Public Health Commons^™

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 …

The Value Of Global Collaborations, Chris Trauernicht, Laurence Court

Faculty, Staff and Student Publications

No abstract provided.

Critical Role Of Histone Deacetylase 3 In The Regulation Of Kidney Inflammation And Fibrosis, Yuguo Wang, Baihai Jiao, Zhaoyong Hu, Yanlin Wang

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is characterized by kidney inflammation and fibrosis. However, the precise mechanisms leading to kidney inflammation and fibrosis are poorly understood. Since histone deacetylase is involved in inflammation and fibrosis in other tissues, we examined the role of histone deacetylase 3 (HDAC3) in the regulation of inflammation and kidney fibrosis. HDAC3 is induced in the kidneys of animal models of CKD but mice with conditional HDAC3 deletion exhibit significantly reduced fibrosis in the kidneys compared with control mice. The expression of proinflammatory and profibrotic genes was significantly increased in the fibrotic kidneys of control mice, which was …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Alveolar Epithelial Cell Dysfunction In Idiopathic Pulmonary Fibrosis Linked To Lipid Alterations: Therapeutic Implications, Francesca Polverino, Ana Mora

Faculty, Staff and Students Publications

No abstract provided.

A Mutation In Tbxt Causes Congenital Vertebral Malformations In Humans And Mice, Shuxia Chen, Yunping Lei, Yajun Yang, Chennan Liu, Lele Kuang, Li Jin, Richard H Finnell, Xueyan Yang, Hongyan Wang

Faculty, Staff and Students Publications

T-box transcription factor T (TBXT; T) is required for mesodermal formation and axial skeletal development. Although it has been extensively studied in various model organisms, human congenital vertebral malformations (CVMs) involving T are not well established. Here, we report a family with 15 CVM patients distributed across 4 generations. All affected individuals carry a heterozygous mutation, T c.596A>G (p.Q199R), which is not found in unaffected family members, indicating co-segregation of the genotype and phenotype. In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity, but reduces its transcriptional activity compared to the wild-type. …

Virtual Multi-Institutional Tumor Board: A Strategy For Personalized Diagnoses And Management Of Rare Cns Tumors, James L Rogers, Thomas Wall, Alvina A Acquaye-Mallory, Lisa Boris, Yeonju Kim, Kenneth Aldape, Martha M Quezado, John A Butman, James G Smirniotopoulos, Huma Chaudhry, Christina I Tsien, Prashant Chittiboina, Kareem Zaghloul, Orwa Aboud, Nicholas G Avgeropoulos, Eric C Burton, David M Cachia, Karan S Dixit, Jan Drappatz, Erin M Dunbar, Peter Forsyth, Edina Komlodi-Pasztor, Jacob Mandel, Byram H Ozer, Eudocia Q Lee, Surabhi Ranjan, Rimas V Lukas, Margarita Raygada, Michael E Salacz, Matthew A Smith-Cohn, James Snyder, Ariane Soldatos, Brett J Theeler, Brigitte C Widemann, Kevin A Camphausen, John D Heiss, Terri S Armstrong, Mark R Gilbert, Marta Penas-Prado

Faculty, Staff and Students Publications

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers.

METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management …

Re-Evaluation Of The Methodology For Estimating The Us Specialty Physician Workforce, W Stephen Black-Schaffer, David J Gross, Zakia Nouri, Aidan Delisle, Michael Dill, Jason Y Park, James M Crawford, Michael B Cohen, Rebecca L Johnson, Donald S Karcher, Thomas M Wheeler, Stanley J Robboy

Faculty, Staff and Students Publications

Increasing pursuit of subspecialized training has quietly revolutionized physician training, but the potential impact on physician workforce estimates has not previously been recognized. The Physicians Specialty Data Reports of the Association of American Medical Colleges, derived from specialty designations in the American Medical Association (AMA) Physician Professional Data (PPD), are the reference source for US physician workforce estimates; by 2020, the report for pathologists was an undercount of 39% when compared with the PPD. Most of the difference was due to the omission of pathology subspecialty designations. The rest resulted from reliance on only the first of the AMA PPD's …

Load703, An Oncolytic Virus-Based Immunostimulatory Gene Therapy, Combined With Chemotherapy For Unresectable Or Metastatic Pancreatic Cancer (Lokon001): Results From Arm 1 Of A Non-Randomised, Single-Centre, Phase 1/2 Study, Benjamin L Musher, Eric K Rowinsky, Brandon G Smaglo, Wasif Abidi, Mohamed Othman, Kalpesh Patel, Salmaan Jawaid, James Jing, Amanda Brisco, Ann M Leen, Mengfen Wu, Linda C Sandin, Jessica Wenthe, Emma Eriksson, Gustav J Ullenhag, Bambi Grilley, Justyna Leja-Jarblad, Susan G Hilsenbeck, Malcolm K Brenner, Angelica S I Loskog

Faculty, Staff and Students Publications

Background: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma.

Methods: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. …

Pre-Covid-19 Hospital Quality And Hospital Response To Covid-19: Examining Associations Between Risk-Adjusted Mortality For Patients Hospitalised With Covid-19 And Pre-Covid-19 Hospital Quality, Doris Peter, Shu-Xia Li, Yongfei Wang, Jing Zhang, Jacqueline Grady, Kerry Mcdowell, Erica Norton, Zhenqiu Lin, Susannah Bernheim, Arjun K Venkatesh, Lee A Fleisher, Michelle Schreiber, Lisa G Suter, Elizabeth W Triche

Faculty, Staff and Student Publications

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19.

DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics.

SETTING: Short-term acute care hospitals and critical access hospitals in the USA.

PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised …

Ndrgs In Breast Cancer: A Review And In Silico Analysis, Emilly S Villodre, Anh P N Nguyen, Bisrat G Debeb

Faculty, Staff and Student Publications

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissuejove: Peer Reviewed Scientific Video Journal Article Protocols, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Faculty, Staff and Students Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Study Protocol: Identifying Transcriptional Regulatory Alterations Of Chronic Effects Of Blast And Disturbed Sleep In United States Veterans, Molly J. Sullan, Kelly A. Stearns-Yoder, Zhaoyu Wang, Andrew J. Hoisington, Adam D. Brenoweth, Walter Carr, Yongchao Ge, Hanga Galfalvy, Fatemah Haghighi, Lisa A. Brenner

Faculty Publications

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of …

Sex-Based Differences In Melanoma Survival Improvement From 2004 To 2018, Vikram R Shaw, Angela Hudock, Baoyi Zhang, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

Simple Summary

Melanoma is the deadliest form of skin cancer and its incidence and mortality may vary by demographic factors, such as sex, age, race, and socioeconomic status. Few studies, however, have characterized disparities in survival improvement across these demographic groups in melanoma. In the present study, the authors highlight disparities in melanoma survival improvement, both in diagnosed melanoma and carcinoma in situ. While melanoma survival has improved overall, some patient subgroups have experienced a lower improvement in survival from 2004 to 2018.

Abstract

Background: Melanoma is the deadliest form of skin cancer and its incidence and mortality vary by …

Definitions And Measurements For Atypical Presentations At Risk For Diagnostic Errors In Internal Medicine: Protocol For A Scoping Review, Yukinori Harada, Ren Kawamura, Masashi Yokose, Taro Shimizu, Hardeep Singh

Faculty, Staff and Students Publications

BACKGROUND: Atypical presentations have been increasingly recognized as a significant contributing factor to diagnostic errors in internal medicine. However, research to address associations between atypical presentations and diagnostic errors has not been evaluated due to the lack of widely applicable definitions and criteria for what is considered an atypical presentation.

OBJECTIVE: The aim of the study is to describe how atypical presentations are defined and measured in studies of diagnostic errors in internal medicine and use this new information to develop new criteria to identify atypical presentations at high risk for diagnostic errors.

METHODS: This study will follow an established …

The Ethics And Practice Of Periviability Care, Alex C Vidaeff, Joseph W Kaempf

Faculty, Staff and Students Publications

Since the 1960s, the gestational age at which premature infants typically survive has decreased by approximately one week per decade [1]. Survival is now reported at remarkably early gestational ages. In 2022, the Vermont Oxford Network reported neonatal intensive care unit (NICU) survival rates of 21%, 46%, and 63% at 22, 23, and 24 weeks’ gestation [2]. Presently, in industrialized nations, the so-called periviability interval refers to the gestational age period of possible survival that extends from approximately 22 to 25 weeks’ gestation. Newborns born within this period are distinguished by their need for extraordinarily complex …

Development Of Solitary Keratoacanthoma From A Cutaneous Wart, Joshua M. Ninan, Veronica Salazar

Research Symposium

Background: Common cutaneous warts, referred to in medicine as verrucae vulgaris, are proliferative lesions caused by human papillomavirus. These lesions are mostly benign and usually resolve without incident, except in the case of the patient mentioned in this report. Our patient developed a solitary keratoacanthoma, currently accepted as a clinical variant of squamous cell carcinoma, as a result of several risk factors and traumatic exposure. The current literature does not have an established association of HPV with solitary keratoacanthomas. This case report explores the presentation and pathogenesis of solitary keratoacanthomas within the setting of HPV.

Case Presentation: 48-year-old Caucasian female …

Tissue-Resident Memory T Cell Signatures From Single-Cell Analysis Associated With Better Melanoma Prognosis, Chongming Jiang, Cheng-Chi Chao, Jianrong Li, Xin Ge, Aidan Shen, Vadim Jucaud, Chao Cheng, Xiling Shen

Faculty, Staff and Students Publications

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM–derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall …

A Journey In Science: Molecular Vaccines For Global Child Health In Troubled Times Of Anti-Science, Peter J Hotez

Faculty, Staff and Students Publications

My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for parasitic and neglected tropical diseases, as well as pandemic threats. This includes a vaccine for human hookworm infection that I began as an MD-PhD student in New York City in the 1980s, and a new low-cost COVID vaccine that reached almost 100 million people in low- and middle-income countries. Alongside this life in scientific research, is one in public engagement for vaccine and neglected disease diplomacy to ensure that people who live in extreme poverty can …

Dolutegravir-Induced Neural Tube Defects In Mice Are Folate Responsive, Gabriel L Tukeman, Hui Wei, Ying L Lin, Bogdan J Wlodarczyk, Richard H Finnell, Robert M Cabrera

Faculty, Staff and Students Publications

Objectives: In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy.

Design: DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet.

Methods: CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. …

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, Activ-3/Tico Study Group

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 …

Biomechanical Analysis Of The Maxillary Sinus Floor Membrane During Internal Sinus Floor Elevation With Implants At Different Angles Of The Maxillary Sinus Angles, Yinxin Deng, Ruihong Ma, Yilin He, Shujia Yu, Shiyu Cao, Kang Gao, Yiping Dou, Pan Ma

Faculty, Staff and Student Publications

OBJECTIVE: This study analyzed and compared the biomechanical properties of maxillary sinus floor mucosa with implants at three different maxillary sinus angles during a modified internal sinus floor elevation procedure.

METHODS: 3D reconstruction of the implant, maxillary sinus bone, and membrane were performed. The maxillary sinus model was set at three different angles. Two internal maxillary sinus elevation models were established, and finite element analysis was used to simulate the modified maxillary sinus elevation process. The implant was elevated to 10 mm at three maxillary sinus angles when the maxillary sinus floor membrane was separated by 0 and 4 mm. …

Landscape Of Pharmacogenetic Variants Associated With Non-Insulin Antidiabetic Drugs In The Indian Population, Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Arpita Mukhopadhyay, Greg Gibson, Km Venkat Narayan, Sridhar Sivasubbu, Vinod Scaria, Anura V Kurpad

Faculty, Staff and Student Publications

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with …

Learning From The Implementation Of A Surgical Opioid Reduction Initiative In An Integrated Health System: A Qualitative Study Among Providers And Patients, Willemijn L A Schäfer, Julie K Johnson, Meagan S Ager, Cassandra B Iroz, Reiping Huang, Salva N Balbale, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Surgical opioid overprescribing can result in long-term use or misuse. Between July 2018 and March 2019, the multicomponent intervention, Minimizing Opioid Prescribing in Surgery (MOPiS) was implemented in the general surgery clinics of five hospitals and successfully reduced opioid prescribing. To date, various studies have shown a positive outcome of similar reduction initiatives. However, in addition to evaluating the impact on clinical outcomes, it is important to understand the implementation process of an intervention to extend sustainability of interventions and allow for dissemination of the intervention into other contexts. This study aims to evaluate the contextual factors impacting intervention …

Racial And Socioeconomic Disparities In Survival Improvement Of Eight Cancers, Vikram Shaw, Baoyi Zhang, Mabel Tang, William Peng, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

BACKGROUND: Many studies have characterized racial differences in cancer outcomes, demonstrating that black and Hispanic patients have lower cancer-specific survival compared to white patients. However, to our knowledge, a gap in the literature exists regarding racial, socioeconomic, age, and sex-related differences in survival improvement in cancer.

METHODS: We perform a population-based cohort study of 1,875,281 patients with eight common cancer sites from the Surveillance, Epidemiology, and End Results (SEER) database.

RESULTS: The longitudinal data demonstrates that while overall cancer-free survival has improved from 2004 to 2018, certain groups have seen lower rates of improvement. Black patients have the lowest cancer-specific …

Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari

School of Medicine Faculty Publications

No abstract provided.

Immuno-Molecular Targeted Therapy Use And Survival Benefit In Patients With Stage Ivb Cervical Carcinoma In Commission On Cancer, Collin A Sitler, Chunqiao Tian, Chad A Hamilton, Michael T Richardson, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christina Washington, Nicole P Chappell, Ann H Klopp, Craig D Shriver, Christopher M Tarney, Nicholas W Bateman, Thomas P Conrads, George Larry Maxwell, Neil T Phippen, Kathleen M Darcy

Faculty, Staff and Student Publications

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials.

METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates.

RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use …

Enhancing Prognostic Power In Multiple Myeloma Using A Plasma Cell Signature Derived From Single-Cell Rna Sequencing, Jian-Rong Li, Shahram Arsang-Jang, Yan Cheng, Fumou Sun, Anita D'Souza, Binod Dhakal, Parameswaran Hari, Quillan Huang, Paul Auer, Yong Li, Raul Urrutia, Fenghuang Zhan, John D Shaughnessy, Siegfried Janz, Jing Dong, Chao Cheng

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum …

Prenatal, Perinatal And Postnatal Risk Factors Associated With Autism Spectrum Disorder In Palestine: A Case-Control Study, Mustafa Ghanim, Mariam Al-Tell, Samaa Staiti, Maha Rabayaa, Johnny Amer, Malik Alqub, Sameeha Atout, Nihad Al-Othman, Marwa Ismail

An-Najah University Journal for Research - B (Humanities)

Background: Autism spectrum disorder (ASD) is a multifactorial neurodevelopment disorder. Several prenatal, perinatal, and postnatal factors are suggested as risk factors for ASD. This study aimed to correlate prenatal, perinatal, and postnatal factors in a limited number of ASD cases in Palestine. Methods: A case-control study involved 120 children (60 typically diagnosed with ASD and 60 healthy matched with the ASD group). The parents of the children in both groups were asked to fill out the questionnaire. Results: The study showed a higher male-to-female ratio in the ASD group. A family history of ASD was reported in 38.3% of the …

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Pooja Popli, Zian Liao, Eryk Andreas, Michelle Dias, Tianyuan Wang, Stephanie J Gunderson, Patricia T Jimenez, Denise G Lanza, Rainer B Lanz, Charles E Foulds, Diana Monsivais, Francesco J Demayo, Hari Krishna Yalamanchili, Emily S Jungheim, Jason D Heaney, John P Lydon, Kelle H Moley, Bert W O'Malley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …