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Full-Text Articles in Internal Medicine

Comprehensive Analysis Of Bulk And Single-Cell Transcriptomic Data Reveals A Novel Signature Associated With Endoplasmic Reticulum Stress, Lipid Metabolism, And Liver Metastasis In Pancreatic Cancer, Xiaohong Liu, Bo Ren, Yuan Fang, Jie Ren, Xing Wang, Minzhi Gu, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao Apr 2024

Comprehensive Analysis Of Bulk And Single-Cell Transcriptomic Data Reveals A Novel Signature Associated With Endoplasmic Reticulum Stress, Lipid Metabolism, And Liver Metastasis In Pancreatic Cancer, Xiaohong Liu, Bo Ren, Yuan Fang, Jie Ren, Xing Wang, Minzhi Gu, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy.

METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO …


Prognostic Values Of Serum Lactate-To-Bicarbonate Ratio And Lactate For Predicting 28-Day In-Hospital Mortality In Children With Dengue Shock Syndrome, Thanh Nguyen Tat, Nhu Vo Hoang-Thien, Dat Nguyen Tat, Phuc Hoang Nguyen, Lien Thi Ho, Duong Hung Doan, Dung Tuan Phan, Yen Nguyen-Hoang Duong, Truc Huynh Nguyen, Tuyet Kim Nguyen, Ha Thi-Thu Dinh, Thuy Thi-Diem Dinh, Anh Thi-Mai Pham, Viet Do Chau, Tung Huu Trinh, Luan Vo Thanh Apr 2024

Prognostic Values Of Serum Lactate-To-Bicarbonate Ratio And Lactate For Predicting 28-Day In-Hospital Mortality In Children With Dengue Shock Syndrome, Thanh Nguyen Tat, Nhu Vo Hoang-Thien, Dat Nguyen Tat, Phuc Hoang Nguyen, Lien Thi Ho, Duong Hung Doan, Dung Tuan Phan, Yen Nguyen-Hoang Duong, Truc Huynh Nguyen, Tuyet Kim Nguyen, Ha Thi-Thu Dinh, Thuy Thi-Diem Dinh, Anh Thi-Mai Pham, Viet Do Chau, Tung Huu Trinh, Luan Vo Thanh

Faculty, Staff and Student Publications

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of …


Inaccurate Diagnosis Of Diabetes Type In Youth: Prevalence, Characteristics, And Implications, Mustafa Tosur, Xiaofan Huang, Audrey S Inglis, Rebecca Schneider Aguirre, Maria J Redondo Apr 2024

Inaccurate Diagnosis Of Diabetes Type In Youth: Prevalence, Characteristics, And Implications, Mustafa Tosur, Xiaofan Huang, Audrey S Inglis, Rebecca Schneider Aguirre, Maria J Redondo

Faculty, Staff and Students Publications

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), …


Emerging Variants Develop Total Escape From Potent Monoclonal Antibodies Induced By Ba4/5 Infection, Chang Liu, Raksha Das, Aiste Dijokaite-Guraliuc, Daming Zhou, Alexander J Mentzer, Piyada Supasa, Muneeswaran Selvaraj, Helen M E Duyvesteyn, Thomas G Ritter, Nigel Temperton, Paul Klenerman, Susanna J Dunachie, Neil G Paterson, Mark A Williams, David R Hall, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton Apr 2024

Emerging Variants Develop Total Escape From Potent Monoclonal Antibodies Induced By Ba4/5 Infection, Chang Liu, Raksha Das, Aiste Dijokaite-Guraliuc, Daming Zhou, Alexander J Mentzer, Piyada Supasa, Muneeswaran Selvaraj, Helen M E Duyvesteyn, Thomas G Ritter, Nigel Temperton, Paul Klenerman, Susanna J Dunachie, Neil G Paterson, Mark A Williams, David R Hall, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of …


Refractory Chronic Spontaneous Urticaria After Heterologous Covid-19 Booster Vaccination, Miranda Crista Tomaras, Leah Michelle Douglas, Rosa Michelle Schmidt, Maria Suzanne Bloomquist, Abdul Hafeez Diwan, Soo Jung Kim Apr 2024

Refractory Chronic Spontaneous Urticaria After Heterologous Covid-19 Booster Vaccination, Miranda Crista Tomaras, Leah Michelle Douglas, Rosa Michelle Schmidt, Maria Suzanne Bloomquist, Abdul Hafeez Diwan, Soo Jung Kim

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) involves recurrent, pruritic wheals lasting more than 6 weeks in response to various etiologies, including unknown causality. Though most cutaneous reactions to the COVID-19 vaccine series are self-limited and of short duration, more complex presentations including chronic spontaneous urticaria have been described. To the best of our knowledge, this is the first report of chronic spontaneous urticaria following heterologous mRNA COVID-19 booster vaccination that includes vaccination with both forms of the mRNA vaccine. Our patient received Pfizer-BioNTech for the primary series and Moderna for the booster. After failing several therapies, our patient's urticaria was refractory even …


A Digital Twin Of The Infant Microbiome To Predict Neurodevelopmental Deficits., Nicholas Sizemore, Kaitlyn Oliphant, Ruolin Zheng, Camilia R Martin, Erika C Claud, Ishanu Chattopadhyay Apr 2024

A Digital Twin Of The Infant Microbiome To Predict Neurodevelopmental Deficits., Nicholas Sizemore, Kaitlyn Oliphant, Ruolin Zheng, Camilia R Martin, Erika C Claud, Ishanu Chattopadhyay

Internal Medicine Faculty Publications

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R2 = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (Mδ) and identify infants …


Non-Traumatic Osteonecrosis Of The Femoral Head Induced By Steroid And Alcohol Exposure Is Associated With Intestinal Flora Alterations And Metabolomic Profiles, Qing-Yuan Zheng, Ye Tao, Lei Geng, Peng Ren, Ming Ni, Guo-Qiang Zhang Apr 2024

Non-Traumatic Osteonecrosis Of The Femoral Head Induced By Steroid And Alcohol Exposure Is Associated With Intestinal Flora Alterations And Metabolomic Profiles, Qing-Yuan Zheng, Ye Tao, Lei Geng, Peng Ren, Ming Ni, Guo-Qiang Zhang

Faculty, Staff and Student Publications

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives.

METHODS: …


Storylines Of Family Medicine Xii: Family Medicine And The Healthcare System, William B Ventres, Leslie A Stone, Jeannette E South-Paul, Kendall M Campbell, Aerial R Petty, Hima Ekanadham, Kurt C Stange, Rebecca S Etz, William L Miller, Robert L Ferrer, Marianna Kong, Thomas Bodenheimer, Roger Strasser, Sharon C M Reece, Joshua Freeman, John M Westfall Apr 2024

Storylines Of Family Medicine Xii: Family Medicine And The Healthcare System, William B Ventres, Leslie A Stone, Jeannette E South-Paul, Kendall M Campbell, Aerial R Petty, Hima Ekanadham, Kurt C Stange, Rebecca S Etz, William L Miller, Robert L Ferrer, Marianna Kong, Thomas Bodenheimer, Roger Strasser, Sharon C M Reece, Joshua Freeman, John M Westfall

Faculty, Staff and Students Publications

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In ‘XII: Family medicine and the future of the healthcare system’, authors address the following themes: ‘Leadership in family medicine’, ‘Becoming an academic family physician’, ‘Advocare—our call to act’, ‘The paradox of primary care and three simple rules’, ‘The quadruple aim—melding the patient and the health system’, ‘Fit-for-purpose medical workforce’, ‘Universal healthcare—coverage for all’, ‘The futures of family …


Liver-Directed Locoregional Therapies For Neuroendocrine Liver Metastases: Recent Advances And Management., Cody R Criss, Mina S Makary Apr 2024

Liver-Directed Locoregional Therapies For Neuroendocrine Liver Metastases: Recent Advances And Management., Cody R Criss, Mina S Makary

Oncology Articles

Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients' quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of …


Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc Apr 2024

Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc

Faculty, Staff and Student Publications

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin.

METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) …


Neonatal Outcomes In The Surgical Management Of Placenta Accreta Spectrum Disorders: A Retrospective Single-Center Observational Study From 468 Vietnamese Pregnancies Beyond 28 Weeks Of Gestation, Phuc Nhon Nguyen, Anh Dinh Bao Vuong, Xuan Trang Thi Pham Apr 2024

Neonatal Outcomes In The Surgical Management Of Placenta Accreta Spectrum Disorders: A Retrospective Single-Center Observational Study From 468 Vietnamese Pregnancies Beyond 28 Weeks Of Gestation, Phuc Nhon Nguyen, Anh Dinh Bao Vuong, Xuan Trang Thi Pham

Faculty, Staff and Student Publications

BACKGROUND: Placenta accreta spectrum disorders (PASDs) increase the mortality rate for mothers and newborns over a decade. Thus, the purpose of the study is to evaluate the neonatal outcomes in emergency cesarean section (CS) and planned surgery as well as in Cesarean hysterectomy and the modified one-step conservative uterine surgery (MOSCUS). The secondary aim is to reveal the factors relating to poor neonatal outcomes.

METHODS: This was a single-center retrospective study conducted between 2019 and 2020 at Tu Du Hospital, in the southern region of Vietnam. A total of 497 pregnant women involved in PASDs beyond 28 weeks of gestation …


The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens Apr 2024

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …


Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis Apr 2024

Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19.

METHODS: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention …


Risk Factors For In-Hospital Seizure And New-Onset Epilepsy In Coiling And Clipping Treatment Of Aneurysmal Subarachnoid Hemorrhage, Viet-Thang Le, Anh Minh Nguyen, Phuc Long Nguyen Apr 2024

Risk Factors For In-Hospital Seizure And New-Onset Epilepsy In Coiling And Clipping Treatment Of Aneurysmal Subarachnoid Hemorrhage, Viet-Thang Le, Anh Minh Nguyen, Phuc Long Nguyen

Faculty, Staff and Student Publications

OBJECTIVE: To identify risk factors associated with in-hospital seizures and new-onset epilepsy in patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent coiling embolization or clipping surgery.

METHODS: This retrospective descriptive study included 195 patients diagnosed with aneurysmal SAH and treated with coiling embolization or clipping surgery between January 2018 and June 2022.

RESULTS: Among the 195 patients meeting inclusion criteria, 9 experienced an onset seizure at the time of SAH. In-hospital seizures were observed in 33 patients, of which 24 were electrographic seizures detected in 24 patients with suspected subclinical seizures. After 12 months of follow-up, 11 patients met criteria …


Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik Apr 2024

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …


Machine Learning-Enabled Maternal Risk Assessment For Women With Pre-Eclampsia (The Piers-Ml Model): A Modelling Study, Tünde Montgomery-Csobán, Kimberley Kavanagh, Paul Murray, Chris Robertson, Sarah J E Barry, U Vivian Ukah, Beth A Payne, Kypros H Nicolaides, Argyro Syngelaki, Olivia Ionescu, Ranjit Akolekar, Jennifer A Hutcheon, Laura A Magee, Peter Von Dadelszen, Piers Consortium Apr 2024

Machine Learning-Enabled Maternal Risk Assessment For Women With Pre-Eclampsia (The Piers-Ml Model): A Modelling Study, Tünde Montgomery-Csobán, Kimberley Kavanagh, Paul Murray, Chris Robertson, Sarah J E Barry, U Vivian Ukah, Beth A Payne, Kypros H Nicolaides, Argyro Syngelaki, Olivia Ionescu, Ranjit Akolekar, Jennifer A Hutcheon, Laura A Magee, Peter Von Dadelszen, Piers Consortium

Faculty, Staff and Student Publications

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia.

METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of …


Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez Apr 2024

Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution …


Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi Mar 2024

Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).

METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at …


Case 9-2024: An 84-Year-Old Man With A Fall, Zaven Sargsyan, Sunita D Srivastava, Virginia A Triant, Brian B Ghoshhajra Mar 2024

Case 9-2024: An 84-Year-Old Man With A Fall, Zaven Sargsyan, Sunita D Srivastava, Virginia A Triant, Brian B Ghoshhajra

Faculty, Staff and Students Publications

No abstract provided.


Single-Cell Analysis Of Age-Related Changes In Leukocytes Of Diabetic Mouse Hindpaws, James M Nichols, Hoang Vu Pham, Eric F Lee, Rajasekaran Mahalingam, Andrew J Shepherd Mar 2024

Single-Cell Analysis Of Age-Related Changes In Leukocytes Of Diabetic Mouse Hindpaws, James M Nichols, Hoang Vu Pham, Eric F Lee, Rajasekaran Mahalingam, Andrew J Shepherd

Faculty, Staff and Student Publications

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the …


Germline Structural Variation Globally Impacts The Cancer Transcriptome Including Disease-Relevant Genes, Fengju Chen, Yiqun Zhang, Fritz J Sedlazeck, Chad J Creighton Mar 2024

Germline Structural Variation Globally Impacts The Cancer Transcriptome Including Disease-Relevant Genes, Fengju Chen, Yiqun Zhang, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Germline variation and somatic alterations contribute to the molecular profile of cancers. We combine RNA with whole genome sequencing across 1,218 cancer patients to determine the extent germline structural variants (SVs) impact expression of nearby genes. For hundreds of genes, recurrent and common germline SV breakpoints within 100 kb associate with increased or decreased expression in tumors spanning various tissues of origin. A significant fraction of germline SV expression associations involves duplication of intergenic enhancers or 3' UTR disruption. Genes altered by both somatic and germline SVs include ATRX and CEBPA. Genes essential in cancer cell lines include BARD1 and …


Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla Mar 2024

Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' …


Cd69 Signaling In Eosinophils Induces Il-10 Production And Apoptosis Via The Erk1/2 And Jnk Pathways, Respectively, Dan Van Bui, Linh Manh Nguyen, Akira Kanda, Hanh Hong Chu, Nhi Kieu Thi Le, Yasutaka Yun, Yoshiki Kobayashi, Kensuke Suzuki, Akitoshi Mitani, Akihiro Shimamura, Kenta Fukui, Shunsuke Sawada, David Dombrowicz, Hiroshi Iwai Mar 2024

Cd69 Signaling In Eosinophils Induces Il-10 Production And Apoptosis Via The Erk1/2 And Jnk Pathways, Respectively, Dan Van Bui, Linh Manh Nguyen, Akira Kanda, Hanh Hong Chu, Nhi Kieu Thi Le, Yasutaka Yun, Yoshiki Kobayashi, Kensuke Suzuki, Akitoshi Mitani, Akihiro Shimamura, Kenta Fukui, Shunsuke Sawada, David Dombrowicz, Hiroshi Iwai

Faculty, Staff and Student Publications

INTRODUCTION: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear.

METHODS: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked …


Cns-Associated Macrophages Contribute To Intracerebral Aneurysm Pathophysiology, Martina Glavan, Ana Jelic, Damien Levard, Juhana Frösen, Sara Keränen, Bart A A Franx, Ana-Rita Bras, Estelle R Louet, Ádám Dénes, Mario Merlini, Denis Vivien, Marina Rubio Mar 2024

Cns-Associated Macrophages Contribute To Intracerebral Aneurysm Pathophysiology, Martina Glavan, Ana Jelic, Damien Levard, Juhana Frösen, Sara Keränen, Bart A A Franx, Ana-Rita Bras, Estelle R Louet, Ádám Dénes, Mario Merlini, Denis Vivien, Marina Rubio

Faculty, Staff and Student Publications

Simple Summary

Vestibular schwannoma (VS), benign cranial nerve sheath tumors of the vestibulocochlear nerve, lack efficacious systemic therapies, especially if they develop in a NF2-related schwannomatosis (NF2) background. They cause hearing loss, tinnitus and balance problems. Metastasis associated in colon cancer 1 (MACC1) is a key driver of metastasis. Although MACC1 expression is associated with highly malignant tumors and VS are considered benign, both are attached to the HGF/MET signaling pathway and MACC1 is a candidate gene localized at a hearing loss-related gene locus. Therefore, it was investigated whether MACC1 might be involved in VS pathogenesis. Surprisingly, MACC1 expression …


Using Protein Language Models For Protein Interaction Hot Spot Prediction With Limited Data, Karen Sargsyan, Carmay Lim Mar 2024

Using Protein Language Models For Protein Interaction Hot Spot Prediction With Limited Data, Karen Sargsyan, Carmay Lim

Faculty, Staff and Student Publications

BACKGROUND: Protein language models, inspired by the success of large language models in deciphering human language, have emerged as powerful tools for unraveling the intricate code of life inscribed within protein sequences. They have gained significant attention for their promising applications across various areas, including the sequence-based prediction of secondary and tertiary protein structure, the discovery of new functional protein sequences/folds, and the assessment of mutational impact on protein fitness. However, their utility in learning to predict protein residue properties based on scant datasets, such as protein-protein interaction (PPI)-hotspots whose mutations significantly impair PPIs, remained unclear. Here, we explore the …


The Effect Of Severe Intraventricular Hemorrhage On The Biorhythms Of Feeding In Premature Infants, Hyun Ho Choi, Soo-Yoon Sung, Bo-In Lee, Hyun Cho, Yunho Jung, Jae Myung Park, Young-Seok Cho, Kang-Moon Lee, Sang Woo Kim, Hwang Choi, Hiun-Suk Chae, Myung-Gyu Choi Mar 2024

The Effect Of Severe Intraventricular Hemorrhage On The Biorhythms Of Feeding In Premature Infants, Hyun Ho Choi, Soo-Yoon Sung, Bo-In Lee, Hyun Cho, Yunho Jung, Jae Myung Park, Young-Seok Cho, Kang-Moon Lee, Sang Woo Kim, Hwang Choi, Hiun-Suk Chae, Myung-Gyu Choi

Faculty, Staff and Student Publications

BACKGROUND/AIMS: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality.

METHODS: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted "quality education" session. The personality traits of each …


Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko Mar 2024

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …


Utility Of Peripheral Protein Biomarkers For The Prediction Of Incident Interstitial Features: A Multicentre Retrospective Cohort Study, Samuel Ash, Tracy J Doyle, Bina Choi, Ruben San Jose Estepar, Victor Castro, Nicholas Enzer, Ravi Kalhan, Gabrielle Liu, Russell Bowler, David O Wilson, Raul San Jose Estepar, Ivan O Rosas, George R Washko Mar 2024

Utility Of Peripheral Protein Biomarkers For The Prediction Of Incident Interstitial Features: A Multicentre Retrospective Cohort Study, Samuel Ash, Tracy J Doyle, Bina Choi, Ruben San Jose Estepar, Victor Castro, Nicholas Enzer, Ravi Kalhan, Gabrielle Liu, Russell Bowler, David O Wilson, Raul San Jose Estepar, Ivan O Rosas, George R Washko

Faculty, Staff and Students Publications

INTRODUCTION/RATIONALE: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT.

METHODS: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without objectively measured interstitial features at baseline using a univariate screen (t-test false discovery rate, FDR p

RESULTS: In COPDGene, 1305 biomarkers were available and 20 differed between those with and without interstitial features at baseline. Of these, 11 were associated with feature progression over a mean of 5.5 years of follow-up, and of these 4 were available in PLuSS, (angiopoietin-2, matrix metalloproteinase 7, macrophage inflammatory protein 1 …


Methodological Advances In Patient-Centered Rare Disease Research: The Uthealth Houston Turner Syndrome Society Of The United States Research Registry, Sara Mansoorshahi, Cindy Scurlock, Scientific Advisory Board Of The Turner Syndrome Society Of The United States Research Registry, Siddharth K Prakash Mar 2024

Methodological Advances In Patient-Centered Rare Disease Research: The Uthealth Houston Turner Syndrome Society Of The United States Research Registry, Sara Mansoorshahi, Cindy Scurlock, Scientific Advisory Board Of The Turner Syndrome Society Of The United States Research Registry, Siddharth K Prakash

Faculty, Staff and Student Publications

BACKGROUND: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers.

RESULTS: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston …


Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton Mar 2024

Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton

Faculty, Staff and Student Publications

IMPORTANCE: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed.

OBJECTIVE: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the …