Medicine and Health Sciences Commons^™

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 …

What Do Cervical Cancer Patients Know, How Do They Learn, And Who Do They Tell? A Pilot Study, Sharon Larson, Brian Mcanany, Ilene Ladd, Radhika Gogoi

College of Population Health Faculty Papers

BACKGROUND: This study explored what patients identified with cervical cancer know about the link between human papillomavirus (HPV) and cervical cancer and where they learned this information. Patients share a great deal of information with family, friends and colleagues and we were interested in the accuracy and sources of information they are sharing.

METHODS: Patients identified through the EHR of a health system who had a history of cervical cancer were invited to participate in a brief survey of their experience. The sample represents an opportunity sample of patients who responded.

RESULTS: Generally, these patients, drawn from the Geisinger Health …

Fungi Of The Order Mucorales Express A “Sealing-Only” Trna Ligase, Khondakar Sayef Ahammed, Ambro Van Hoof

Faculty, Staff and Student Publications

Some eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease, followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promising drug target for fungal infections. To validate Trl1 as a broad-spectrum drug target, we show that …

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' …

Prophylactic Defunctioning Stomas Improve Clinical Outcomes Of Anastomotic Leak Following Rectal Cancer Resections: An Analysis Of The Us Rectal Cancer Consortium, Katherine Hrebinko, Vincent P Anto, Katherine M Reitz, Adriana C Gamboa, Scott E Regenbogen, Alexander T Hawkins, M Benjamin Hopkins, Aslam Ejaz, Philip S Bauer, Paul E Wise, Glen C Balch, Jennifer Holder-Murray

2020-Current year OA Pubs

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes.

METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did …

Htra1 Disaggregates Α-Synuclein Amyloid Fibrils And Converts Them Into Non-Toxic And Seeding Incompetent Species, Sheng Chen, Anuradhika Puri, Braxton Bell, Joseph Fritsche, Hector H Palacios, Maurie Balch, Macy L Sprunger, Matthew K Howard, Jeremy J Ryan, Jessica N Haines, Gary J Patti, Albert A Davis, Meredith E Jackrel

2020-Current year OA Pubs

Parkinson's disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with Alzheimer's disease, and inactivating mutations to mitochondrial HTRA2 are implicated in PD. Here, we report that HTRA1 inhibits aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The protease domain of HTRA1 is necessary and sufficient for inhibiting aggregation, yet this activity is proteolytically-independent. Further, HTRA1 disaggregates preformed α-syn fibrils, rendering them incapable of seeding aggregation of endogenous α-syn, while reducing HTRA1 …

A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. …

Automated Seizure Detection Based On State-Space Model Identification, Zhuo Wang, Michael Sperling, Dale Wyeth, Allon Guez

Department of Neuroscience Faculty Papers

In this study, we developed a machine learning model for automated seizure detection using system identification techniques on EEG recordings. System identification builds mathematical models from a time series signal and uses a small number of parameters to represent the entirety of time domain signal epochs. Such parameters were used as features for the classifiers in our study. We analyzed 69 seizure and 55 non-seizure recordings and an additional 10 continuous recordings from Thomas Jefferson University Hospital, alongside a larger dataset from the CHB-MIT database. By dividing EEGs into epochs (1 s, 2 s, 5 s, and 10 s) and …

Treatment Setting And Buprenorphine Discontinuation: An Analysis Of Multi-State Insurance Claims, Kevin Y Xu, Alex K Gertner, Shelly F Greenfield, Arthur Robin Williams, Richard A Grucza

2020-Current year OA Pubs

BACKGROUND: Potential differences in buprenorphine treatment outcomes across various treatment settings are poorly characterized in multi-state administrative data. We thus evaluated the association of opioid use disorder (OUD) treatment setting and insurance type with risk of buprenorphine discontinuation among commercial insurance and Medicaid enrollees initiated on buprenorphine.

METHODS: In this observational, retrospective cohort study using the Merative MarketScan databases (2006-2016), we analyzed buprenorphine retention in 58,200 US adults with OUD. Predictor variables included insurance status (Medicaid vs commercial) and treatment setting, operationalized as substance use disorder (SUD) specialty treatment facility versus outpatient primary care physicians (PCPs) versus outpatient psychiatry, ascertained …

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 Novel Drug Candidate S2/Iapinh Improves Survival In Models Of Pancreatic And Ovarian Cancer, Takaomi Hagi, Suwanna Vangveravong, Rony Takchi, Qingqing Gong, S Peter Goedegebuure, Herve Tiriac, Brian A Van Tine, Matthew A Powell, William G Hawkins, Dirk Spitzer

2020-Current year OA Pubs

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in …

Long Noncoding Rna Malat1 Protects Against Osteoporosis And Bone Metastasis, Yang Zhao, Jingyuan Ning, Hongqi Teng, Yalan Deng, Marisela Sheldon, Lei Shi, Consuelo Martinez, Jie Zhang, Annie Tian, Yutong Sun, Shinichi Nakagawa, Fan Yao, Hai Wang, Li Ma

Faculty, Staff and Student Publications

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, …

Deep Sequencing Of Candidate Genes Identified 14 Variants Associated With Smoking Abstinence In An Ethnically Diverse Sample, Paul M Cinciripini, David W Wetter, Jian Wang, Robert Yu, George Kypriotakis, Tapsi Kumar, Jason D Robinson, Yong Cui, Charles E Green, Andrew W Bergen, Thomas R Kosten, Steven E Scherer, Sanjay Shete

Faculty, Staff and Student Publications

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 …

Exploration Of Latina/Hispanic Women's Experiences Living With Non-Alcoholic Fatty Liver Disease: A Qualitative Study With Patients In Houston, Natalia I Heredia, Erika Mendoza Duque, Sylvia Ayieko, Amelia Averyt, Lorna H Mcneill, Jessica P Hwang, Maria E Fernandez

Faculty, Staff and Student Publications

OBJECTIVES: A deeper understanding of the lived experiences of Hispanic patients with non-alcoholic fatty liver disease (NAFLD) can help guide the development of behavioral programs that facilitate NAFLD management. This paper explores Hispanic women's experiences living with NAFLD.

DESIGN, SETTING, PARTICIPANTS: We collected brief sociodemographic questionnaires and conducted in-depth interviews with 12 low-income (all had household income ≤USD$55 000 per year) Hispanic women with NAFLD from the Houston area. Transcripts were audio-recorded and transcribed. We developed a coding scheme and used thematic analysis to identify emergent themes, supported by Atlas.ti.

RESULTS: Participants identified physicians as their main information source on …

Defining Clinical Endpoints In Limb Girdle Muscular Dystrophy: A Grasp-Lgmd Study, Amy Doody, Lindsay Alfano, Jordi Diaz-Manera, Linda Lowes, Tahseen Mozaffar, Katherine D Mathews, Conrad C Weihl, Matthew Wicklund, Man Hung, Jeffrey Statland, Nicholas E Johnson, Grasp-Lgmd Consortium

2020-Current year OA Pubs

BACKGROUND: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders.

METHODS/DESIGN: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established …

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 …

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. …

Sabr For Sarcoma Lung Metastases: Indications For Treatment And Guidance For Patient Selection, Ahsan S Farooqi, Alison K Yoder, Heather Y Lin, Dario Pasalic, Jeremy Erasmus, Sonia Betancourt, Cort Wernz, Devarati Mitra, Maria A Zarzour, Neeta Somaiah, Anthony Conley, Ravin Ratan, Andrew Livingston, Dejka M Araujo, Christina Roland, Christopher Scally, Emily Keung, Saumil N Gandhi, B Ashleigh Guadagnolo, Quynh-Nhu Nguyen, Andrew J Bishop

Faculty, Staff and Student Publications

Purpose: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases.

Methods and materials: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable …

Clonal Dominance Defines Metastatic Dissemination In Pancreatic Cancer, I-Lin Ho, Chieh-Yuan Li, Fuchenchu Wang, Li Zhao, Jingjing Liu, Er-Yen Yen, Charles A Dyke, Rutvi Shah, Zhaoliang Liu, Ali Osman Çetin, Yanshuo Chu, Francesca Citron, Sergio Attanasio, Denise Corti, Faezeh Darbaniyan, Edoardo Del Poggetto, Sara Loponte, Jintan Liu, Melinda Soeung, Ziheng Chen, Shan Jiang, Hong Jiang, Akira Inoue, Sisi Gao, Angela Deem, Ningping Feng, Haoqiang Ying, Michael Kim, Virginia Giuliani, Giannicola Genovese, Jianhua Zhang, Andrew Futreal, Anirban Maitra, Timothy Heffernan, Linghua Wang, Kim-Anh Do, Gaetano Gargiulo, Giulio Draetta, Alessandro Carugo, Ruitao Lin, Andrea Viale

Faculty, Staff and Student Publications

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth …

Toward Clinical-Grade Evaluation Of Large Language Models, Amy C Moreno, Danielle S Bitterman

Faculty, Staff and Student Publications

No abstract provided.

Phase I Study Of Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Enzalutamide In Patients With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide, Wassim Abida, Andrew W Hahn, Neal Shore, Neeraj Agarwal, Paul Sieber, Matthew R Smith, Tanya Dorff, Paul Monk, Matthew Rettig, Rupal Patel, Anne Page, Maureen Duff, Rongda Xu, Jian Wang, Shravani Barkund, Aleksandr Pankov, Amber Wang, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Christopher J Logothetis, Michael J Morris

Faculty, Staff and Student Publications

Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.

Patients and methods: Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase …

Validation Of A Multiomic Model Of Plasma Extracellular Vesicle Pd-L1 And Radiomics For Prediction Of Response To Immunotherapy In Nsclc, Diego De Miguel-Perez, Murat Ak, Priyadarshini Mamindla, Alessandro Russo, Serafettin Zenkin, Nursima Ak, Vishal Peddagangireddy, Luis Lara-Mejia, Muthukumar Gunasekaran, Andres F Cardona, Aung Naing, Fred R Hirsch, Oscar Arrieta, Rivka R Colen, Christian Rolfo

Faculty, Staff and Student Publications

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs.

MAIN BODY: Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed …

Case Report: Molecular Profiling Facilitates The Diagnosis Of A Challenging Case Of Lung Cancer With Choriocarcinoma Features, Hui Li, Xin Hu, Matthew S Ning, Gregory N Fuller, John M Stewart, Jared C Gilliam, Jia Wu, Xiuning Le, Ara A Vaporciyan, J Jack Lee, Don L Gibbons, John V Heymach, Andrew Futreal, Jianjun Zhang

Faculty, Staff and Student Publications

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of …

The Digital Transition: Are Adults Aged 65 Years Or Older Willing To Complete Online Forms And Questionnaires In Patient Portals?, Nancy P Gordon, Sherry Zhang, Joan C Lo, Christina F Li

Faculty, Staff and Student Publications

INTRODUCTION: Patients are being encouraged to complete forms electronically using patient portals rather than on paper, but willingness of older adults to make this transition is uncertain.

METHODS: The authors analyzed data for 4105 Kaiser Permanente Northern California 2020 Member Health Survey respondents aged 65-85 years who answered a question about willingness to complete online forms and questionnaires using a patient portal. Data weighted to the Kaiser Permanente Northern California membership were used to estimate percentages of older adults willing to complete patient portal forms and questionnaires. Chi-square tests and log-Poisson regression models that included sociodemographic, internet use, and patient …

Safety And Efficacy Of Ibrutinib In Combination With Rituximab And Lenalidomide In Previously Untreated Follicular And Marginal Zone Lymphoma: An Open Label, Phase 2 Study, Max J Gordon, Lei Feng, Paolo Strati, Hun Ju Lee, Fredrick B Hagemeister, Jason R Westin, Felipe Samaniego, Mario L Marques-Piubelli, Francisco Vega Vazquez, Edwin R Parra Cuentas, Luisa M Solis-Soto, Wencai Ma, Jing Wang, Linda Claret, Barbara Averill, Karina Ibanez, Luis E Fayad, Christopher R Flowers, Michael R Green, R Eric Davis, Sattva S Neelapu, Nathan H Fowler, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an …

Effects Of A Liquefied Petroleum Gas Stove Intervention On Stillbirth, Congenital Anomalies And Neonatal Mortality: A Multi-Country Household Air Pollution Intervention Network Trial, Ashley Younger, Ashley Toenjes, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM

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 …

Β-Actin G342d As A Cause Of Nk Cell Deficiency Impairing Lytic Synapse Termination, Abigail E Reed, Jackeline Peraza, Frederique Van Den Haak, Evelyn R Hernandez, Richard A Gibbs, Ivan K Chinn, James R Lupski, Enrica Marchi, Ran Reshef, Bachir Alobeid, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Natural killer (NK) cell deficiency (NKD) occurs when an individual’s major clinical immunodeficiency derives from abnormal NK cells and is associated with several genetic etiologies. Three categories of β actin-related diseases with over 60 ACTB (β actin) variants have previously been identified, none with a distinct NK cell phenotype. An individual with mild developmental delay, macrothrombocytopenia, susceptibility to infections, molluscum, and EBV-associated lymphoma had functional NK cell deficiency for over a decade. A de novo ACTB variant encoding G342D β actin was identified and was consistent with the individual’s developmental and platelet phenotype. This novel variant also was found to …

The Evidence Of Electronic Cigarettes For Harm Reduction Is Not There, Manuel C Pacheco Gallego, Harold J Farber

Faculty, Staff and Students Publications

No abstract provided.

Resolution Of Severe Portopulmonary Hypertension With Inhaled Treprostinil And Liver Transplantation, Alex J Chang, Choon Hwa Goh

The Texas Heart Institute Journal

Portopulmonary hypertension is a rare condition with a poor prognosis. Prompt management is essential for liver transplantation eligibility, a potentially curative option. This report presents a case of severe portopulmonary hypertension that resolved with a conservative therapeutic regimen of tadalafil, macitentan, and inhaled treprostinil, which ultimately enabled successful liver transplantation. There was no recurrence of pulmonary hypertension after transplantation, and the patient was weaned off most pulmonary arterial hypertension therapies. This case report is the first to provide evidence that inhaled treprostinil is a safe and effective alternative to continuous intravenous prostacyclins in portopulmonary hypertension.