Medicine and Health Sciences Commons^™

A Path Towards Digital Equity

Thomas Jefferson University Research Magazine

Telemedicine is a vital tool in health care, but it’s leaving some patients behind. Jefferson researchers are on a mission to improve ‘digital readiness’ in under-resourced communities to bridge inequities.

Inflecting The Narrative On African Studies

Thomas Jefferson University Research Magazine

Inflection points can be powerful events. They can prompt an individual to take on a new career challenge. And on occasion, that individual’s decision can redound to the benefit of thousands of others. Such may be the case for Marcella McCoy-Deh, PhD, associate professor of American Studies and director of the Philadelphia University Honors Institute.

A Journey Of Adaptation

Thomas Jefferson University Research Magazine

Consider Haloferax volcanii, a single celled organism that thrives in extreme conditions such as the very salty Dead Sea. Scientists study it for clues about potential life on Mars and about how organisms may adapt to Earth’s changing climate. Much like the organism she studies, H. volcanii researcher Manuela Tripepi, PhD, is an expert at adapting to challenging situations.

Covid Briefs

Thomas Jefferson University Research Magazine

• Intellectual Disability a High Risk for COVID-19 Death
• Design Solutions for COVID-19 Problems
• The Secret Sauce in COVID-19 Vaccines
• At Home with Dementia during the Pandemic
• Predicting the Severe Cases of COVID-19

Enveloping Buildings In Textiles

Thomas Jefferson University Research Magazine

There are myriad elements that determine how well a building functions. One of the most important and complex is the design and composition of its envelope. Similar to the human skin, the building envelope is the boundary between interior and exterior, and it has multiple functions: protecting the indoor environment, facilitating climate control and reducing the building’s energy consumption.

Learning From Drowsy Flies

Thomas Jefferson University Research Magazine

Who knew that fruit flies slept—or that humans might benefit from studying their sleep? Kyunghee Koh, PhD, does. The associate professor of Neuroscience uses fruit flies (Drosophila melanogaster) to identify the cellular and molecular mechanisms underpinning sleep. Two of her lab’s recent studies offer results that are both interesting and potentially far-reaching

Cancer Prediction Model Misses High-Risk Black Patients

Thomas Jefferson University Research Magazine

Black men are more likely to die from lung cancer than persons of any other racial or ethnic group. A new study suggests that better detection could reduce that disparity.

Antitrust Laws Don't Hinder Foreign Investment

Thomas Jefferson University Research Magazine

Using data on the period from 1970 to 2019 from the World Bank’s World Development Indicators, this study considered the question of whether anti-trust laws encourage or diminish foreign investment in developing and transition countries

Bursts Of Power

Thomas Jefferson University Research Magazine

Mitochondria fire oxidants to communicate with organelles nearby, a communication that could be important in various diseases.

Reaching Across The Globe And To The Stars

Thomas Jefferson University Research Magazine

From maternal health to science in space, Jefferson’s global initiatives are attacking pressing problems through connected learning and investigation.

Research blooms in an interconnected world. Research that is open to the rich knowledge, experience and culture of collaborators across the globe is stronger for it. Thomas Jefferson University is building international partnerships to tackle health disparities and innovations in medicine, and to broaden access and opportunities that have lasting impact. Read about Jefferson’s global footprint.

Editorial: Glia-Mediated Neurotoxicity: Uncovering The Molecular Mechanisms, Amit K Srivastava, Barbara Lukomska, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

No abstract provided.

Predictive Factors And Outcomes For Ibrutinib In Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Sayan Mullick Chowdhury, Lauren Shea, Tamara K Moyo, Nishitha Reddy, Julia Sheets, David M Weiner, Praveen Ramakrishnan Geethakumari, Malathi Kandarpa, Ximena Jordan Bruno, Colin Thomas, Michael C Churnetski, Andrew Hsu, Luke Zurbriggen, Cherie Tan, Kathryn Lindsey, Joseph Maakaron, Paolo F Caimi, Pallawi Torka, Celeste Bello, Sabarish Ayyappan, Reem Karmali, Seo-Hyun Kim, Anna Kress, Shalin Kothari, Yazeed Sawalha, Beth Christian, Kevin A David, Irl Brian Greenwell, Murali Janakiram, Vaishalee P Kenkre, Adam J Olszewski, Jonathon B Cohen, Neil D. Palmisiano, Elvira Umyarova, Ryan A Wilcox, Farrukh T Awan, Juan Pablo Alderuccio, Stefan K Barta, Natalie S Grover, Nilanjan Ghosh, Nancy L Bartlett, Alex F Herrera, Geoffrey Shouse

Department of Medicine Faculty Papers

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% …

Echocardiographic Predictors Of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: A Systematic Review And Meta-Analysis, Muhammad Umer Siddiqui, Youssef Yaacoub, Heidi-Anne Hanson, Joey Junarta, Ahmed K Pasha, Mahek Shah

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy.

OBJECTIVE: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy.

METHODS: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures …

Cryo-Em Structure Of The Human Kv3.1 Channel Reveals Gating Control By The Cytoplasmic T1 Domain, Gamma Chi, Qiansheng Liang, Akshay Sridhar, John B Cowgill, Kasim Sader, Mazdak Radjainia, Pu Qian, Pablo Castro-Hartmann, Shayla Venkaya, Nanki Kaur Singh, Gavin Mckinley, Alejandra Fernandez-Cid, Shubhashish M M Mukhopadhyay, Nicola A Burgess-Brown, Lucie Delemotte, Manuel Covarrubias, Katharina L Dürr

Department of Neuroscience Faculty Papers

Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and …

Reports Of Adverse Events Associated With Use Of Novel Psychoactive Substances, 2017-2020: A Review, Amanda L A Mohr, Barry K Logan, Melissa F Fogarty, Alex J Krotulski, Donna M Papsun, Sherri L Kacinko, Marilyn A Huestis, Jeri D Ropero-Miller

Institute of Emerging Health Professions Faculty Papers

An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed …

Racial Disparities In Hepatitis B Birth Dose In The Washington Metropolitan Region, 2018-2020., Hee-Soon Juon, Donna T Sheler, Jane Pan, Daisy Le, Y Tony Yang

Department of Medical Oncology Faculty Papers

Hepatitis B vaccination protects newborns from contracting the hepatitis B virus that may lead to chronic infection, liver failure, or death. Trends and racial differences in the administration of the hepatitis B (HepB) birth dose in 2018-2020 were examined in the targeted region. A retrospective analysis of electronic birth dose vaccination data of newborns in 2018-2020 was performed. Birth data from six birthing facilities and home delivery records were obtained from the DC Health Department Vital Statistics Division. This data represented 40,269 newborns and included the mother's race and ethnicity, health insurance type, birthing facility, and administration of the HepB …

Addressing The Gap In Data Communication From Home Health Care To Primary Care During Care Transitions: Completeness Of An Interoperability Data Standard, Paulina Sockolow, Edgar Y Chou, Subin Park

Department of Medicine Faculty Papers

In a future where home health care is no longer an information silo, patient information will be communicated along transitions in care to improve care. Evidence-based practice in the United States supports home health care patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. We sought to identify a parsimonious set of home health care data to be communicated to primary care for the post-hospitalization visit. Anticipating electronic dataset communication, we investigated the completeness of the international reference terminology, Logical Observation Identifiers Names and Codes (LOINC), for coverage of the …

Pruritic Annular Erythematous Eruption After Receiving The Covid-19 Vaccine, Devon E. Cross, James Garritano, Amanda E. Zubek, Alicia J. Little

COVID-19 Papers, Posters, and Presentations

No abstract provided.

Novel Mechanisms For Post-Transplant Maintenance Therapy In Acute Myeloid Leukemia, Steven A Manobianco, Tara Rakiewicz, Lindsay Wilde, Neil D Palmisiano

Department of Medical Oncology Faculty Papers

Allogeneic stem cell transplantation has improved survival for patients with acute myeloid leukemia (AML), especially for patients with disease at high risk of relapse. However, relapse remains the most common cause of treatment failure and death in the post-transplant period. Maintenance therapy, an extended course of treatment after achieving remission to reduce the rate of relapse, is an important component of the treatment of various hematologic malignancies; however, its role in the treatment of AML is far less well-defined. Recently, there has been significant interest in the use of novel therapeutic agents as maintenance therapy after allogeneic stem cell transplant, …

Γ-Secretase Promotes Drosophila Postsynaptic Development Through The Cleavage Of A Wnt Receptor, Lucas J Restrepo, Alison T Depew, Elizabeth R Moese, Stephen R Tymanskyj, Michael J Parisi, Michael A Aimino, Juan Carlos Duhart, Hong Fei, Timothy J Mosca

Farber Institute for Neuroscience Faculty Papers

Developing synapses mature through the recruitment of specific proteins that stabilize presynaptic and postsynaptic structure and function. Wnt ligands signaling via Frizzled (Fz) receptors play many crucial roles in neuronal and synaptic development, but whether and how Wnt and Fz influence synaptic maturation is incompletely understood. Here, we show that Fz2 receptor cleavage via the γ-secretase complex is required for postsynaptic development and maturation. In the absence of γ-secretase, Drosophila neuromuscular synapses fail to recruit postsynaptic scaffolding and cytoskeletal proteins, leading to behavioral deficits. Introducing presenilin mutations linked to familial early-onset Alzheimer's disease into flies leads to synaptic maturation phenotypes …

Social Determinants Of Health In Pulmonary Arterial Hypertension Patients In The United States: Clinician Perspective And Health Policy Implications, Vijay R. Nadipelli, Jean M. Elwing, Willie H. Oglesby, Karim El-Kersh

College of Population Health Faculty Papers

Social determinants of health (SDoH) can impact the vulnerable pulmonary arterial hypertension (PAH) population, especially during the COVID-19 pandemic. Providers' understanding of SDoH at the point of care and their impact is unknown. We conducted semi-structured virtual interviews with US clinicians at 17 pulmonary hypertension (PH) centers and one patient advocate from the Pulmonary Hypertension Association. We sought participants' perspective on SDoH in PAH and their impact. Transcripts were developed and analyzed for key themes to assess potential policy implications. Participants served a large PAH population and demonstrated high awareness of SDoH and its impact on treatment and outcomes. They …

In Vivo Determination Of The Human Corneal Elastic Modulus Using Vibrational Optical Coherence Tomography, Marcos A. Crespo, Hiram J. Jimenez, Tanmay Deshmukh, Jose S. Pulido, Ahmed Saeed Saad, Frederick H Silver, Dominick A Benedetto, Christopher J Rapuano, Zeba Syed

Wills Eye Hospital Papers

Purpose: To determine the in vivo elastic modulus of the human cornea using vibrational optical coherence tomography (VOCT).

Methods: Vibrational analysis coupled with optical coherence tomography (OCT) was used to obtain the resonant frequency (RF) and elastic modulus of corneal structural components. VOCT corneal thickness values were measured using OCT images and correlated with corneal thickness determined with Pentacam (Oculus, Wetzlar, Germany). Moduli were obtained at two locations: central cornea (CC) and inferior cornea (IC). Measurements were obtained with and without anesthetic eye drops to assess their effect on the modulus measurements.

Results: VOCT thickness values correlated positively (R2 = …

Interleukin-8 Produced From Cancer-Associated Fibroblasts Suppresses Proliferation Of The Ocuch-Lm1 Cancer Cell Line, Ryota Tanaka, Kenjiro Kimura, Shimpei Eguchi, Go Ohira, Shogo Tanaka, Ryosuke Amano, Hiroaki Tanaka, Masakazu Yashiro, Masaichi Ohira, Shoji Kubo

Department of Medical Oncology Faculty Papers

Background: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort.

Methods: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines …

Prmt5 Activates Akt Via Methylation To Promote Tumor Metastasis., Lei Huang, Xiao-Ou Zhang, Esteban J Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P Cavaretta, Gang Wang, Lei Zhang, Jason M Shohet, Mary M. Lee, Qiong Wu

Department of Pediatrics Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) is the primary methyltransferase generating symmetric-dimethyl-arginine marks on histone and non-histone proteins. PRMT5 dysregulation is implicated in multiple oncogenic processes. Here, we report that PRMT5-mediated methylation of protein kinase B (AKT) is required for its subsequent phosphorylation at Thr308 and Ser473. Moreover, pharmacologic or genetic inhibition of PRMT5 abolishes AKT1 arginine 15 methylation, thereby preventing AKT1 translocation to the plasma membrane and subsequent recruitment of its upstream activating kinases PDK1 and mTOR2. We show that PRMT5/AKT signaling controls the expression of the epithelial-mesenchymal-transition transcription factors ZEB1, SNAIL, and TWIST1. PRMT5 inhibition significantly attenuates primary tumor …

Antibody Response To Sars-Cov-2 Vaccination In Patients With Lymphoproliferative Disorders And Plasma Cell Dyscrasias: Anti-Lymphoma Therapy As A Predictive Biomarker Of Response To Vaccination, Carol Gung, Regina Mcguire, Mercy George, Abdullateef Abdulkareem, Katherine A Belden, Pierluigi Porcu, Ubaldo Martinez-Outschoorn, Adam F Binder, Inna Chervenova, Onder Alpdogan

Department of Medical Oncology Faculty Papers

We retrospectively analyzed SARS-CoV-2 vaccination antibody responses in a cohort of 273 patients with lymphoproliferative disorders or plasma cell dyscrasias who were seen at a single tertiary cancer center. Semi-quantitative anti-spike protein serologic testing was performed with enzyme immunoassay method. We found that the antibody response rate to SARS-CoV-2 vaccination was 74.7% in our patient cohort with no difference based on gender, age or race. The highest response rate was found in patients with Multiple Myeloma (MM) (95.5%). The response rates found in Diffuse Large B-Cell Lymphoma (DLBCL), Chronic Lymphocytic Leukemia (CLL), and Low-Grade Non-Hodgkin Lymphoma (LG-NHL) were 73.2%, 61.5% …

Birth Length Is The Strongest Predictor Of Linear Growth Status And Stunting In The First 2 Years Of Life After A Preconception Maternal Nutrition Intervention: The Children Of The Women First Trial, Nancy F Krebs, K Michael Hambidge, Jamie L Westcott, Ana L Garcés, Lester Figueroa, Antoinette K Tshefu, Adrien L Lokangaka, Shivaprasad S Goudar, Sangappa M Dhaded, Sarah Saleem, Sumera Aziz Ali, Melissa S Bauserman, Richard J Derman, Robert L Goldenberg, Abhik Das, Dhuly Chowdhury

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3).

OBJECTIVES: We evaluated intervention effects on infants' longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo.

METHODS: Infants' anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic …

Neuromuscular Junction Pathology Is Correlated With Differential Motor Unit Vulnerability In Spinal And Bulbar Muscular Atrophy, Elana Molotsky, Y Liu, Andrew P Lieberman, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is an X-linked, neuromuscular neurodegenerative disease for which there is no cure. The disease is characterized by a selective decrease in fast-muscle power (e.g., tongue pressure, grip strength) accompanied by a selective loss of fast-twitch muscle fibers. However, the relationship between neuromuscular junction (NMJ) pathology and fast-twitch motor unit vulnerability has yet to be explored. In this study, we used a cross-model comparison of two mouse models of SBMA to evaluate neuromuscular junction pathology, glycolytic-to-oxidative fiber-type switching, and cytoskeletal alterations in pre- and postsynaptic termini of tibialis anterior (TA), gastrocnemius, and soleus hindlimb muscles. …

Reduced Rates Of Post-Transplant Recurrent Hepatocellular Carcinoma In Non-Alcoholic Steatohepatitis: A Propensity Score Matched Analysis, Ryan Lamm, Peter J Altshuler, Keyur Patel, Osama Shaheen, Angel Paulo Amante, Jesse Civan, Warren Maley, Adam Frank, Carlo Ramirez, Jaime Glorioso, Ashesh Shah, Hien Dang, Adam S Bodzin

Department of Surgery Faculty Papers

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC—1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years …

Breaking Barriers To Breast Reconstruction Among Socioeconomically Disadvantaged Patients At A Large Safety-Net Hospital, Anna E Meade, Samantha M Cummins, Jordyn T Farewell, Sofia Duque, Sydney K Mulqueen, Ashleigh Chuah, Andrew Y Zhang

Department of Medicine Faculty Papers

Socioeconomic disparities remain prevalent among those who undergo breast reconstruction. At our institution, patients must meet certain criteria to become eligible for breast reconstruction. The purpose of this study was to determine the impact of socioeconomic factors on breast reconstruction eligibility, enrollment, choice, and completion at our large safety-net institution.

Methods: A retrospective chart review of patients who underwent partial or total mastectomy at a large safety-net hospital from 2016 to 2019 was completed. Surgical and demographic data were compared across varying socioeconomic factors.

Results: A total of 645 patients were included in the study. More patients of a racial …

Regulating Phase Transition In Neurodegenerative Diseases By Nuclear Import Receptors, Amandeep Girdhar, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with a low-complexity prion-like domain (PLD) can undergo aberrant phase transitions and have been implicated in neurodegenerative diseases such as ALS and FTD. Several nuclear RBPs mislocalize to cytoplasmic inclusions in disease conditions. Impairment in nucleocytoplasmic transport is another major event observed in ageing and in neurodegenerative disorders. Nuclear import receptors (NIRs) regulate the nucleocytoplasmic transport of different RBPs bearing a nuclear localization signal by restoring their nuclear localization. NIRs can also specifically dissolve or prevent the aggregation and liquid–liquid phase separation of wild-type or disease-linked mutant RBPs, due to their chaperoning activity. This review focuses on …