Digital Commons Network^™

Normative Laboratory Value Ranges In Pediatric Patients Who Underwent Evaluation For Mis-C, Thomas Graf, Nathan M Money, Sindhoosha Malay, Nori Minich, Risa Bochner, Bari Winik, Ron Kaplan, Jennifer Y Colgan, Erin Aldag, Ryan O' Sullivan, Guliz Erdem, Allayne Stephans

Faculty, Staff and Student Publications

Background and objectives: Diagnosis of multisystem inflammatory syndrome in children (MIS-C) is challenging due to symptom overlap with other common conditions. The primary objective of this multicenter study was to establish normative laboratory values in MIS-C patients and compare to patients evaluated for MIS-C who had other final diagnoses.

Methods: Five hospitals reviewed records of a cohort of patients 6 months to 18 years old who were evaluated for MIS-C between March 31st 2020 and February 1st 2022. Patient demographics, clinical presentation, and laboratory values were compared in patients with a final diagnosis of MIS-C versus all other conditions. Patients' …

Invasive Fungal Disease In Solid Organ And Hematopoietic Cell Transplant Recipients, United States, Jeremy A W Gold, Kaitlin Benedict, Elizabeth Sajewski, Tom Chiller, Meghan Lyman, Mitsuru Toda, Jessica S Little, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Background: Updated benchmark data on invasive fungal disease (IFD) in solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) recipients are necessary to increase clinical recognition and inform treatment and prevention strategies. We estimated IFD incidence and potential risk factors in transplant recipients in a large US commercial health insurance database.

Methods: We observed patients who received SOT or HCT during 2018-2022 until IFD development, disenrollment, or database end date (July 31, 2023). We calculated incidence (per 1000 person-years) and time to IFD development, comparing demographic features and underlying conditions for IFD versus non-IFD patients.

Results: Overall, 9143 patients received …

National Healthcare Safety Network… We Need To Talk…., Misti Ellsworth, Luis Zeichner Ostrosky, Bela Patel, Robert Yetman, Phillip Chang

Faculty, Staff and Student Publications

No abstract provided.

Development, Delivery, And Evaluation Of The Texas Epidemic Public Health Institute Pilot Infection Control Lecture Series, Kayla E Ruch, Anabel Rodriguez, Janelle Rios, Luis Ostrosky-Zeichner, Eric L Brown

Faculty, Staff and Student Publications

Introduction: The Texas Epidemic Public Health Institute (TEPHI) aims to keep Texans healthy and the economy strong by preparing for the next infectious disease outbreak. TEPHI's Small Rural Healthcare Preparedness core developed, delivered, and evaluated a pilot infection prevention and control webinar series called Infection Control for rural-serving health professionals and organizations based on infection prevention and control field best practices.

Methods: Data from the first year of the Infection Control series was collected through attendee registration forms, attendance records, knowledge, and post-lecture evaluation surveys using Qualtrics. The data were analyzed using Qualtrics software. Lectures were free and open to …

Rates Of Multidrug-Resistant Gram-Negative Bacterial Infections In Hospitalized Non-Immunocompromised Pediatric Patients: A 9-Year Retrospective Study At A Lebanese Tertiary Medical Center, Ramia Zakhour, Sarah Khafaja, Rawan Korman, Celina F Boutros, Zeinab El Zein, Ahmad Chmaisse, Magda Haj, Amani Haddara, Zeina El-Houry, Malak Jbahi, Sarah Chamseddine, Samer Bou Karroum, Dana Al Oweini, Yolla Salama Youssef, Nour Youssef, Mayse Nasser, Danielle Fayad, Farida Abi Farraj, Clara El Nakib, Imad Isaac, Mireille Lteif, George F Araj, Ghassan S Dbaibo

Faculty, Staff and Student Publications

Introduction: Multidrug resistant (MDR) Gram-negative bacterial infections are considered a major public health threat. The objectives of this study were to describe the epidemiology, potential contributing factors, and antimicrobial resistance patterns associated with infections caused by MDR Gram-negative bacteria (GNB) in non-immunocompromised children and adolescents.

Methods: This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included non-immunocompromised patients 18 years of age or younger with infections caused by GNB isolated from a sterile site or nonsterile site in the setting of clinical infection.

Results: A total of …

Decline In Attrition Rates In United States Pediatric Residency And Fellowship Programs, 2007–2020: A Repeated Cross-Sectional Study, Emma Omoruyi, Greg Russell, Kimberly Montez

Faculty, Staff and Student Publications

Purpose: Declining fill rates in US pediatric residency and subspecialty programs requires trainee retention. Attrition, defined as transfers, withdrawals, dismissals, unsuccessful completions, or deaths, disrupts program function and impacts the pediatric workforce pipeline. It aims to evaluate attrition trends among pediatric residents and fellows in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs from 2007 to 2020.

Methods: This repeated cross-sectional study analyzed publicly available ACGME Data Resource Book records. Attrition rates and 95% confidence intervals (CIs) were calculated overall and by subspecialty. Logistic regression assessed temporal changes; odds ratios (ORs) compared 2020 to 2007.

Results: From 2007-2020, pediatric residents …

Revisiting Cytomegalovirus In Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: Current Strategies For Prevention And Management In The Letermovir Era, Lisa Hiskey, Diego R Hijano, Ramia Zakhour

Faculty, Staff and Student Publications

CMV infection remains the most common clinically significant infection in pediatric allogeneic hematopoietic stem cell (HCT) recipients, with seropositive recipients of transplants from seronegative donors at the highest risk for complications. In recent years, letermovir, a novel antiviral with a favorable toxicity profile, was approved first for adults and more recently for pediatric patients for the primary prophylaxis of CMV infection and disease in high-risk HCT recipients. Growing evidence from real-life data regarding the safety and efficacy of letermovir has transformed the landscape of CMV disease in HCT transplant recipients and led to a paradigm shift from a preemptive approach …

Smoking Habit And Long-Term Colorectal Cancer Incidence By Exome-Wide Mutational And Neoantigen Loads: Evidence Based On The Prospective Cohort Incident-Tumour Biobank Method, Tsuyoshi Hamada, Tomotaka Ugai, Carino Gurjao, Satoko Ugai, Xuehong Zhang, Koichiro Haruki, Yasutoshi Takashima, Naohiko Akimoto, Mai Chan Lau, Kosuke Matsuda, Nobuhiro Nakazawa, Mayu Higashioka, Satoshi Miyahara, Keisuke Kosumi, Yohei Masugi, Li Liu, Yin Cao, Daniel Nevo, Molin Wang, Reiko Nishihara, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Jeffrey A Meyerhardt, Edward L Giovannucci, Jonathan A Nowak, Charles S Fuchs, Andrew T Chan, Mingyang Song, Marios Giannakis, Shuji Ogino

Faculty, Staff and Student Publications

Objective: To test the hypothesis that the association of smoking with long-term colorectal cancer incidence may be stronger for tumours with higher mutational and neoantigen loads.

Methods and analysis: In the Nurses' Health Study (1980-2012) and the Health Professionals Follow-up Study (1986-2012), our novel prospective cohort incident-tumour biobank method (PCIBM) used 3053 incident colorectal carcinoma cases including 752 cases with whole-exome sequencing data. Using the multivariable duplication-method Cox regression model with the inverse probability weighting to adjust for the selection bias due to tissue availability, we assessed a differential association of cigarette smoking with colorectal carcinoma incidence by an exome-wide …

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior

Faculty, Staff and Student Publications

No abstract provided.

Burden Of Seasonal Human Coronavirus Infections In Hematopoietic Cell Transplant Recipients, Fareed Khawaja, Terri Lynn Shigle, Layale Yaghi, May Daher, Jeremy L Ramdial, Ella Ariza-Heredia, Ying Jiang, Roy F Chemaly

Faculty, Staff and Student Publications

Background: Community respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.

Methods: We performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respiratory viral infections in HCT recipients. Patient data were collected to identify risk factors for HCoV LRI, and to calculate …

Effectiveness And Acceptability Of Ventilation Modifications In Healthcare Facilities, Liberia 2022–2023, Ronan F Arthur, Ashley Styczynski, Krithika Srinivasan, Amos Tandanpolie, Philip Bemah, Ethan Bell, Jason R Andrews, Tom Baer, Jorge L Salinas

Faculty, Staff and Student Publications

Objective: To evaluate the effectiveness and acceptability of ventilation interventions in naturally ventilated hospitals in Liberia.

Design: Difference-in-differences analysis of pre- and post-air changes per hour of intervention and control spaces.

Setting: Hospitals in Bong and Montserrado Counties, Liberia.

Participants: Seventy patient care spaces were evaluated at baseline. Six spaces underwent physical intervention modifications, while 2 spaces were assessed for indirect effects and 2 others used as controls. Healthcare workers were interviewed to assess ventilation knowledge and acceptability.

Interventions: Ventilation interventions included the installation of window screens, louvered doors and windows, and wind turbines.

Methods: We measured carbon dioxide levels …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

Staphylococcus Epidermidis St2 Strains Associated With Bloodstream Infections Contain A Unique Mobile Genetic Element Encoding A Plasmin Inhibitor, Amy A Gomez, Clara Kjerfve, Minseo Choi, Wen Liu, Kelly Churion, Sheila Thomas, Holger Rohde, Sam Shelburne, Jon T Skare, Magnus Hook, Srishtee Arora

Faculty, Staff and Student Publications

Staphylococcus epidermidis, a common commensal bacterium, is a leading cause of nosocomial catheter-associated bloodstream infections. S. epidermidis sequence type 2 (ST2) is specifically recognized globally for causing invasive disease. In this study, we identified a novel putative integrated conjugative element, pICE-Sepi-ST2, unique to the genomes of S. epidermidis ST2. Our investigation identified pICE-Sepi-ST2 in all ST2 isolates from bloodstream infections. Meanwhile, ST2 isolates from other infection sources, such as catheters, prosthetic joints, and fracture fixations, showed variable pICE-Sepi-ST2 prevalence. pICE-Sepi-ST2 encodes two putative cell wall anchored proteins that we have designated SesX and SesY. Biochemical characterization of SesY revealed …

Nomenclature For Human And Animal Fungal Pathogens And Diseases: A Proposal For Standardized Terminology, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Maiken Cavling Arendrup, Andrew Borman, Sharon Chen, Anuradha Chowdhary, Robert C Colgrove, Oliver A Cornely, David W Denning, Philippe J Dufresne, Laura Filkins, Jean-Pierre Gangneux, Josepa Gené, Andreas H Groll, Jaques Guillot, Gerhard Haase, Catriona Halliday, David L Hawksworth, Roderick Hay, Martin Hoenigl, Vit Hubka, Tomasz Jagielski, Hazal Kandemir, Sarah E Kidd, Julianne V Kus, June Kwon-Chung, Shawn R Lockhart, Jacques F Meis, Leonel Mendoza, Wieland Meyer, M Hong Nguyen, Yinggai Song, Tania C Sorrell, J Benjamin Stielow, Rachel Vilela, Roxana G Vitale, Nancy L Wengenack, P Lewis White, Luis Ostrosky-Zeichner, Sean X Zhang

Faculty, Staff and Student Publications

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately …

Effect Of School Hpv Vaccination Requirements On Pediatricians' Recommendations, Ashley Hedrick Mckenzie, Lara S Savas, Ross Shegog, Dale S Mantey, Erica L Frost, Paul Gerardo Yeh, C Mary Healy, Stanley Spinner, L Aubree Shay, Sharice M Preston, Sally W Vernon

Faculty, Staff and Student Publications

Background/objectives: Pediatrician recommendations are highly influential in parents’ decisions to vaccinate their children against HPV. Unqualified, presumptive, and bundled recommendations (UPBRs) are associated with increased HPV vaccine uptake and are considered best practice. This study analyzes pediatricians’ self-reported data to assess changes in UPBR use and the psychosocial determinants of UPBR use as a result of the implementation of a multi-level intervention, the Adolescent Vaccination Program (AVP).

Methods: We surveyed pediatricians across 51 clinics in the Houston area. Baseline surveys (n = 137) were distributed in 2015, and follow-ups (n = 120) in 2019.

Results: Pediatrician UPBR use …

Liar-Dependent Gene Expression Contributes To Antimicrobial Responses In Group A, Luis Alberto Vega, Misú Sanson-Iglesias, Piyali Mukherjee, Kyle D Buchan, Gretchen Morrison, Anne E Hohlt, Anthony R Flores

Faculty, Staff and Student Publications

The ability to sense and respond to host defenses is essential for pathogen survival. Some mechanisms involve two-component systems (TCSs) that respond to host molecules, such as antimicrobial peptides (AMPs), and activate specific gene regulatory pathways to aid in survival. Alongside TCSs, bacteria coordinate cell division proteins, chaperones, cell wall sortases, and secretory translocons at discrete locations within the cytoplasmic membrane, referred to as functional membrane microdomains (FMMs). In group A Streptococcus (GAS), the FMM or “ExPortal” coordinates protein secretion, cell wall synthesis, and sensing of AMP-mediated cell envelope stress via the LiaFSR three-component system. Previously, we showed that GAS …

Comparative Analysis Of Indices For Social Determinants Of Health In Pediatric Surgical Populations, Caroline Q Stephens, Ava Yap, Lan Vu, Jacqueline M Saito, Dwight Barry, Amy M Shui, Hannah Cockrell, Sarah Cairo, Derek Wakeman, Loren Berman, Sarah Greenberg, Allison F Linden, Jonathan Kohler, Kuojen Tsao, Nicole A Wilson

Faculty, Staff and Student Publications

Importance: Conclusions vary substantially among studies examining associations between area-based social determinants of health (SDOH) and pediatric health disparities based on the selected patient population and SDOH index. Most national studies use zip codes, which encompass a wide distribution of communities, limiting the generalizability of findings.

Objectives: To characterize the distributions of composite SDOH indices for pediatric surgical patients within a national sample of academic children's hospitals and to assess SDOH index precision in classifying patients at similar levels of disadvantage.

Design, setting, and participants: This multicenter retrospective cohort study included patients younger than 18 years who underwent surgery from …

Navigating Physical Activity Promotion And Policy In The Post-Covid-19-Pandemic Era, Justin Richards, Katja Siefken, Michael Pratt, Adrian Bauman, Juliana Mejía-Grueso, Catherine B Woods, Wanda Wendel-Vos, Erica Hinckson, Deborah Salvo, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Background: There is limited evidence on the priorities and opportunities associated with promoting population physical activity (PA) participation for the post-COVID-19-pandemic future.

Purpose: This study assessed government-led PA promotion efforts before and during the COVID-19 pandemic, along with post-COVID-19-pandemic priorities and recommendations.

Methods: Two separate cross-sectional surveys conducted in 2023. Survey 1 was targeted at the Global Observatory for Physical Activity (GoPA!) Country Contacts. Survey 2 also included key international informants representing influential stakeholders in PA policy implementation.

Results: There were 68 respondents to Survey 1, collectively representing 61 countries. An additional 37 people, including representatives from 14 key international …

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …

Surfactant Protein-C Regulates Alveolar Type 2 Epithelial Cell Lineages Via The Cd74 Receptor, Krishan G Jain, Yang Liu, Runzhen Zhao, Preeti J Muire, Nan-Miles Xi, Hong-Long Ji

Faculty, Staff and Student Publications

Background: Deficiency of surfactant protein-C (SPC) increases susceptibility to lung infections and injury, and suppressed expression of SPC has been associated with the severity of acute respiratory distress syndrome (ARDS). Alveolar type 2 epithelial cells (AT2) are critical for maintenance and repair of the lung. However, the role of the SPC in the regulation of AT2 cell lineage and the underlying mechanisms are not completely understood.

Methods: This study aimed to investigate the mechanisms by which SPC regulates AT2 lineages. Sftpc-/- mice were used to model the SPC deficiency in ARDS patients. We utilized three-dimensional (3D) organoids to compare AT2 …

Nasal Virus Infection Induces Asthma Exacerbation Through B-Cell-Dependent Recruitment Of Inflammatory Monocytes, Kody A Waldstein, Arman Issimov, Maria Ganama, Valerie Jinge, Stephen Tilley, Xiaoyang Hua

Faculty, Staff and Student Publications

Background: Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.

Methods: In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.

Results: Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted …

Neurohospitalist Core Competencies, Jana J Wold, Jetter Robertson, Jerome A Jeevarajan, Molly G Knox, Prateek Thatikunta, Guillermo E Solorzano, Kristin Galetta, Shefali Dujari, Tarini Goyal, Matthew E Ehrlich, Jonathan P Donnelly, Elizabeth Marriott, Vishal A Mandge, Roshni S Dhoot, Matthew W Luedke, Matthew B Maas, Margaret Y Yu, Michel Toledano, Rafid Mustafa, Jamie L Palaganas, Kathryn Kvam, Rachelle Dugue, Ethan Meltzer, Lahoud Touma, Maulik P Shah, Vanja C Douglas, Karen Orjuela, Brian J Scott, Joshua P Klein, David J Likosky, Jennifer R Simpson, Megan B Richie, Carolin Dohle, Jane G Morris, Carl A Gold

Faculty, Staff and Student Publications

The Neurohospitalist Core Competencies comprise a set of competency-based learning objectives that encapsulate the knowledge, skills, and attitudes of neurohospitalitists who specialize in the care of hospitalized patients with neurologic conditions. These competencies serve to characterize the rapidly expanding field of neurohospitalist medicine. The 27 chapters are divided into 3 sections entitled: neurological conditions, clinical interventions and interpretation of ancillary studies, and neurohospitalist role in the healthcare system. Each individual learning objective in the chapters describes a specific concept with an action verb to illustrate the behavior that the neurohospitalist exhibits. The individual neurohospitalist may not exhibit mastery in each …

The Impact Of Diabetes Mellitus On Hiv Virologic Control: Results Of The Macs/Wihs Combined Cohort Study, Sarah C Mann, Weiqun Tong, Alison G Abraham, Frank Palella, Anjali Sharma, Phyllis C Tien, Margaret A Fischl, Samy I Mcfarlane, Cecile D Lahiri, Susan Koletar, Daniel Merenstein, Michelle Floris-Moore, Jordan E Lake, Elizabeth Daubert, Aubri Hickman, Todd T Brown, Jose Castillo-Mancilla

Faculty, Staff and Student Publications

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the …

Systematic Review Of Immune Checkpoint Inhibitor-Related Gastrointestinal, Hepatobiliary, And Pancreatic Adverse Events, Malek Shatila, Hao Chi Zhang, Anusha Shirwaikar Thomas, Antonio Pizuorno Machado, Sidra Naz, Nitish Mittal, Christine Catinis, Krishnavathana Varatharajalu, Carolina Colli Cruz, Eric Lu, Deanna Wu, Julie R Brahmer, Franck Carbonnel, Stephen B Hanauer, Bret Lashner, Bryan Schneider, John A Thompson, Michel Obeid, David P Farris, Yinghong Wang

Faculty, Staff and Student Publications

Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity …

The 2024 Report Of The Lancet Countdown On Health And Climate Change: Facing Record-Breaking Threats From Delayed Action, Marina Romanello, Maria Walawender, Shih-Che Hsu, Annalyse Moskeland, Yasna Palmeiro-Silva, Daniel Scamman, Zakari Ali, Nadia Ameli, Denitsa Angelova, Sonja Ayeb-Karlsson, Sara Basart, Jessica Beagley, Paul J Beggs, Luciana Blanco-Villafuerte, Wenjia Cai, Max Callaghan, Diarmid Campbell-Lendrum, Jonathan D Chambers, Victoria Chicmana-Zapata, Lingzhi Chu, Troy J Cross, Kim R Van Daalen, Carole Dalin, Niheer Dasandi, Shouro Dasgupta, Michael Davies, Robert Dubrow, Matthew J Eckelman, James D Ford, Chris Freyberg, Olga Gasparyan, Georgiana Gordon-Strachan, Michael Grubb, Samuel H Gunther, Ian Hamilton, Yun Hang, Risto Hänninen, Stella Hartinger, Kehan He, Julian Heidecke, Jeremy J Hess, Louis Jamart, Slava Jankin, Harshavardhan Jatkar, Ollie Jay, Ilan Kelman, Harry Kennard, Gregor Kiesewetter, Patrick Kinney, Dominic Kniveton, Rostislav Kouznetsov, Pete Lampard, Jason K W Lee, Bruno Lemke, Bo Li, Yang Liu, Zhao Liu, Alba Llabrés-Brustenga, Melissa Lott, Rachel Lowe, Jaime Martinez-Urtaza, Mark Maslin, Lucy Mcallister, Celia Mcmichael, Zhifu Mi, James Milner, Kelton Minor, Jan Minx, Nahid Mohajeri, Natalie C Momen, Maziar Moradi-Lakeh, Karyn Morrisey, Simon Munzert, Kris A Murray, Nick Obradovich, Megan B O'Hare, Camile Oliveira, Tadj Oreszczyn, Matthias Otto, Fereidoon Owfi, Olivia L Pearman, Frank Pega, Andrew J Perishing, Ana-Catarina Pinho-Gomes, Jamie Ponmattam, Mahnaz Rabbaniha, Jamie Rickman, Elizabeth Robinson, Joacim Rocklöv, David Rojas-Rueda, Renee N Salas, Jan C Semenza, Jodi D Sherman, Joy Shumake-Guillemot, Pratik Singh, Henrik Sjödin, Jessica Slater, Mikhail Sofiev, Cecilia Sorensen, Marco Springmann, Zélie Stalhandske, Jennifer D Stowell, Meisam Tabatabaei, Jonathon Taylor, Daniel Tong, Cathryn Tonne, Marina Treskova, Joaquin A Trinanes, Andreas Uppstu, Fabian Wagner, Laura Warnecke, Hannah Whitcombe, Peng Xian, Carol Zavaleta-Cortijo, Chi Zhang, Ran Zhang, Shihui Zhang, Ying Zhang, Qiao Zhu, Peng Gong, Hugh Montgomery, Anthony Costello

Faculty, Staff and Student Publications

Despite the initial hope inspired by the 2015 Paris Agreement, the world is now dangerously close to breaching its target of limiting global multiyear mean heating to 1·5°C. Annual mean surface temperature reached a record high of 1·45°C above the pre-industrial baseline in 2023, and new temperature highs were recorded throughout 2024. The resulting climatic extremes are increasingly claiming lives and livelihoods worldwide.

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Diaphragmatic Myopathy Associated With Dual Immune Checkpoint Inhibitors In A Patient With Renal Cell Carcinoma, Jeremy R Walder, Saadia A Faiz, Sudhakar Tummala, Shiao-Pei Weathers, Nicolas L Palaskas, Maryam Buni, Ajay Sheshadri, Lara Bashoura

Faculty, Staff and Student Publications

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated …