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Position Paper: Models Of Post-Transplant Care For Individuals With Cystic Fibrosis, Edward Mckone, Joshua Blatter, Ramsey Hachem, Et Al. May 2023

Position Paper: Models Of Post-Transplant Care For Individuals With Cystic Fibrosis, Edward Mckone, Joshua Blatter, Ramsey Hachem, Et Al.

2020-Current year OA Pubs

There is no consensus on the best model of care for individuals with CF to manage the non-pulmonary complications that persist after lung transplant. The CF Foundation virtually convened a group of international experts in CF and lung-transplant care. The committee reviewed literature and shared the post-lung transplant model of care practiced by their programs. The committee then developed a survey that was distributed internationally to both the clinical and individual with CF/family audiences to determine the strengths, weaknesses, and preferences for various models of transplant care. Discussion generated two models to accomplish optimal CF care after transplant. The first …


Remote Global Radiation Oncology Education And Training: A Pathway To Increase Access To High-Quality Radiation Therapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Matthew Schmidt, Tianyu Zhao, Hiram Gay, Jeff Michalski, Geoffrey Hugo, Jacaranda Van Rheenen, Baozhou Sun, Et Al. May 2023

Remote Global Radiation Oncology Education And Training: A Pathway To Increase Access To High-Quality Radiation Therapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Matthew Schmidt, Tianyu Zhao, Hiram Gay, Jeff Michalski, Geoffrey Hugo, Jacaranda Van Rheenen, Baozhou Sun, Et Al.

2020-Current year OA Pubs

PURPOSE: There is a vital need to train radiation therapy professionals in low- and middle-income countries (LMICs) to develop sustainable cancer treatment capacity and infrastructure. LMICs have started to introduce intensity modulated radiation therapy (IMRT), which is the standard of care in high-income countries, because of improved outcomes and reduced toxicities. This work reports the efficacy of a complementary asynchronous plus synchronous virtual-training approach on improving radiation therapy professions' self-confidence levels and evaluating participants' attitudes toward asynchronous and synchronous didactic hands-on learning in 3 LMICs.

METHODS AND MATERIALS: Training was provided to 37 participants from Uganda, Guatemala, and Mongolia, which …


Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala May 2023

Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

PURPOSE: Economic empowerment and family strengthening interventions have shown promise for improving psychosocial well-being in a range of populations. This study investigates the effect of a combination economic and family strengthening intervention on psychosocial well-being among Ugandan adolescent girls and young women (AGYW).

METHODS: We harnessed data from a three-arm cluster randomized controlled trial among AGYW aged 14-17 years in 47 Ugandan secondary schools. Schools were randomized to either a youth development account intervention (YDA) [N = 16 schools], YDA plus a multiple family group intervention (YDA + MFG) [N = 15 schools], or bolstered standard of care (BSOC) [N …


Polygenic Risk Score Penetrance & Recurrence Risk In Familial Alzheimer Disease, Min Qiao, Carlos Cruchaga, Et Al. May 2023

Polygenic Risk Score Penetrance & Recurrence Risk In Familial Alzheimer Disease, Min Qiao, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease.

METHODS: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE-ε4 carriers …


Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al. May 2023

Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD

PURPOSE: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.

METHODS: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.

RESULTS: In a subset of the dataset aligned …


Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski May 2023

Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski

2020-Current year OA Pubs

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric …


Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa May 2023

Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa

2020-Current year OA Pubs

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year.

OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery.

STUDY DESIGN: The Medicare 5% Limited Data Set was queried from …


Biochemical Network Analysis Of Protein-Protein Interactions To Follow-Up T1 Bladder Cancer Patients, Luís B Carvalho, José Luis Capelo Martínez, Carlos Lodeiro, Rafael Bento, Rajiv Dhir, Jeremiah J Morrissey, Luis Campos Pinheiro, Mariana Medeiros, Hugo M Santos Apr 2023

Biochemical Network Analysis Of Protein-Protein Interactions To Follow-Up T1 Bladder Cancer Patients, Luís B Carvalho, José Luis Capelo Martínez, Carlos Lodeiro, Rafael Bento, Rajiv Dhir, Jeremiah J Morrissey, Luis Campos Pinheiro, Mariana Medeiros, Hugo M Santos

2020-Current year OA Pubs

Bladder cancer (BCa) is a prevalent disease with a high risk of aggressive recurrence in T1-stage patients. Despite the efforts to anticipate recurrence, a reliable method has yet to be developed. In this work, we employed high-resolution mass spectrometry to compare the urinary proteome of T1-stage BCa patients with recurring versus non-recurring disease to uncover actionable clinical information predicting recurrence. All patients were diagnosed with T1-stage bladder cancer between the ages of 51 and 91, and urine samples were collected before medical intervention. Our results suggest that the urinary myeloperoxidase to cubilin ratio could be used as a new tool …


Mzion Enables Deep And Precise Identification Of Peptides In Data-Dependent Acquisition Proteomics, Qiang Zhang Apr 2023

Mzion Enables Deep And Precise Identification Of Peptides In Data-Dependent Acquisition Proteomics, Qiang Zhang

2020-Current year OA Pubs

Sensitive and reliable identification of proteins and peptides pertains the basis of proteomics. We introduce Mzion, a new database search tool for data-dependent acquisition (DDA) proteomics. Our tool utilizes an intensity tally strategy and achieves generally a higher performance in terms of depth and precision across 20 datasets, ranging from large-scale to single-cell proteomics. Compared to several other search engines, Mzion matches on average 20% more peptide spectra at tryptic enzymatic specificity and 80% more at no enzymatic specificity from six large-scale, global datasets. Mzion also identifies more phosphopeptide spectra that can be explained by fewer proteins, demonstrated by six …


Utilizing Computed Tomography Volumetry For Size Matching Prior To Lung Transplantation: A Case Series, Hailey M. Shepherd, Khashayar Farahnak, M. Shea Harrison, C. Corbin Frye, Gary F. Marklin, Andrew J. Bierhals, Ramsey R. Hachem, Chad A. Witt, Rodrigo V. Guillamet, Derek E. Byers, Benjamin D. Kozower, Bryan F. Meyers, Ruben G. Nava, G. Alexander Patterson, Daniel Kreisel, Varun Puri Apr 2023

Utilizing Computed Tomography Volumetry For Size Matching Prior To Lung Transplantation: A Case Series, Hailey M. Shepherd, Khashayar Farahnak, M. Shea Harrison, C. Corbin Frye, Gary F. Marklin, Andrew J. Bierhals, Ramsey R. Hachem, Chad A. Witt, Rodrigo V. Guillamet, Derek E. Byers, Benjamin D. Kozower, Bryan F. Meyers, Ruben G. Nava, G. Alexander Patterson, Daniel Kreisel, Varun Puri

2020-Current year OA Pubs

BACKGROUND: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value.

CASE DESCRIPTION: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly …


Metagenomic Analysis Of Dna Viruses With Targeted Sequence Capture Of Canine Lobular Orbital Adenomas And Normal Conjunctiva, Elizabeth A F Schaefer, Shirley Chu, Kristine M Wylie, Todd N Wylie, Obi L Griffith, Jacqueline W Pearce, Gayle C Johnson, Jeffrey N Bryan, Brian K Flesner Apr 2023

Metagenomic Analysis Of Dna Viruses With Targeted Sequence Capture Of Canine Lobular Orbital Adenomas And Normal Conjunctiva, Elizabeth A F Schaefer, Shirley Chu, Kristine M Wylie, Todd N Wylie, Obi L Griffith, Jacqueline W Pearce, Gayle C Johnson, Jeffrey N Bryan, Brian K Flesner

2020-Current year OA Pubs

Our study aims are: (1) to evaluate phenotypically normal canine conjunctival and orbital tissue and tissue from canine lobular orbital adenomas (CLOAs) for the presence of viral genomic material and (2) phylogenetically classify detected DNA viruses to determine if a DNA virus is associated with CLOAs. A total of 31 formalin fixed paraffin embedded CLOA tissue samples, 4 papillomas or sarcoid, and 10 fresh clinically normal conjunctival tissues were included in this study. Genomic DNA was isolated from all samples and sequencing libraries were prepared. The libraries were molecularly indexed and pooled and viral DNA was enriched via targeted sequence …


The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S Weinstock, C Charles Gu, Et Al. Apr 2023

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S Weinstock, C Charles Gu, Et Al.

2020-Current year OA Pubs

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …


Definitive Chemoradiation Associated With Improved Survival Outcomes In Patients With Synchronous Oligometastatic Esophageal Cancer, Thomas Matoska, Anjishnu Banerjee, Aditya Shreenivas, Lauren Jurkowski, Monica E Shukla, Elizabeth M Gore, Paul Linsky, Mario Gasparri, Ben George, Candice Johnstone, David Johnstone, Lindsay L Puckett Apr 2023

Definitive Chemoradiation Associated With Improved Survival Outcomes In Patients With Synchronous Oligometastatic Esophageal Cancer, Thomas Matoska, Anjishnu Banerjee, Aditya Shreenivas, Lauren Jurkowski, Monica E Shukla, Elizabeth M Gore, Paul Linsky, Mario Gasparri, Ben George, Candice Johnstone, David Johnstone, Lindsay L Puckett

2020-Current year OA Pubs

BACKGROUND: The study of oligometastatic esophageal cancer (EC) is relatively new. Preliminary data suggests that more aggressive treatment regimens in select patients may improve survival rates in oligometastatic EC. However, the consensus recommends palliative treatment. We hypothesized that oligometastatic esophageal cancer patients treated with a definitive approach (chemoradiotherapy [CRT]) would have improved overall survival (OS) compared to those treated with a purely palliative intent and historical controls.

METHODS: Patients diagnosed with synchronous oligometastatic (any histology, ≤5 metastatic foci) esophageal cancer treated in a single academic hospital were retrospectively analyzed and divided into definitive and palliative treatment groups. Definitive CRT was …


Ebolavirus Species-Specific Interferon Antagonism Mediated By Vp24, Palaniappan Ramanathan, Bersabeh Tigabu, Rodrigo I Santos, Philipp A Ilinykh, Natalia Kuzmina, Olivia A Vogel, Naveen Thakur, Hamza Ahmed, Chao Wu, Gaya K Amarasinghe, Christopher F Basler, Alexander Bukreyev Apr 2023

Ebolavirus Species-Specific Interferon Antagonism Mediated By Vp24, Palaniappan Ramanathan, Bersabeh Tigabu, Rodrigo I Santos, Philipp A Ilinykh, Natalia Kuzmina, Olivia A Vogel, Naveen Thakur, Hamza Ahmed, Chao Wu, Gaya K Amarasinghe, Christopher F Basler, Alexander Bukreyev

2020-Current year OA Pubs

Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic, and Reston (RESTV) is not known to cause a disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously, we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with a reduced inhibition in IFN-I signaling. We hypothesized that modification of eVP24-karyopherin …


Benchmarking Hospital Practices And Policies On Intrahospital Neurocritical Care Transport: The Safe-Neuro-Transport Study, Kapil G Zirpe, Bhunyawee Alunpipatthanachai, Nassim Matin, Bernice G Gulek, Patricia A Blissitt, Katherine Palmieri, Kathryn Rosenblatt, Umeshkumar Athiraman, Suneeta Gollapudy, Marie Angele Theard, Sarah Wahlster, Monica S Vavilala, Abhijit V Lele, Safe-Neuro-Transport Collaborators Apr 2023

Benchmarking Hospital Practices And Policies On Intrahospital Neurocritical Care Transport: The Safe-Neuro-Transport Study, Kapil G Zirpe, Bhunyawee Alunpipatthanachai, Nassim Matin, Bernice G Gulek, Patricia A Blissitt, Katherine Palmieri, Kathryn Rosenblatt, Umeshkumar Athiraman, Suneeta Gollapudy, Marie Angele Theard, Sarah Wahlster, Monica S Vavilala, Abhijit V Lele, Safe-Neuro-Transport Collaborators

2020-Current year OA Pubs

An electronic survey was administered to multidisciplinary neurocritical care providers at 365 hospitals in 32 countries to describe intrahospital transport (IHT) practices of neurocritically ill patients at their institutions. The reported IHT practices were stratified by World Bank country income level. Variability between high-income (HIC) and low/middle-income (LMIC) groups, as well as variability between hospitals within countries, were expressed as counts/percentages and intracluster correlation coefficients (ICCs) with a 95% confidence interval (CI). A total of 246 hospitals (67% response rate;


Abrogation Of Map4k4 Protein Function Causes Congenital Anomalies In Humans And Zebrafish, Victoria Patterson, Dorothy K Grange, Et Al. Apr 2023

Abrogation Of Map4k4 Protein Function Causes Congenital Anomalies In Humans And Zebrafish, Victoria Patterson, Dorothy K Grange, Et Al.

2020-Current year OA Pubs

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in


3d Printing Exposure And Perception In Radiology Residency: Survey Results Of Radiology Chief Residents, David Chen, Aravinda Ganapathy, Nihil Abraham, Kaitlin M Marquis, Grace L Bishop, Frank J Rybicki, Mark J Hoegger, David H Ballard Apr 2023

3d Printing Exposure And Perception In Radiology Residency: Survey Results Of Radiology Chief Residents, David Chen, Aravinda Ganapathy, Nihil Abraham, Kaitlin M Marquis, Grace L Bishop, Frank J Rybicki, Mark J Hoegger, David H Ballard

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: The purpose of this study is to summarize a survey of radiology chief residents focused on 3D printing in radiology.

MATERIALS AND METHODS: An online survey was distributed to chief residents in North American radiology residencies by subgroups of the Association of University Radiologists. The survey included a subset of questions focused on the clinical use of 3D printing and perceptions of the role of 3D printing and radiology. Respondents were asked to define the role of 3D printing at their institution and asked about the potential role of clinical 3D printing in radiology and radiology residencies. …


Cueing Natural Event Boundaries Improves Memory In People With Post-Traumatic Stress Disorder, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks Apr 2023

Cueing Natural Event Boundaries Improves Memory In People With Post-Traumatic Stress Disorder, Barbara L Pitts, Michelle L Eisenberg, Heather R Bailey, Jeffrey M Zacks

2020-Current year OA Pubs

People with post-traumatic stress disorder (PTSD) often report difficulty remembering information in their everyday lives. Recent findings suggest that such difficulties may be due to PTSD-related deficits in parsing ongoing activity into discrete events, a process called event segmentation. Here, we investigated the causal relationship between event segmentation and memory by cueing event boundaries and evaluating its effect on subsequent memory in people with PTSD. People with PTSD (n = 38) and trauma-matched controls (n = 36) watched and remembered videos of everyday activities that were either unedited, contained visual and auditory cues at event boundaries, or contained visual and …


Eliciting Opinions On Health Messaging During The Covid-19 Pandemic: Qualitative Survey Study, Sienna Ruiz, Uzoma Charles Okere, Michelle Eggers, Catina O'Leary, Mary Politi, Fei Wan, Ashley J Housten Apr 2023

Eliciting Opinions On Health Messaging During The Covid-19 Pandemic: Qualitative Survey Study, Sienna Ruiz, Uzoma Charles Okere, Michelle Eggers, Catina O'Leary, Mary Politi, Fei Wan, Ashley J Housten

2020-Current year OA Pubs

BACKGROUND: Effective public health messaging has been necessary throughout the COVID-19 pandemic, but stakeholders have struggled to communicate critical information to the public, especially in different types of locations such as urban and rural areas.

OBJECTIVE: This study aimed to identify opportunities to improve COVID-19 messages for community distribution in rural and urban settings and to summarize the findings to inform future messaging.

METHODS: We purposively sampled by region (urban or rural) and participant type (general public or health care professional) to survey participants about their opinions on 4 COVID-19 health messages. We designed open-ended survey questions and analyzed the …


Large Multi-Ethnic Genetic Analyses Of Amyloid Imaging Identify New Genes For Alzheimer Disease, Muhammad Ali, Priyanka Gorijala, Daniel Western, Jigyasha Timsina, Maria V Fernández, Gengsheng Chen, Brian Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Eric Mcdade, Yun Ju Sung, Carlos Cruchaga, Et Al. Apr 2023

Large Multi-Ethnic Genetic Analyses Of Amyloid Imaging Identify New Genes For Alzheimer Disease, Muhammad Ali, Priyanka Gorijala, Daniel Western, Jigyasha Timsina, Maria V Fernández, Gengsheng Chen, Brian Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Eric Mcdade, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10


Inulin Diet Uncovers Complex Diet-Microbiota-Immune Cell Interactions Remodeling The Gut Epithelium, Renan Oliveira Corrêa, José Luís Fachi, Marco Colonna, Et Al. Apr 2023

Inulin Diet Uncovers Complex Diet-Microbiota-Immune Cell Interactions Remodeling The Gut Epithelium, Renan Oliveira Corrêa, José Luís Fachi, Marco Colonna, Et Al.

2020-Current year OA Pubs

BACKGROUND: The continuous proliferation of intestinal stem cells followed by their tightly regulated differentiation to epithelial cells is essential for the maintenance of the gut epithelial barrier and its functions. How these processes are tuned by diet and gut microbiome is an important, but poorly understood question. Dietary soluble fibers, such as inulin, are known for their ability to impact the gut bacterial community and gut epithelium, and their consumption has been usually associated with health improvement in mice and humans. In this study, we tested the hypothesis that inulin consumption modifies the composition of colonic bacteria and this impacts …


Valoctocogene Roxaparvovec Gene Transfer In Participants With Hiv, Margaret V Ragni, Elaine Majerus, Sylvia Fong, Bridget Yates, Stephen Scheeler, Lisa Razon, Hua Yu, Divya B Reddy, Tara M Robinson Apr 2023

Valoctocogene Roxaparvovec Gene Transfer In Participants With Hiv, Margaret V Ragni, Elaine Majerus, Sylvia Fong, Bridget Yates, Stephen Scheeler, Lisa Razon, Hua Yu, Divya B Reddy, Tara M Robinson

2020-Current year OA Pubs

No abstract provided.


Mrgpra3-Expressing Pruriceptors Drive Pruritogen-Induced Alloknesis Through Mechanosensitive Piezo2 Channel, Ping Lu, Yonghui Zhao, Zili Xie, Huan Zhou, Xinzhong Dong, Gregory F Wu, Brian S Kim, Jing Feng, Hongzhen Hu Apr 2023

Mrgpra3-Expressing Pruriceptors Drive Pruritogen-Induced Alloknesis Through Mechanosensitive Piezo2 Channel, Ping Lu, Yonghui Zhao, Zili Xie, Huan Zhou, Xinzhong Dong, Gregory F Wu, Brian S Kim, Jing Feng, Hongzhen Hu

2020-Current year OA Pubs

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, …


Activation Of The Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated By Plasmepsin X Destruction Of The Prodomain, Sumit Mukherjee, Armiyaw S. Nasamu, Kelly C. Rubiano, Daniel E. Goldberg Apr 2023

Activation Of The Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated By Plasmepsin X Destruction Of The Prodomain, Sumit Mukherjee, Armiyaw S. Nasamu, Kelly C. Rubiano, Daniel E. Goldberg

2020-Current year OA Pubs

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated …


Molnupiravir And Risk Of Post-Acute Sequelae Of Covid-19: Cohort Study, Yan Xie, Taeyoung Choi, Ziyad Al-Aly Apr 2023

Molnupiravir And Risk Of Post-Acute Sequelae Of Covid-19: Cohort Study, Yan Xie, Taeyoung Choi, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVE: To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.

DESIGN: Cohort study.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or …


Nk Cell-Derived Extracellular Granzyme B Drives Epithelial Ulceration During Hsv-2 Genital Infection, Ying Shiang Lim, Aisha G Lee, Xiaoping Jiang, Jason M Scott, Adjoa Cofie, Sandeep Kumar, Dania Kennedy, David J Granville, Haina Shin Apr 2023

Nk Cell-Derived Extracellular Granzyme B Drives Epithelial Ulceration During Hsv-2 Genital Infection, Ying Shiang Lim, Aisha G Lee, Xiaoping Jiang, Jason M Scott, Adjoa Cofie, Sandeep Kumar, Dania Kennedy, David J Granville, Haina Shin

2020-Current year OA Pubs

Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model of vaginal herpes simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation of the serine protease granzyme B in the vagina, coinciding with vaginal epithelial ulceration. Genetic loss of granzyme B or therapeutic inhibition by a specific protease inhibitor reduces disease and restores epithelial integrity without altering viral control. Distinct effects of granzyme B and perforin deficiency on pathology indicates that granzyme B acts independent of its classic …


Site-1 Protease Inhibits Mitochondrial Respiration By Controlling The Tgf-Β Target Gene Mss51, Muhammad G Mousa, Lahari Vuppaladhadiam, Meredith O Kelly, Terri Pietka, Shelby Ek, Karen C Shen, Gretchen A Meyer, Brian N Finck, Rita T Brookheart Apr 2023

Site-1 Protease Inhibits Mitochondrial Respiration By Controlling The Tgf-Β Target Gene Mss51, Muhammad G Mousa, Lahari Vuppaladhadiam, Meredith O Kelly, Terri Pietka, Shelby Ek, Karen C Shen, Gretchen A Meyer, Brian N Finck, Rita T Brookheart

2020-Current year OA Pubs

The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P …


Transcriptomic Atlas And Interaction Networks Of Brain Cells In Mouse Cns Demyelination And Remyelination, Jinchao Hou, Yingyue Zhou, Zhangying Cai, Marina Terekhova, Amanda Swain, Prabhakar S Andhey, Rafaela M Guimaraes, Alina Ulezko Antonova, Tian Qiu, Sanja Sviben, Gregory Strout, James A J Fitzpatrick, Yun Chen, Susan Gilfillan, Do-Hyun Kim, Steven J Van Dyken, Maxim N Artyomov, Marco Colonna Apr 2023

Transcriptomic Atlas And Interaction Networks Of Brain Cells In Mouse Cns Demyelination And Remyelination, Jinchao Hou, Yingyue Zhou, Zhangying Cai, Marina Terekhova, Amanda Swain, Prabhakar S Andhey, Rafaela M Guimaraes, Alina Ulezko Antonova, Tian Qiu, Sanja Sviben, Gregory Strout, James A J Fitzpatrick, Yun Chen, Susan Gilfillan, Do-Hyun Kim, Steven J Van Dyken, Maxim N Artyomov, Marco Colonna

2020-Current year OA Pubs

Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFB


Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz Apr 2023

Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased …


Advances In Mass Spectrometry On Membrane Proteins, Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L Gross Apr 2023

Advances In Mass Spectrometry On Membrane Proteins, Hsin-Chieh Yang, Weikai Li, Jie Sun, Michael L Gross

2020-Current year OA Pubs

Understanding the higher-order structure of membrane proteins (MPs), which are vital for numerous biological processes, is crucial for comprehending their function. Although several biophysical approaches have been used to study the structure of MPs, limitations exist owing to the proteins' dynamic nature and heterogeneity. Mass spectrometry (MS) is emerging as a powerful tool for investigating membrane protein structure and dynamics. Studying MPs using MS, however, must meet several challenges including the lack of stability and solubility of MPs, the complexity of the protein-membrane system, and the difficulty of digestion and detection. To meet these challenges, recent advances in MS have …