Baiocco, Elena Cattelino, Fiorenzo Laghi, Piotr Sorokowski, Michal Misiak, Martyna Dziekan, Heather Hudson, Alexandra Marshall, Thanh Truc T Nguyen, Lauren Mark, Kamil Kopecky, René Szotkowski, Ezgi Toplu Demirtaş, Joris Van Ouytsel, Koen Ponnet, Michel Walrave, Tingshao Zhu, Ya Chen, Nan Zhao, Xiaoqian Liu, Alexander Voiskounsky, Nataliya Bogacheva, Maria Ioannou, John Synnott, Kalliopi Tzani-Pepelasi, Vimala Balakrishnan, Moses Okumu, Eusebius Small, Silviya Pavlova Nikolova, Michelle Drouin, Antonio Chirumbolo

Health Services and Informatics Research

BACKGROUND: Sexting is an increasingly common phenomenon among adolescents and young adults. Some studies have investigated the role of personality traits in different sexting behaviors within mainstream personality taxonomies like Big Five and HEXACO. However, very few studies have investigated the role of maladaptive personality factors in sexting. Therefore, the present study investigated the relationship between Dark Triad Personality Traits and experimental (i.e., sharing own sexts), risky (i.e., sexting under substance use and with strangers), and aggravated sexting (i.e., non-consensual sexting and sexting under pressure) across 11 countries.

METHODS: An online survey was completed by 6093 participants (Mage = 20.35; …

Lawmakers' Use Of Scientific Evidence Can Be Improved, D Max Crowley, J Taylor Scott, Elizabeth C Long, Lawrie Green, Azaliah Israel, Lauren Supplee, Elizabeth Jordan, Kathryn Oliver, Shannon Guillot-Wright, Brittany Gay, Rachel Storace, Naomi Torres-Mackie, Yolanda Murphy, Sandra Donnay, Jenna Reardanz, Rebecca Smith, Kristina Mcguire, Elizabeth Baker, Ana Antonopoulos, Mary Mccauley, Cagla Giray

Faculty, Staff and Student Publications

Core to the goal of scientific exploration is the opportunity to guide future decision-making. Yet, elected officials often miss opportunities to use science in their policymaking. This work reports on an experiment with the US Congress-evaluating the effects of a randomized, dual-population (i.e., researchers and congressional offices) outreach model for supporting legislative use of research evidence regarding child and family policy issues. In this experiment, we found that congressional offices randomized to the intervention reported greater value of research for understanding issues than the control group following implementation. More research use was also observed in legislation introduced by the intervention …

Estimation And Comparison Of Current And Future Racial/Ethnic Representation In The Us Health Care Workforce., Edward Salsberg, Chelsea Richwine, Sara Westergaard, Maria Portela Martinez, Toyese Oyeyemi, Anushree Vichare, Candice P. Chen

Fitzhugh Mullan Institute for Health Workforce Equity

No abstract provided.

The Association Between Overnight Fasting And Body Mass Index In Older Adults: The Interaction Between Duration And Timing, Qian Xiao, Cici Bauer, Tracy Layne, Mary Playdon

Faculty, Staff and Student Publications

BACKGROUND: Circadian rhythms play an important role in the regulation of eating and fasting, and mistimed dietary intakes may be detrimental to metabolic health. Extended overnight fasting has been proposed as a strategy to better align the eating-fasting cycle with the internal circadian clock, and both observational and experimental studies have linked longer overnight fasting with lower body weight. However, it remains unclear if the timing of overnight fasting modifies the relationship between fasting duration and weight outcomes.

METHODS: The current study included 495 men and 499 women age 50-74 years. Dietary intake over 12 months was assessed by 24-h …

A Brazilian National Preparedness Survey Of Anesthesiologists During The Coronavirus Pandemic, Vinícius Caldeira Quintão, Claudia Marquez Simões, Gibran Elias Harcha Munoz, Paul Barach, Maria José Carvalho Carmona, Brazilian Network For Research On Complications In Anesthesia Branca

College of Population Health Faculty Papers

No abstract provided.

Disparities In Sleep Health And Potential Intervention Models: A Focused Review., Martha E. Billings, Robyn T. Cohen, Carol M. Baldwin, Dayna A. Johnson, Brian N. Palen, Sairam Parthasarathy, Sanjay R. Patel, Maureen Russell, Ignacio E. Tapia, Ariel A. Williamson, Sunil Sharma

Project ECHO Bibliography

Disparities in sleep health are important but underrecognized contributors to health disparities. Understanding the factors contributing to sleep heath disparities and developing effective interventions are critical to improving all aspects of heath. Sleep heath disparities are impacted by socioeconomic status, racism, discrimination, neighborhood segregation, geography, social patterns, and access to health care as well as by cultural beliefs, necessitating a cultural appropriateness component in any intervention devised for reducing sleep health disparities. Pediatric sleep disparities require innovative and urgent intervention to establish a foundation of lifelong healthy sleep. Tapping the vast potential of technology in improving sleep health access may …

Implementing Evidence-Informed Practices To Make Schools Safer And More Supportive Of Sexual And Gender Minority Youth, Daniel Shattuck, Janie L Hall, Elizabeth Dickson, Amy E Green, Mary M Ramos

Pediatrics Research and Scholarship

No abstract provided.

Fatigue And Its Association With Social Participation, Functioning, And Quality Of Life In Systemic Sclerosis, Susan L. Murphy, Anna L. Kratz, Daniel Whibley, Janet L. Poole, Dinesh Khanna

Pediatrics Research and Scholarship

OBJECTIVE: Fatigue is consistently ranked as one of the most problematic symptoms of systemic sclerosis (SSc), but the impact of fatigue on daily life is not well characterized. The purpose of this study was to examine the contribution of fatigue to deficits in social participation, functioning, and quality of life.

METHODS: Baseline data from a sample undertaking a clinical trial were utilized (n = 267). Fatigue, pain interference, depressive symptoms, physical function, and social participation were assessed by measures from the Patient-Reported Outcomes Measurement Information System. Hierarchical linear regressions were performed to determine the unique contribution of fatigue to social …

Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek

Pathology Research and Scholarship

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the …

A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon

Faculty, Staff and Students Publications

2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in …

The Crosstalk Between Cardiomyocyte Calcium And Inflammasome Signaling Pathways In Atrial Fibrillation, Xiaolei Wang, Xiaohui Chen, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most frequent arrhythmia in adults. The prevalence and incidence of AF is going to increase substantially over the next a few decades. Because AF increases the risk of stroke, heart failure, dementia, and others, it severely impacts the quality of life, morbidity and mortality. Although the pathogenesis of AF is multifaceted and complex, focal ectopic activity and reentry are considered as the fundamental proarrhythmic mechanisms underlying AF development. Over the past 2 decades, large amount of evidence points to the key role of intracellular Ca2+ dysregulation in both initiation and maintenance of AF. More recently, …

On The Application, Reporting, And Sharing Of In Silico Simulations For Genetic Studies, Kaleigh Riggs, Huann-Sheng Chen, Melissa Rotunno, Bing Li, Naoko I Simonds, Leah E Mechanic, Bo Peng

Faculty, Staff and Students Publications

In silico simulations play an indispensable role in the development and application of statistical models and methods for genetic studies. Simulation tools allow for the evaluation of methods and investigation of models in a controlled manner. With the growing popularity of evolutionary models and simulation-based statistical methods, genetic simulations have been applied to a wide variety of research disciplines such as population genetics, evolutionary genetics, genetic epidemiology, ecology, and conservation biology. In this review, we surveyed 1409 articles from five journals that publish on major application areas of genetic simulations. We identified 432 papers in which genetic simulations were used …

Adapting To Remote Library Services During Covid-19., Lydia A. Howes, Lynne Ferrell, Geoffrey S. Pettys, Adam Roloff

Articles

In response to the COVID-19 pandemic and the subsequent Stay At Home order, the Southern Illinois University Medical Library utilized new technologies and implemented new virtual service models in order to improve internal communication, and to continue providing services and resources to patrons remotely. The changes happened quickly, and the librarians faced several challenges during this time, but things went smoothly overall and there were some considerable silver linings. Several of the newly adopted technologies, service models, and virtual resource offerings proved to be extremely effective and their use will continue beyond the duration of the pandemic.

Use Of Mhealth Technology For Patient-Reported Outcomes In Community-Dwelling Adults With Acquired Brain Injuries: A Scoping Review., Shannon B Juengst, Lauren Terhorst, Andrew Nabasny, Tracey Wallace, Jennifer A. Weaver, Candice L Osborne, Suzanne Perea Burns, Brittany Wright, Pey-Shan Wen, Chung-Lin Novelle Kew, John Morris

Clinical Research and Leadership Faculty Publications

The purpose of our scoping review was to describe the current use of mHealth technology for long-term assessment of patient-reported outcomes in community-dwelling individuals with acquired brain injury (ABI). Following PRISMA guidelines, we conducted a scoping review of literature meeting these criteria: (1) civilians or military veterans, all ages; (2) self-reported or caregiver-reported outcomes assessed via mobile device in the community (not exclusively clinic/hospital); (3) published in English; (4) published in 2015-2019. We searched Ovid MEDLINE(R) < 1946 to 16 August 2019, MEDLINE InProcess, EPub, Embase, and PsycINFO databases for articles. Thirteen manuscripts representing 12 distinct studies were organized by type of ABI [traumatic brain injury (TBI) and stroke] to extract outcomes, mHealth technology used, design, and inclusion of ecological momentary assessment (EMA). Outcomes included post-concussive, depressive, and affective symptoms, fatigue, daily activities, stroke risk factors, and cognitive exertion. Overall, collecting patient-reported outcomes via mHealth was feasible and acceptable in the chronic ABI population. Studies consistently showed advantage for using EMA despite variability in EMA timing/schedules. To ensure best clinical measurement, research on post-ABI outcomes should consider EMA designs (versus single time-point assessments) that provide the best timing schedules for their respective aims and outcomes and that leverage mHealth for data collection.

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

Optimizing The Use Of Telemedicine In Oncology Care: Postpandemic Opportunities, Karen E. Knudsen, Cheryl Willman, Robert Winn

Pathology Research and Scholarship

Utilization of telehealth as part of the cancer care delivery continuum dramatically escalated in response to the COVID-19 pandemic at major cancer centers across the globe. The rapid shift toward telehealth visits for nontreatment cancer care provided immediate benefit through reducing unnecessary risk of exposure, overcoming transportation barriers faced by both patients and caregivers, and fast-tracking care transformation. As such, delineating the impact of telehealth on access, health equity, quality, and outcomes will be essential for refining the use of digital strategies and telehealth toward optimizing cancer care. Herein, experiences to date with telehealth usage for oncology care are reviewed, …

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Lessons Learned From Inadequate Implementation Planning Of Team-Based Chronic Disease Management: Implementation Evaluation., Shannon L Sibbald, Rachelle Van Asseldonk, Peiwen L Cao, Benson Law

Health Studies Publications

BACKGROUND: This study was a retrospective evaluation of an unsuccessfully implemented team-based, chronic disease management program, with an aim to understand more about implementation barriers. The program, the Chronic Disease Management Initiative (CDMI) was a new collaborative model of care for patients with COPD. It utilized customized health information and interactive tools, mainly smartphones, for ongoing disease management. The program's goal was to demonstrate that integrated team-based models of care could improve patient care, as well as reduce readmission rates and emergency department visits. The program planning for CDMI began in 2017, followed by the implementation and evaluation period in …

Integrative Oncology Education: An Emerging Competency For Oncology Providers, Safiya Karim, Rita Benn, Linda E. Carlson, Judith Fouladbakhsh, Heather Greenlee, Rick Harris, N. Lynn Henry, Shruti Jolly, Sabrina Mayhew, Lisa Spratke, Eleanor M. Walker, Bradley Zebrack, Suzanna M. Zick

Radiation Oncology Articles

A growing number of cancer patients use complementary and alternative therapies during and after conventional cancer treatment. Patients are often reluctant to discuss these therapies with their oncologist, and oncologists may have limited knowledge and confidence on how to advise patients on the appropriate use. Integrative oncology is a patient-centered, evidence-informed field that utilizes mind-body practices, lifestyle modifications and/or natural products interwoven with conventional cancer treatment. It prioritizes safety and best available evidence to offer appropriate interventions alongside conventional care. There are few opportunities for oncologists to learn about integrative oncology. In this commentary, we highlight the Integrative Oncology Scholars …

Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka

Manuscripts, Articles, Book Chapters and Other Papers

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Echo-Ct: An Interdisciplinary Videoconference Model For Identifying Potential Postdischarge Transition-Of-Care Events., Mariana R Gonzalez, Lauren Junge-Maughan, Lewis A Lipsitz, Amber Moore

Project ECHO Bibliography

BACKGROUND: Discharge from the hospital to a post-acute care setting can be complex and potentially dangerous, with opportunities for errors and lapses in communication between providers. Data collected through the Extension for Community Health Outcomes- Care Transitions (ECHO-CT) model were used to identify and classify transition-of-care events (TCEs).

METHODS: The ECHO-CT model employs multidisciplinary videoconferences between a hospital-based team and providers in post-acute care settings; during these conferences, concerns regarding the patient's care transition were identified and recorded. The videoconferences took place from January 2016 to October 2018 and included patients discharged from inpatient medical and surgical services to a …

Computer Automation For Physics Chart Check Should Be Adopted In Clinic To Replace Manual Chart Checking For Radiotherapy, Edward L. Clouser, Quan Chen, Yi Rong

Radiation Medicine Faculty Publications

No abstract provided.

Flortaucipir (Tau) Pet In Lgi1 Antibody Encephalitis, Gregory S Day, Brian A Gordon, Austin Mccullough, Robert C Bucelli, Richard J Perrin, Tammie L S Benzinger, Beau M Ances

Open Access Publications

The contributors to persistent cognitive impairment and hippocampal atrophy in leucine-rich glioma-inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [

Hope Springs Eternal: Can Project Echo Transform Nursing Homes?, Alice Bonner

Project ECHO Bibliography

No abstract provided.

Decoding Visual Information From High-Density Diffuse Optical Tomography Neuroimaging Data, Kalyan Tripathy, Zachary E Markow, Andrew K Fishell, Arefeh Sherafati, Tracy M Burns-Yocum, Mariel L Schroeder, Alexandra M Svoboda, Adam T Eggebrecht, Mark A Anastasio, Bradley L Schlaggar, Joseph P Culver

2020-Current year OA Pubs

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise …

Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a …

Genome-Wide Meta-Analysis Of Muscle Weakness Identifies 15 Susceptibility Loci In Older Men And Women, Garan Jones, Katerina Trajanoska, Adam J Santanasto, Najada Stringa, Chia-Ling Kuo, Janice L Atkins, Joshua R Lewis, Thuyvy Duong, Shengjun Hong, Mary L Biggs, Jian'an Luan, Chloe Sarnowski, Kathryn L Lunetta, Toshiko Tanaka, Mary K Wojczynski, Ryan Cvejkus, Maria Nethander, Sahar Ghasemi, Jingyun Yang, M Carola Zillikens, Stefan Walter, Kamil Sicinski, Erika Kague, Cheryl L Ackert-Bicknell, Dan E Arking, B Gwen Windham, Eric Boerwinkle, Megan L Grove, Misa Graff, Dominik Spira, Ilja Demuth, Nathalie Van Der Velde, Lisette C P G M De Groot, Bruce M Psaty, Michelle C Odden, Alison E Fohner, Claudia Langenberg, Nicholas J Wareham, Stefania Bandinelli, Natasja M Van Schoor, Martijn Huisman, Qihua Tan, Joseph Zmuda, Dan Mellström, Magnus Karlsson, David A Bennett, Aron S Buchman, Philip L De Jager, Andre G Uitterlinden, Uwe Völker, Thomas Kocher, Alexander Teumer, Leocadio Rodriguéz-Mañas, Francisco J García, José A Carnicero, Pamela Herd, Lars Bertram, Claes Ohlsson, Joanne M Murabito, David Melzer, George A Kuchel, Luigi Ferrucci, David Karasik, Fernando Rivadeneira, Douglas P Kiel, Luke C Pilling

Faculty, Staff and Student Publications

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10

Absent B Cells, Agammaglobulinemia, And Hypertrophic Cardiomyopathy In Folliculin-Interacting Protein 1 Deficiency, Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C Orellana, Grazia Fazio, Fred H Rodriguez, Loreani P Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G M Kroes, Daniele Moratto, Monique M Van Oostaijen-Ten Dam, Frank Baas, Silvère Van Der Maarel, Rocco Piazza, Zeynep H Coban-Akdemir, James R Lupski, Bo Yuan, Ivan K Chinn, Lucia Daxinger, Andrea Biondi

Faculty, Staff and Student Publications

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy …