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Benefits Of Newborn Screening And Hematopoietic Cell Transplant In Infantile Krabbe Disease, Kristin M Page, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, Jennifer Rubin, Shalini Shenoy, Joanne Kurtzberg May 2022

Benefits Of Newborn Screening And Hematopoietic Cell Transplant In Infantile Krabbe Disease, Kristin M Page, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, Jennifer Rubin, Shalini Shenoy, Joanne Kurtzberg

Open Access Publications

Infantile Krabbe disease (IKD) can be treated with hematopoietic cell transplantation (HCT) if done during the first weeks of life before symptoms develop. To facilitate this, newborn screening (NBS) has been instituted in 8 US states. An application to add IKD to the recommended NBS panel is currently under review. In this report, the outcomes of newborns with IKD diagnosed through NBS and treated with HCT are presented. The unique challenges associated with NBS for this disease are discussed, including opportunities for earlier diagnosis and streamlining treatment referrals. This is a retrospective review of six infants with IKD detected by …


Strategies To Limit Invasive Fungal Infection In A Coronavirus Disease 2019 (Covid-19) Intensive Care Unit: The Role Of Infection Prevention For Renovation And Construction In Resource-Limited Settings, Ornnicha Sathitakorn, Surachai Chaononghin, Panipak Katawethiwong, Thanus Pientong, David J. Weber, David K. Warren, Piyaporn Apisarnthanarak, Anucha Apisarnthanarak May 2022

Strategies To Limit Invasive Fungal Infection In A Coronavirus Disease 2019 (Covid-19) Intensive Care Unit: The Role Of Infection Prevention For Renovation And Construction In Resource-Limited Settings, Ornnicha Sathitakorn, Surachai Chaononghin, Panipak Katawethiwong, Thanus Pientong, David J. Weber, David K. Warren, Piyaporn Apisarnthanarak, Anucha Apisarnthanarak

Open Access Publications

No abstract provided.


Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin May 2022

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Open Access Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …


Association Of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events And Health Care Expenditures, Anne M Butler, Derek S Brown, Michael J Durkin, John M Sahrmann, Katelin B Nickel, Caroline A O'Neil, Margaret A Olsen, David Y Hyun, Rachel M Zetts, Jason G Newland May 2022

Association Of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events And Health Care Expenditures, Anne M Butler, Derek S Brown, Michael J Durkin, John M Sahrmann, Katelin B Nickel, Caroline A O'Neil, Margaret A Olsen, David Y Hyun, Rachel M Zetts, Jason G Newland

2020-Current year OA Pubs

Importance: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described.

Objective: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

Design, Setting, and Participants: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. …


Endogenous Metabolic Markers For Predicting The Activity Of Dihydropyrimidine Dehydrogenase, Jihyun Kang, Andrew Hyoungjin Kim, Inseung Jeon, Jaeseong Oh, In-Jin Jang, Seunghwan Lee, Joo-Youn Cho May 2022

Endogenous Metabolic Markers For Predicting The Activity Of Dihydropyrimidine Dehydrogenase, Jihyun Kang, Andrew Hyoungjin Kim, Inseung Jeon, Jaeseong Oh, In-Jin Jang, Seunghwan Lee, Joo-Youn Cho

2020-Current year OA Pubs

Five-fluorouracil (5-FU) is a chemotherapeutic agent that is mainly metabolized by the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a DPYD single nucleotide polymorphism on 5-FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of DPYD in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into …


Strategies To Prevent Central Line-Associated Bloodstream Infections In Acute-Care Hospitals: 2022 Update, Niccolò Buetti, Jonas Marschall, Marci Drees, Mohamad G Fakih, Lynn Hadaway, Lisa L Maragakis, Elizabeth Monsees, Shannon Novosad, Naomi P O'Grady, Mark E Rupp, Joshua Wolf, Deborah Yokoe, Leonard A Mermel May 2022

Strategies To Prevent Central Line-Associated Bloodstream Infections In Acute-Care Hospitals: 2022 Update, Niccolò Buetti, Jonas Marschall, Marci Drees, Mohamad G Fakih, Lynn Hadaway, Lisa L Maragakis, Elizabeth Monsees, Shannon Novosad, Naomi P O'Grady, Mark E Rupp, Joshua Wolf, Deborah Yokoe, Leonard A Mermel

2020-Current year OA Pubs

No abstract provided.


American Society For Transplantation And Cellular Therapy Series: #5-Management Of Clostridioides Difficile Infection In Hematopoietic Cell Transplant Recipients, Carolyn D Alonso, Gabriela Maron, Mini Kamboj, Paul A Carpenter, Arun Gurunathan, Kathleen M Mullane, Erik R Dubberke May 2022

American Society For Transplantation And Cellular Therapy Series: #5-Management Of Clostridioides Difficile Infection In Hematopoietic Cell Transplant Recipients, Carolyn D Alonso, Gabriela Maron, Mini Kamboj, Paul A Carpenter, Arun Gurunathan, Kathleen M Mullane, Erik R Dubberke

2020-Current year OA Pubs

The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E …


Changes In Marriage, Divorce And Births During The Covid-19 Pandemic In Japan, Cyrus Ghaznavi, Takayuki Kawashima, Yuta Tanoue, Daisuke Yoneoka, Koji Makiyama, Haruka Sakamoto, Peter Ueda, Akifumi Eguchi, Shuhei Nomura May 2022

Changes In Marriage, Divorce And Births During The Covid-19 Pandemic In Japan, Cyrus Ghaznavi, Takayuki Kawashima, Yuta Tanoue, Daisuke Yoneoka, Koji Makiyama, Haruka Sakamoto, Peter Ueda, Akifumi Eguchi, Shuhei Nomura

Open Access Publications

INTRODUCTION: Marriage, divorce and fertility are declining in Japan. There is concern that the COVID-19 pandemic may have accelerated the decrease in marriages and births while increasing the number of divorces. Changes in partnership behaviours and fertility have significant implications for mental health, well-being and population demographics.

METHODS: Japanese vital statistical data were collected for December 2011-May 2021. We used the Farrington algorithm on the daily numbers of marriages, divorces and births (per month) in order to determine whether any given month between January 2017 and May 2021 had a significant excess or deficit. Analyses were conducted at the national …


Characterization Of A Novel Microfilarial Antigen For Diagnosis Of Wuchereria Bancrofti Infections, Sarah E. Greene, Kerstin Fischer, Young-Jun Choi, Kurt C. Curtis, Philip J. Budge, Makedonka Mitreva, Christopher L. King, Peter U. Fischer, Gary J. Weil May 2022

Characterization Of A Novel Microfilarial Antigen For Diagnosis Of Wuchereria Bancrofti Infections, Sarah E. Greene, Kerstin Fischer, Young-Jun Choi, Kurt C. Curtis, Philip J. Budge, Makedonka Mitreva, Christopher L. King, Peter U. Fischer, Gary J. Weil

Open Access Publications

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a …


Improving Eligibility Criteria For First-Line Trials For Patients With Dlbcl Using A Us-Based Delphi-Method Survey, R Andrew Harkins, Nancy L Bartlett, Amanda F Cashen, Brad S Kahl, Neha Mehta-Shah, Et Al Apr 2022

Improving Eligibility Criteria For First-Line Trials For Patients With Dlbcl Using A Us-Based Delphi-Method Survey, R Andrew Harkins, Nancy L Bartlett, Amanda F Cashen, Brad S Kahl, Neha Mehta-Shah, Et Al

Open Access Publications

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL …


Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al. Apr 2022

Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.


Longitudinal Dynamics Of Skin Bacterial Communities In The Context Of Staphylococcus Aureus Decolonization, Stephanie A Fritz, Todd N Wylie, Haley Gula, Patrick G Hogan, Mary G Boyle, Carol E Muenks, Melanie L Sullivan, Carey-Ann D Burnham, Kristine M Wylie Apr 2022

Longitudinal Dynamics Of Skin Bacterial Communities In The Context Of Staphylococcus Aureus Decolonization, Stephanie A Fritz, Todd N Wylie, Haley Gula, Patrick G Hogan, Mary G Boyle, Carol E Muenks, Melanie L Sullivan, Carey-Ann D Burnham, Kristine M Wylie

Open Access Publications

Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S. aureus skin and soft tissue infections (SSTI), skin swabs were collected from the anterior nares, axillae, and inguinal folds of 14 participants at 1- to 3-month intervals over 24 months. Four household members experienced SSTI during the first 12-months (observational period) and were prescribed a 5-day decolonization regimen with intranasal mupirocin and bleach water baths at the 12-month study visit. We sequenced the 16S …


Murine Respiratory Tract Infection With Classical Klebsiella Pneumoniae Induces Bronchus-Associated Lymphoid Tissue, Rachel K Wasbotten, Aubree A Dahler, Joseph J Mackel, Catherine Morffy Smith, David A Rosen Apr 2022

Murine Respiratory Tract Infection With Classical Klebsiella Pneumoniae Induces Bronchus-Associated Lymphoid Tissue, Rachel K Wasbotten, Aubree A Dahler, Joseph J Mackel, Catherine Morffy Smith, David A Rosen

Open Access Publications

Klebsiella pneumoniae is a Gram-negative, opportunistic pathogen that commonly causes nosocomial pneumonia, urinary tract infection, and septicemia. Our recent work utilizing a murine model of respiratory tract infection with classical K. pneumoniae demonstrated leukocyte aggregates in the lungs of mice at 28 days postinfection. Here, we sought to characterize the composition and development of these structures. Histopathological analyses of murine lungs revealed immune cell clusters surrounding the pulmonary vasculature and airways by 14 days postinfection, resembling inducible bronchus-associated lymphoid tissue (iBALT). Further investigation of these structures demonstrated central B cell aggregates with concomitant dispersed T cells. At day 28 postinfection, …


The Impact Of Implementing The Virtuo Blood Culture System On The Characteristics And Management Of Patients With Staphylococcus Aureus Bacteremia, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren Apr 2022

The Impact Of Implementing The Virtuo Blood Culture System On The Characteristics And Management Of Patients With Staphylococcus Aureus Bacteremia, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren

Open Access Publications

Persistent Staphylococcus aureus bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of S. aureus in patients with SAB. We performed a 24-month retrospective study of hospitalized adults with SAB and an infectious diseases consult comparing two time periods pre- (January to December 2018) and postimplementation (January to December 2019) in which the VersaTREK and BacT/Alert Virtuo blood culture systems were used, respectively. Measurements included SAB duration, time to positivity, source of bacteremia, antimicrobial therapy, and mortality. A total of 416 episodes of SAB occurred during the study period: 176 …


Persistent Methicillin-Susceptible Bacteremia Rapidly Cleared With Cefazolin And Ertapenem Combination Therapy In A Patient With Covid-19, Dan Ilges, Gayathri Krishnan, Elvin Geng Apr 2022

Persistent Methicillin-Susceptible Bacteremia Rapidly Cleared With Cefazolin And Ertapenem Combination Therapy In A Patient With Covid-19, Dan Ilges, Gayathri Krishnan, Elvin Geng

Open Access Publications

Methicillin-susceptible


Development And Validation Of The Rcos Prognostic Index: A Bedside Multivariable Logistic Regression Model To Predict Hypoxaemia Or Death In Patients With Sars-Cov-2 Infection, Gerardo Alvarez-Uria, Sumanth Gandra, Venkata R Gurram, Raghu P Reddy, Manoranjan Midde, Praveen Kumar, Ketty E Arce Apr 2022

Development And Validation Of The Rcos Prognostic Index: A Bedside Multivariable Logistic Regression Model To Predict Hypoxaemia Or Death In Patients With Sars-Cov-2 Infection, Gerardo Alvarez-Uria, Sumanth Gandra, Venkata R Gurram, Raghu P Reddy, Manoranjan Midde, Praveen Kumar, Ketty E Arce

Open Access Publications

Introduction: Previous COVID-19 prognostic models have been developed in hospital settings and are not applicable to COVID-19 cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 diagnosis.

Methods: The RDT COVID-19 Observational Study (RCOS) collected clinical data from patients with COVID-19 admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death.

Results: 4035 patients were included in the development …


Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al Apr 2022

Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al

Open Access Publications

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and …


Opportunities For Penicillin Allergy Evaluation In Dental Clinics, Amanda Vivo, Michael J. Durkin, Iboula Kale, Taylor Boyer, Margaret A. Fitzpatrick, Charlesnika T. Evans, Marianne M. Jurasic, Gretchen Gibson, Katie J. Suda Apr 2022

Opportunities For Penicillin Allergy Evaluation In Dental Clinics, Amanda Vivo, Michael J. Durkin, Iboula Kale, Taylor Boyer, Margaret A. Fitzpatrick, Charlesnika T. Evans, Marianne M. Jurasic, Gretchen Gibson, Katie J. Suda

Open Access Publications

No abstract provided.


Neutralizing Antibodies Protect Mice Against Venezuelan Equine Encephalitis Virus Aerosol Challenge, Natasha M Kafai, Soila Sukupolvi-Petty, Jaclyn Liu, Samantha Mackin, Arthur S Kim, Ana Jung, Lindsay Droit, Scott A Handley, Michael S Diamond, Et Al. Apr 2022

Neutralizing Antibodies Protect Mice Against Venezuelan Equine Encephalitis Virus Aerosol Challenge, Natasha M Kafai, Soila Sukupolvi-Petty, Jaclyn Liu, Samantha Mackin, Arthur S Kim, Ana Jung, Lindsay Droit, Scott A Handley, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may …


Uncertainty Analysis Of Chest X-Ray Lung Height Measurements And Size Matching For Lung Transplantation, Rodrigo Vazquez Guillamet, Maria C. Vazquez Guillamet, Ashraf Rjob, Andrew Bierhals, Irene Bello, Alberto Jauregui Abularach, Laneshia Tague, Michael Wallendorf, Gary F. Marklin, Chad Witt, Derek E. Byers, Daniel Kreisel, Ruben Nava, Varun Puri, Ramsey Hachem, Elbert P Trulock Apr 2022

Uncertainty Analysis Of Chest X-Ray Lung Height Measurements And Size Matching For Lung Transplantation, Rodrigo Vazquez Guillamet, Maria C. Vazquez Guillamet, Ashraf Rjob, Andrew Bierhals, Irene Bello, Alberto Jauregui Abularach, Laneshia Tague, Michael Wallendorf, Gary F. Marklin, Chad Witt, Derek E. Byers, Daniel Kreisel, Ruben Nava, Varun Puri, Ramsey Hachem, Elbert P Trulock

Open Access Publications

Background: Errors in measuring chest X-ray (CXR) lung heights could contribute to the occurrence of size-mismatched lung transplant procedures.

Methods: We first used Bland-Altman analysis for repeated measures to evaluate contributors to measurement error of chest X-ray lung height. We then applied error propagation theory to assess the impact of measurement error on size matching for lung transplantation.

Results: A total 387 chest X-rays from twenty-five donors and twenty-five recipients were measured by two raters. Individual standard deviation for lung height differences were independent of age, sex, donor

Conclusions: Individual chest X-ray lung heights are imprecise for the purpose of …


Fluvoxamine For Outpatient Management Of Covid-19 To Prevent Hospitalization: A Systematic Review And Meta-Analysis, Todd C Lee, Simone Vigod, Émilie Bortolussi-Courval, Ryan Hanula, David R Boulware, Eric J Lenze, Angela M Reiersen, Emily G Mcdonald Apr 2022

Fluvoxamine For Outpatient Management Of Covid-19 To Prevent Hospitalization: A Systematic Review And Meta-Analysis, Todd C Lee, Simone Vigod, Émilie Bortolussi-Courval, Ryan Hanula, David R Boulware, Eric J Lenze, Angela M Reiersen, Emily G Mcdonald

2020-Current year OA Pubs

Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization.

Objective: To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19.

Data Sources: World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov.

Study Selection: Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included.

Data Extraction and Synthesis: The PRISMA 2020 guidelines were followed and study details in terms of inclusion criteria, trial demographics, and the prespecified outcome of all-cause hospitalization were extracted. Risk of …


Suppressing Fatty Acid Synthase By Type I Interferon And Chemical Inhibitors As A Broad Spectrum Anti-Viral Strategy Against Sars-Cov-2, Saba R. Aliyari, Xiaochao Wei, Clay F. Semenkovich, Et Al. Apr 2022

Suppressing Fatty Acid Synthase By Type I Interferon And Chemical Inhibitors As A Broad Spectrum Anti-Viral Strategy Against Sars-Cov-2, Saba R. Aliyari, Xiaochao Wei, Clay F. Semenkovich, Et Al.

2020-Current year OA Pubs

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased …


Tumor-Associated Macrophages In Multiple Myeloma: Advances In Biology And Therapy, Jennifer Sun, Chaelee Park, Nicole Guenthner, Shannon Gurley, Luna Zhang, Berit Lubben, Ola Adebayo, Hannah Bash, Yixuan Chen, Mina Maksimos, Barbara Muz, Abdel Kareem Azab Apr 2022

Tumor-Associated Macrophages In Multiple Myeloma: Advances In Biology And Therapy, Jennifer Sun, Chaelee Park, Nicole Guenthner, Shannon Gurley, Luna Zhang, Berit Lubben, Ola Adebayo, Hannah Bash, Yixuan Chen, Mina Maksimos, Barbara Muz, Abdel Kareem Azab

Open Access Publications

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematological malignancy in the world. The MM tumor microenvironment (TME) within the BM niche consists of a wide range of elements which play important roles in supporting MM disease progression, survival, proliferation, angiogenesis, as well as drug resistance. Together, the TME fosters an immunosuppressive environment in which immune recognition and response are repressed. Macrophages are a central player in the immune system with diverse functions, and it has been long established that macrophages play a critical role in both inducing …


Structural And Molecular Rationale For The Diversification Of Resistance Mediated By The Antibiotic_Nat Family, Peter J Stogios, Emily Bordeleau, Zhiyu Xu, Tatiana Skarina, Elena Evdokimova, Sommer Chou, Luke Diorio-Toth, Alaric W D'Souza, Sanket Patel, Gautam Dantas, Gerard D Wright, Alexei Savchenko Mar 2022

Structural And Molecular Rationale For The Diversification Of Resistance Mediated By The Antibiotic_Nat Family, Peter J Stogios, Emily Bordeleau, Zhiyu Xu, Tatiana Skarina, Elena Evdokimova, Sommer Chou, Luke Diorio-Toth, Alaric W D'Souza, Sanket Patel, Gautam Dantas, Gerard D Wright, Alexei Savchenko

Open Access Publications

The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical …


Predictors Of Humoral Response To Sars-Cov-2 Mrna Vaccine Bnt162b2 In Patients Receiving Maintenance Dialysis, Li Tingting, Sumanth Gandra, Kimberly A. Reske, Margaret A. Olsen, Silvana Bommarito, Candace Miller, Karl G. Hock, Claire A. Ballman, Christina Su, Na Le Dang, Jennie H. Kwon, David K. Warren, Victoria J. Fraser, Christopher W. Farnsworth Mar 2022

Predictors Of Humoral Response To Sars-Cov-2 Mrna Vaccine Bnt162b2 In Patients Receiving Maintenance Dialysis, Li Tingting, Sumanth Gandra, Kimberly A. Reske, Margaret A. Olsen, Silvana Bommarito, Candace Miller, Karl G. Hock, Claire A. Ballman, Christina Su, Na Le Dang, Jennie H. Kwon, David K. Warren, Victoria J. Fraser, Christopher W. Farnsworth

Open Access Publications

No abstract provided.


Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho Mar 2022

Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho

Open Access Publications

OBJECTIVES: In Uganda, infection-related cancers have made the greatest contribution to cancer burden in the past; however, burden from lifestyle-related cancers has increased recently. Using the Kampala Cancer Registry data, we projected incidence of top five cancers, namely, Kaposi sarcoma (KS), cervical, breast and prostate cancer, and non-Hodgkin's lymphoma (NHL) in Uganda.

DESIGN: Trend analysis of cancer registry data.

SETTING: Kampala Cancer Registry, Uganda.

MAIN OUTCOME MEASURE: Cancer incidence data from 2001 to 2015 were used and projected to 2030. Population data were obtained from the Uganda Bureau of Statistics. Age-standardised incidence rates (ASRs) and their trends over the observed …


Metronidazole Treatment Rapidly Reduces Genital Inflammation Through Effects On Bacterial Vaginosis-Associated Bacteria Rather Than Lactobacilli, Eric Armstrong, Hilary Reno, Et Al. Mar 2022

Metronidazole Treatment Rapidly Reduces Genital Inflammation Through Effects On Bacterial Vaginosis-Associated Bacteria Rather Than Lactobacilli, Eric Armstrong, Hilary Reno, Et Al.

2020-Current year OA Pubs

BackgroundBacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this reduction is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species.METHODSTo evaluate the short-term effect of standard BV treatment on genital immunology and the vaginal microbiota, vaginal swabs were collected immediately before and after metronidazole treatment for BV and analyzed with multiplex ELISA, metagenomic sequencing, and quantitative PCR.RESULTSTopical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, …


Durable Reduction Of Clostridioides Difficile Infection Recurrence And Microbiome Restoration After Treatment With Rbx2660: Results From An Open-Label Phase 2 Clinical Trial, Robert Orenstein, Erik R Dubberke, Sahil Khanna, Christine H Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L Dupont, Dale N Gerding, Ken F Blount, Sarah Mische, Adam Harvey Mar 2022

Durable Reduction Of Clostridioides Difficile Infection Recurrence And Microbiome Restoration After Treatment With Rbx2660: Results From An Open-Label Phase 2 Clinical Trial, Robert Orenstein, Erik R Dubberke, Sahil Khanna, Christine H Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L Dupont, Dale N Gerding, Ken F Blount, Sarah Mische, Adam Harvey

2020-Current year OA Pubs

BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.

METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered …


Air Exchanges, Climate Change, And Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2): Results From A Survey Of The Society Of Healthcare Epidemiology Of America Research Network (Srn), Jason P. Burnham, Fred Betz, Roger Lautz, Ehsan Mousavi, Richard A. Martinello, Forbes Mcgain, Jodi D. Sherman Mar 2022

Air Exchanges, Climate Change, And Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2): Results From A Survey Of The Society Of Healthcare Epidemiology Of America Research Network (Srn), Jason P. Burnham, Fred Betz, Roger Lautz, Ehsan Mousavi, Richard A. Martinello, Forbes Mcgain, Jodi D. Sherman

Open Access Publications

No abstract provided.


Numbers And Narratives: How Qualitative Methods Can Strengthen The Science Of Paediatric Antimicrobial Stewardship, Charlotte Z Woods-Hill, Anping Xie, John Lin, Heather A Wolfe, Alex S Plattner, Sara Malone, Kathleen Chiotos, Julia E Szymczak Mar 2022

Numbers And Narratives: How Qualitative Methods Can Strengthen The Science Of Paediatric Antimicrobial Stewardship, Charlotte Z Woods-Hill, Anping Xie, John Lin, Heather A Wolfe, Alex S Plattner, Sara Malone, Kathleen Chiotos, Julia E Szymczak

2020-Current year OA Pubs

Antimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance …