Digital Commons Network^™

Identification Of Hypoxia-Inducible Factor Hif1a As A Therapeutic Target During Sars-Cov-2-Associated Lung Injury, Bentley Bobrow, Samuel D Luber, Paul Potnuru, Katherine Figarella, Jieun Kim, Yanyu Wang, In Hyuk Bang, David Robinson, Paulina B Sergot, Steven K Burke, Tingting Mills, Constanza De Dios, Robert Suchting, George W Williams, Adit A Ginde, Yafen Liang, Hongfang Liu, Charles Green, Marie-Francoise Doursout, Alparslan Turan, Daniel I Sessler, Xiaoyi Yuan, Holger K Eltzschig

Faculty, Staff and Student Publications

Hypoxia-inducible factors (HIFs) promote lung protection and pathogen eradication during acute lung injury. We therefore tested the theory that pharmacologic stabilization of HIFs dampens lung injury during SARS-CoV-2 pneumonia. Initial studies in murine SARS-CoV-2 models showed improved outcomes after treatment with the FDA-approved HIF-stabilizer vadadustat. Subsequent studies in genetic models implicated alveolar-expressed Hif1a in mediating lung protection. Therefore, we performed a randomized, double-blinded, multicenter phase 2 trial in patients admitted for SARS-CoV-2 infection and concomitant hypoxia (SpO2 ≤ 94%). Patients (n=448) were randomized to oral vadadustat (900 mg/day) or placebo for up to 14 days. Safety events were similar between …

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

Performance Of A Novel Stool Quantitative Polymerase Chain Reaction Assay For Pediatric Tuberculosis Detection In Sub-Saharan Africa, Anca Vasiliu, Lucia Carratala-Castro, Abigail Seeger, Joanna Ehrlich, Babongile Nkala, Tara Ness, Miguel Mario Cumbe, Durbbin Mulengwa, Shilzia Munguambe, Bariki Mtafya, Edson Mambuque, Nosisa Shiba, Sozinho Acacio, Lilian Komba, Clement Gascua Adu-Gyamfi, H Lester Kirchner, Christoph Lange, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Alexander Kay

Faculty, Staff and Students Publications

Background: Children have paucibacillary tuberculosis and cannot provide expectorated sputum. Invasive specimen collection, by gastric aspiration or sputum induction, has a low diagnostic yield. In this study, we aimed to evaluate the diagnostic performance and additive yield of a novel stool-based assay in children diagnosed with tuberculosis in sub-Saharan Africa.

Methods: We conducted a prospective case-control study from October 2020 to June 2023 in Eswatini, Mozambique, and Tanzania. Children under 15 years newly diagnosed with tuberculosis completed clinical examination, chest radiography, culture, sputum Xpert Ultra, stool Xpert Ultra, and stool-based quantitative polymerase chain reaction (stool qPCR) assessment. Stool qPCR sensitivity …

Adenovirus Species In U.S. Children With Acute Respiratory Illness, 2016-2019, Varvara Probst, Tess Stopczynski, Justin Z Amarin, Adam Gailani, Herdi K Rahman, Laura S Stewart, Rangaraj Selvarangan, Jennifer E Schuster, Marian G Michaels, John V Williams, Julie A Boom, Leila C Sahni, Vasanthi Avadhanula, Mary Allen Staat, Elizabeth P Schlaudecker, Christina Quigley, Christopher J Harrison, Mary E Moffatt, Geoffrey A Weinberg, Peter G Szilagyi, Janet A Englund, Eileen J Klein, Aaron T Curns, Heidi L Moline, Ariana P Toepfer, Susan I Gerber, James D Chappell, Andrew J Spieker, Natasha B Halasa

Faculty, Staff and Students Publications

Background: Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI). HAdV-B, -C, and -E species have been associated with ARI, though relative detection frequencies in United States (U.S.) and respective roles in symptomatic respiratory infections remain unclear.

Methods: We conducted a multicenter, prospective viral surveillance study at 7 U.S. children's hospitals comprising the New Vaccine Surveillance Network from January 12, 2016 to November 30, 2019. Children < 18 years old in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and respiratory specimens were tested for HAdV and other viral pathogens. HAdV-positive specimens were subsequently typed using single-plex real-time PCR assays targeting sequences in the hexon gene. Demographics, clinical characteristics, and outcomes (hospitalization and supplemental oxygen use as severity indicators) were compared between HAdV-B and HAdV-C species.

Results: Of the 29 381 children with ARI, 1843 (6.3%) had HAdV detected, with 1402 specimens (76.0%) successfully typed. HAdV-C was the most frequently detected species (73.0%), followed by HAdV-B …

Type I Interferon Protects Against Bone Loss In Periodontitis By Mitigating An Interleukin (Il)-17-Neutrophil Axis, Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang

Faculty, Staff and Student Publications

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory And Stool Samples With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Bada Yang, Hayley Poore, Alia Razid, Brittney Sweetser, Mathias Weis Damkjær, Alexander W Kay, Johanna Åhsberg, Ruvandhi R Nathavitharana, Ian Schiller, Nandini Dendukuri, Andreas Lundh, Maunank Shah, Stephanie Bjerrum, Devan Jaganath

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular assays widely used to diagnose tuberculosis disease in children. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended for use amongst children with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM separately in children, but in clinical practice the tests may be used concurrently, i.e. in 'parallel'.

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory and stool specimens in children, and with LF-LAM on urine amongst children with HIV, versus each assay alone for detecting pulmonary tuberculosis disease.

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Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests And Lateral Flow Urine Lipoarabinomannan Assays To Detect Tuberculosis Disease In Adults And Adolescents Living With Hiv, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Laura Olbrich, Mathias Weis Damkjær, Ruvandhi R Nathavitharana, Tobias Broger, Ioana Diana Olaru, Brittney Sweetser, Hayley Poore, Alia Razid, Alexander W Kay, Claudia M Denkinger, Ian Schiller, Nandini Dendukuri, Devan Jaganath, Andreas Lundh, Maunank Shah

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular World Health Organization (WHO)-recommended rapid diagnostic tests (also known as mWRDs) widely used to diagnose tuberculosis disease. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended by the WHO to assist in diagnosing tuberculosis disease amongst people with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM used in isolation for the detection of tuberculosis, but in clinical practice the tests may be used in parallel (i.e. LC-aNAAT in combination with LF-LAM).

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory …

Determining Accurate Pore Structures Of Polypropylene Membrane For Ecmo Using Fe-Sem Under Optimized Conditions, Makoto Fukuda, Yoshiaki Nishite, Eri Murata, Koki Namekawa, Tomohiro Mori, Tsutomu Tanaka, Kiyotaka Sakai

Children’s Nutrition Research Center Staff Publications

Long-term ECMOs are expected to be put into practical use in order to prepare for the next emerging severe infectious diseases after the novel coronavirus pandemic in 2019-2023. While polypropylene (PP) and polymethylpentene (PMP) are currently the mainstream materials for the hollow fiber membranes of ECMO, the PP membrane coated with a silicone layer on the outer surface has also been commercialized. In this study, we sought a method to accurately observe the detailed pore morphologies of the PP membrane by suppressing irreversible changes in the morphology in SEM observation, which is a general-purpose observation with higher resolution. As a …

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and …

Present And Future Of Microbiome-Targeting Therapeutics, Lauren E Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A Britton, Anthony W Maresso, Geoffrey A Preidis

Children’s Nutrition Research Center Staff Publications

A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, …

Computerized Diagnostic Decision Support Systems-Isabel Pro Versus Chatgpt-4 Part Ii, Joe M Bridges, Xiaoqian Jiang, Michael Ige, Oluwatoniloba Toyobo

Faculty, Staff and Student Publications

Objective: Does a Tree-of-Thought prompt and reconsideration of Isabel Pro's differential improve ChatGPT-4's accuracy; does increasing expert panel size improve ChatGPT-4's accuracy; does ChatGPT-4 produce consistent outputs in sequential requests; what is the frequency of fabricated references?

Materials and methods: Isabel Pro, a computerized diagnostic decision support system, and ChatGPT-4, a large language model. Using 201 cases from the New England Journal of Medicine, each system produced a differential diagnosis ranked by likelihood. Statistics were Mean Reciprocal Rank, Recall at Rank, Average Rank, Number of Correct Diagnoses, and Rank Improvement. For reproducibility, the study compared the initial expert panel run …

Allergic Fungal Rhinosinusitis Diagnosis, Management, Associated Conditions, Pathophysiology, And Future Directions: Summary Of A Multidisciplinary Workshop, Lauren T Roland, Cecelia Damask, Amber U Luong, Antoine Azar, Charles S Ebert, Thomas Edwards, Katherine N Cahill, Do-Yeon Cho, David Corry, Tara L Croston, Alexandra F Freeman, Amin Javer, Paneez Khoury, Jean Kim, Michael Koval, Edward D Mccoul, James W Mims, Anju Peters, Jay F Piccirillo, Richard P Ramonell, Amali Samarasinghe, Robert P Schleimer, Prestina Smith-Davidson, Andrej Spec, Michael E Wechsler, Sarah K Wise, Joshua M Levy

The Brown Foundation: Institute of Molecular Medicine

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research …

Allergic Fungal Rhinosinusitis Diagnosis, Management, Associated Conditions, Pathophysiology, And Future Directions: Summary Of A Multidisciplinary Workshop, Lauren T Roland, Cecelia Damask, Amber U Luong, Antoine Azar, Charles S Ebert, Thomas Edwards, Katherine N Cahill, Do-Yeon Cho, David Corry, Tara L Croston, Alexandra F Freeman, Amin Javer, Paneez Khoury, Jean Kim, Michael Koval, Edward D Mccoul, James W Mims, Anju Peters, Jay F Piccirillo, Richard P Ramonell, Amali Samarasinghe, Robert P Schleimer, Prestina Smith-Davidson, Andrej Spec, Michael E Wechsler, Sarah K Wise, Joshua M Levy

The Brown Foundation: Institute of Molecular Medicine

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research …

Association Of Sirt6 Expression With Risk Of Pneumonitis Induced By Radiotherapy In Cancer Patients, Fengyuan Yu, Zheng Gong, Yuan Li, Danial F Naseem, Chen Li, Miaowei Wen, Bingying Zhao, Zhezhe Xu, Shanshan Zhang, Rukun Zang, Ailu Wu, Qingxin Han, Shuhui Wu, Hongwei Li, Yipeng Song

Faculty, Staff and Student Publications

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Gut Microbiota In Immuno-Oncology: A Practical Guide For Medical Oncologists With A Focus On Antibiotics Stewardship, Arielle Elkrief, Bertrand Routy, Lisa Derosa, Laura Bolte, Jennifer A Wargo, Jennifer L Mcquade, Laurence Zitvogel

Faculty, Staff and Student Publications

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the …

Biomolecular Condensates In Immune Cell Fate, Srikanth Kodali, Caroline M Sands, Lei Guo, Yun Huang, Bruno Di Stefano

Faculty, Staff and Students Publications

Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory proteins. Findings have established a link between condensate formation and the gene regulatory networks that ensure the proper development of immune cells. Conversely, condensate dysregulation has been linked to impaired immune cell fates, including ageing and malignant transformation. This Review …

Dermatologic Fungal Neglected Tropical Diseases-Part I Epidemiology And Clinical Features, Kaya L Curtis, Jeremy A W Gold, Jana M Ritter, Theodore Rosen, Daniel Wagner C L Santos, Dallas J Smith, Shari R Lipner

Faculty, Staff and Students Publications

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization, cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate …

Fine-Scale Population Structure Of Japanese Helicobacter Pylori Provides New Anthropological And Epidemiological Insights, Kohei Tomonari, Batsaikhan Saruuljavkhlan, Ricky Indra Alfaray, Kartika Afrida Fauzia, Osamu Matsunari, Daisuke Chinda, Tadashi Shimoyama, Phawinee Subsomwong, Nagisa Kinjo, Tetsu Kinjo, Yasuo Hanamure, Masato Shinzato, Rumiko Suzuki, Fukunori Kinjo, Shigeru Takigami, Toshio Fujioka, Takeshi Matsuhisa, Junko Akada, Takashi Matsumoto, Yoshio Yamaoka

Faculty, Staff and Students Publications

Helicobacter pylori is considered to contribute to gastric cancer and is also used as a marker to trace human migration due to its co-evolution with humans. To understand the recently proposed tripartite model suggesting three ancestral origins for the Japanese population and address the enigma of the high incidence of gastric cancer in Northeast Hondo (Hondo is mainland Japan), we conducted a fine-scale population structure analysis using a large Japanese H. pylori dataset, including 438 strains from 9 regions based on whole-genome sequences. As a result of fineSTRUCTURE analysis, it was found that H. pylori in Northeast Hondo is genetically …

Plasma Microbial Cell-Free Dna Sequencing For The Detection Of Kingella Kingae Pediatric Spinal Infections, Asim A Ahmed, Sarah Y Park, Matthew J Smollin, Martin S Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R Cotilla, Marian E Melish, Connie Trieu, Nazia A Kabani, Joshua Cooper, Audrey R Lloyd, David W Kimberlin, John C Arnold, Alejandro Jordan-Villegas, Lori E Patterson, Catherine E Foster, Pablo Yagupsky

Faculty, Staff and Students Publications

Background: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae .

Methods: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age < 18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis …

Airway Immune Signatures In Severe And Fatal Infection With Covid-19, Naresh Doni Jayavelu, Jing Jing Qi, Slim Fourati, Farrah Kheradmand, Charles R Langelier, Lauren I R Ehrlich, Joann Diray-Arce, Annmarie Hoch, Monica Kraft, Patrice M Becker, Matthew C Altman, Ruth R Montgomery

Faculty, Staff and Students Publications

No abstract provided.

Performance Of Stool-Based Molecular Tests And Processing Methods For Paediatric Tuberculosis Diagnosis: A Systematic Review And Meta-Analysis, Lucía Carratalà-Castro, Shilzia Munguambe, Belén Saavedra-Cervera, Petra De Haas, Alexander Kay, Olivier Marcy, Pamela Nabeta, Willy Ssengooba, Elisabetta Ghimenton-Walters, Sozinho Acácio, Maryline Bonnet, Joanna Ehrlich, Andrew R Dinardo, Anca Vasiliu, Christoph Lange, Sabine Hermans, Anna M Mandalakas, Elisa López-Varela, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase …

Dosing Recommendations For Ampicillin And Ceftriaxone In The Treatment Of Pediatric Community-Acquired Pneumonia Using Monte Carlo- And Physiologic-Based Pharmacokinetic Simulations, Norint Tung, Dustin Huynh, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Tyler H Do, Amartya Setty, Lana Hoang, John S Bradley, Jennifer Le

Faculty, Staff and Students Publications

Objective: Since 2011, Ampicillin (AMP) has been recommended as the parenteral antibiotic of choice for pediatric community-acquired pneumonia (CAP), but ceftriaxone (CRO) is recommended for unvaccinated children and those with complicated CAP. Using penicillin and CRO susceptibility data for pneumococcus, we evaluated the adequacy of currently recommended doses of AMP and CRO.

Methods: With nonlinear mixed-effects modeling v7.3, Monte Carlo simulations (MCS, N = 10,000) for AMP and CRO were conducted for 6 virtual patients aged 3 months, 1, 2, 5, 10, and 15 years. PK-Sim v9.0 was used to develop physiologic-based pharmacokinetic (PBPK) models for AMP (N = 4000) …

40 Years After The Discovery Of Helicobacter Pylori: Performing Optimized “Subtraction” For Clinical Eradication, Yi Hu, Ren-Chun Du, Yong-Kang Lai, Yu-Xin Hu, Yu-Chen Zhu, Yan-An Zhou, Chun-Xi Shu, Bo Zhou, Li-Xiang Ling, Xu Shu, Yong Xie, James Y W Lau, Yin Zhu, David Y Graham, Nong-Hua Lu

Faculty, Staff and Students Publications

It has been 40 years since the first discovery of the important human pathogen, Helicobacter pylori (H. pylori). Eradication of the infection continues to pose significant challenges in part because of the global increase in antibiotic resistance. Generally, the “addition” strategy has failed to deliver the desired results for more than a short period and often contributed to the increase in the prevalence of resistant strains. As such, optimization of each component of the treatment strategy has become an increasingly critical focus of research. In this study, we summarized the evolution of H. pylori eradication regimens and the …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Post-Recovery Viral Shedding Shapes Wastewater-Based Epidemiological Inferences, Tin Phan, Samantha Brozak, Bruce Pell, Stanca M Ciupe, Ruian Ke, Ruy M Ribeiro, Anna Gitter, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Background: The prolonged viral shedding from the gastrointestinal tract is well documented for numerous pathogens, including SARS-CoV-2. However, the impact of prolonged viral shedding on epidemiological inferences using wastewater data is not yet fully understood.

Methods: To gain a better understanding of this phenomenon at the population level, we extended a wastewater-based modeling framework that integrates viral shedding dynamics, viral load data in wastewater, case report data, and an epidemic model.

Results: Our results indicate that as an outbreak progresses, the viral load from recovered individuals gradually becomes predominant, surpassing that from the infectious population. This phenomenon leads to a …

Turning Analysis Into Action: Opportunities And Challenges In Implementing Wastewater Science For Public Health Decision-Making, Anna Gitter, Valeria Ruvalcaba, Katelyn Clark, Theresa Tran Carapucci, Fuqing Wu, Blake M Hanson, Jennifer Deegan, John Balliew, Eric Boerwinkle, Anthony W Maresso, Kristina D Mena

Faculty, Staff and Students Publications

In the 5 years since the emergence of the COVID-19 pandemic, the field of wastewater-based epidemiology (WBE) has dramatically expanded with programs implemented across the globe to monitor for SARS-CoV-2 and other viruses of public health concern. However, the best way to use wastewater surveillance data and inform local communities of the utility of wastewater science remains limited and sporadically discussed. Specifically, there is vague guidance regarding interpreting varying levels of viral loads in wastewater for public health significance. While collaborative efforts are key to implementing these community-specific wastewater surveillance programs, effectively using the data for public health decision-making still …

Are We Ready For Ai-Augmented Generalists?, Jiajie Zhang

Faculty, Staff and Student Publications

Artificial Intelligence (AI) is reshaping medical practice and education by unifying the knowledge of medical specialties and subspecialties into a single, intelligent system. This system functions not only as an integrated knowledge base but also as an active cognitive collaborator. By bridging knowledge gaps beyond the capacity of any individual clinician, AI could enable physicians to function as AI-augmented generalists who can perform certain tasks that require specialist training. These generalists may help mitigate care fragmentation, but realizing their potential will require significant changes in medical education.