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Thomas Jefferson University

2024

Humans

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Full-Text Articles in Medicine and Health Sciences

The Janus Kinase 1 Is Critical For Pancreatic Cancer Initiation And Progression, Hridaya Shrestha, Patrick Rädler, Rayane Dennaoui, Madison Wicker, Nirakar Rajbhandari, Yunguang Sun, Amy Peck, Kerry Vistisen, Aleata Triplett, Rafic Beydoun, Esta Sterneck, Dieter Saur, Hallgeir Rui, Kay-Uwe Wagner May 2024

The Janus Kinase 1 Is Critical For Pancreatic Cancer Initiation And Progression, Hridaya Shrestha, Patrick Rädler, Rayane Dennaoui, Madison Wicker, Nirakar Rajbhandari, Yunguang Sun, Amy Peck, Kerry Vistisen, Aleata Triplett, Rafic Beydoun, Esta Sterneck, Dieter Saur, Hallgeir Rui, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRASG12D-induced pancreatic tumors, and we establish that JAK1 is essential for the constitutive activation of STAT3, whose activation is a prominent characteristic of PDAC. We identify CCAAT/enhancer binding protein δ (C/EBPδ) as a biologically relevant …


A Multi-Institutional Meningioma Mri Dataset For Automated Multi-Sequence Image Segmentation, Dominic Labella, Omaditya Khanna, Shan Mcburney-Lin, Ryan Mclean, Pierre Nedelec, Arif Rashid, Nourel Hoda Tahon, Talissa Altes, Ujjwal Baid, Radhika Bhalerao, Yaseen Dhemesh, Scott Floyd, Devon Godfrey, Fathi Hilal, Anastasia Janas, Anahita Kazerooni, Collin Kent, John Kirkpatrick, Florian Kofler, Kevin Leu, Nazanin Maleki, Bjoern Menze, Maxence Pajot, Zachary Reitman, Jeffrey Rudie, Rachit Saluja, Yury Velichko, Chunhao Wang, Pranav Warman, Nico Sollmann, David Diffley, Khanak Nandolia, Daniel Warren, Ali Hussain, John Pascal Fehringer, Yulia Bronstein, Lisa Deptula, Evan Stein, Mahsa Taherzadeh, Eduardo Portela De Oliveira, Aoife Haughey, Marinos Kontzialis, Luca Saba, Benjamin Turner, Melanie Brüßeler, Shehbaz Ansari, Athanasios Gkampenis, David Maximilian Weiss, Aya Mansour, Islam Shawali, Nikolay Yordanov, Joel Stein, Roula Hourani, Mohammed Yahya Moshebah, Ahmed Magdy Abouelatta, Tanvir Rizvi, Klara Willms, Dann Martin, Abdullah Okar, Gennaro D'Anna, Ahmed Taha, Yasaman Sharifi, Shahriar Faghani, Dominic Kite, Marco Pinho, Muhammad Ammar Haider, Michelle Alonso-Basanta, Javier Villanueva-Meyer, Andreas Rauschecker, Ayman Nada, Mariam Aboian, Adam Flanders, Spyridon Bakas, Evan Calabrese May 2024

A Multi-Institutional Meningioma Mri Dataset For Automated Multi-Sequence Image Segmentation, Dominic Labella, Omaditya Khanna, Shan Mcburney-Lin, Ryan Mclean, Pierre Nedelec, Arif Rashid, Nourel Hoda Tahon, Talissa Altes, Ujjwal Baid, Radhika Bhalerao, Yaseen Dhemesh, Scott Floyd, Devon Godfrey, Fathi Hilal, Anastasia Janas, Anahita Kazerooni, Collin Kent, John Kirkpatrick, Florian Kofler, Kevin Leu, Nazanin Maleki, Bjoern Menze, Maxence Pajot, Zachary Reitman, Jeffrey Rudie, Rachit Saluja, Yury Velichko, Chunhao Wang, Pranav Warman, Nico Sollmann, David Diffley, Khanak Nandolia, Daniel Warren, Ali Hussain, John Pascal Fehringer, Yulia Bronstein, Lisa Deptula, Evan Stein, Mahsa Taherzadeh, Eduardo Portela De Oliveira, Aoife Haughey, Marinos Kontzialis, Luca Saba, Benjamin Turner, Melanie Brüßeler, Shehbaz Ansari, Athanasios Gkampenis, David Maximilian Weiss, Aya Mansour, Islam Shawali, Nikolay Yordanov, Joel Stein, Roula Hourani, Mohammed Yahya Moshebah, Ahmed Magdy Abouelatta, Tanvir Rizvi, Klara Willms, Dann Martin, Abdullah Okar, Gennaro D'Anna, Ahmed Taha, Yasaman Sharifi, Shahriar Faghani, Dominic Kite, Marco Pinho, Muhammad Ammar Haider, Michelle Alonso-Basanta, Javier Villanueva-Meyer, Andreas Rauschecker, Ayman Nada, Mariam Aboian, Adam Flanders, Spyridon Bakas, Evan Calabrese

Department of Radiology Faculty Papers

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by …


Comprehensive Peripheral Blood Immunoprofiling Reveals Five Immunotypes With Immunotherapy Response Characteristics In Patients With Cancer, Daniiar Dyikanov, Aleksandr Zaitsev, Tatiana Vasileva, Iris Wang, Arseniy Sokolov, Evgenii Bolshakov, Alena Frank, Polina Turova, Olga Golubeva, Anna Gantseva, Anna Kamysheva, Polina Shpudeiko, Ilya Krauz, Mary Abdou, Madison Chasse, Tori Conroy, Nicholas Merriam, Julia Alesse, Noel English, Boris Shpak, Anna Shchetsova, Evgenii Tikhonov, Ivan Filatov, Anastasia Radko, Anastasiia Bolshakova, Anastasia Kachalova, Nika Lugovykh, Andrey Bulahov, Anastasiia Kilina, Syimyk Asanbekov, Irina Zheleznyak, Pavel Skoptsov, Evgenia Alekseeva, Jennifer Johnson, Joseph Curry, Alban Linnenbach, Andrew South, Enjun Yang, Kirill Morozov, Anastasiya Terenteva, Lira Nigmatullina, Dmitry Fastovetz, Anatoly Bobe, Linda Balabanian, Krystle Nomie, Sheila Yong, Christopher Davitt, Alexander Ryabykh, Olga Kudryashova, Cagdas Tazearslan, Alexander Bagaev, Nathan Fowler, Adam Luginbuhl, Ravshan Ataullakhanov, Michael Goldberg May 2024

Comprehensive Peripheral Blood Immunoprofiling Reveals Five Immunotypes With Immunotherapy Response Characteristics In Patients With Cancer, Daniiar Dyikanov, Aleksandr Zaitsev, Tatiana Vasileva, Iris Wang, Arseniy Sokolov, Evgenii Bolshakov, Alena Frank, Polina Turova, Olga Golubeva, Anna Gantseva, Anna Kamysheva, Polina Shpudeiko, Ilya Krauz, Mary Abdou, Madison Chasse, Tori Conroy, Nicholas Merriam, Julia Alesse, Noel English, Boris Shpak, Anna Shchetsova, Evgenii Tikhonov, Ivan Filatov, Anastasia Radko, Anastasiia Bolshakova, Anastasia Kachalova, Nika Lugovykh, Andrey Bulahov, Anastasiia Kilina, Syimyk Asanbekov, Irina Zheleznyak, Pavel Skoptsov, Evgenia Alekseeva, Jennifer Johnson, Joseph Curry, Alban Linnenbach, Andrew South, Enjun Yang, Kirill Morozov, Anastasiya Terenteva, Lira Nigmatullina, Dmitry Fastovetz, Anatoly Bobe, Linda Balabanian, Krystle Nomie, Sheila Yong, Christopher Davitt, Alexander Ryabykh, Olga Kudryashova, Cagdas Tazearslan, Alexander Bagaev, Nathan Fowler, Adam Luginbuhl, Ravshan Ataullakhanov, Michael Goldberg

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based …


A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki May 2024

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …


Prevalence Of Cardiovascular Conditions After Traumatic Brain Injury: A Comparison Between The Traumatic Brain Injury Model Systems And The National Health And Nutrition Examination Survey, Shanti Pinto, Bhaskar Thakur, Raj Kumar, Amanda Rabinowitz, Ross Zafonte, William C Walker, Kan Ding, Simon Driver, Umesh Venkatesan, Gilbert Moralez, Kathleen Bell May 2024

Prevalence Of Cardiovascular Conditions After Traumatic Brain Injury: A Comparison Between The Traumatic Brain Injury Model Systems And The National Health And Nutrition Examination Survey, Shanti Pinto, Bhaskar Thakur, Raj Kumar, Amanda Rabinowitz, Ross Zafonte, William C Walker, Kan Ding, Simon Driver, Umesh Venkatesan, Gilbert Moralez, Kathleen Bell

Department of Rehabilitation Medicine Faculty Papers

BACKGROUND: The purpose of this study is to compare the prevalence of self-reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity-matched control cohort.

METHODS AND RESULTS: A cross-sectional study described self-reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed-effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity-score matching based on age, sex, …


Integrated Transcriptomics And Histopathology Approach Identifies A Subset Of Rejected Donor Livers With Potential Suitability For Transplantation, Ankita Srivastava, Alexandra Manchel, John Waters, Manju Ambelil, Benjamin K. Barnhart, Jan B. Hoek, Ashesh P. Shah, Rajanikanth Vadigepalli May 2024

Integrated Transcriptomics And Histopathology Approach Identifies A Subset Of Rejected Donor Livers With Potential Suitability For Transplantation, Ankita Srivastava, Alexandra Manchel, John Waters, Manju Ambelil, Benjamin K. Barnhart, Jan B. Hoek, Ashesh P. Shah, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).

RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, …


Travel-Time Disparities In Access To Proton Beam Therapy For Cancer Treatment, Todd Burus, Alexander Vanhelene, Michael Rooney, Krystle Lang Kuhs, W. Jay Christian, Christopher Mcnair, Sanjay Mishra, Arnold Paulino, Grace Smith, Steven Frank, Jeremy Warner May 2024

Travel-Time Disparities In Access To Proton Beam Therapy For Cancer Treatment, Todd Burus, Alexander Vanhelene, Michael Rooney, Krystle Lang Kuhs, W. Jay Christian, Christopher Mcnair, Sanjay Mishra, Arnold Paulino, Grace Smith, Steven Frank, Jeremy Warner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

IMPORTANCE: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials.

OBJECTIVE: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study analyzed travel times to proton facilities in …


Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza May 2024

Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza

Division of Cardiology Faculty Papers

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.

MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and …


The American Thoracic Society Research Program: Twenty Years Of Driving Discovery In Respiratory Medicine, Kamran Atabai, M. Safwan Badr, Jack Costello, Karen Ridge, Sharon Rounds, Michelle Turenne, Eric White, Jesse Roman May 2024

The American Thoracic Society Research Program: Twenty Years Of Driving Discovery In Respiratory Medicine, Kamran Atabai, M. Safwan Badr, Jack Costello, Karen Ridge, Sharon Rounds, Michelle Turenne, Eric White, Jesse Roman

Division of Pulmonary and Critical Care Medicine Faculty Papers

No abstract provided.


Expanding The Access To Kidney Transplantation: Strategies For Kidney Transplant Programs, Angie Nishio Lucar, Ankita Patel, Shikha Mehta, Anju Yadav, Mona Doshi, Megan Urbanski, Beatrice Concepcion, Neeraj Singh, M. Lee Sanders, Arpita Basu, Jessica Harding, Ana Rossi, Oluwafisayo Adebiyi, Milagros Samaniego-Picota, Kenneth Woodside, Ronald Parsons May 2024

Expanding The Access To Kidney Transplantation: Strategies For Kidney Transplant Programs, Angie Nishio Lucar, Ankita Patel, Shikha Mehta, Anju Yadav, Mona Doshi, Megan Urbanski, Beatrice Concepcion, Neeraj Singh, M. Lee Sanders, Arpita Basu, Jessica Harding, Ana Rossi, Oluwafisayo Adebiyi, Milagros Samaniego-Picota, Kenneth Woodside, Ronald Parsons

Department of Medicine Faculty Papers

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such …


Post-Covid Small Fiber Neuropathy, Implications Of Innate Immunity, And Challenges On Ivig Therapy, Marinos Dalakas May 2024

Post-Covid Small Fiber Neuropathy, Implications Of Innate Immunity, And Challenges On Ivig Therapy, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.


Parents' Perceptions Of Eye-Gaze Technology Use By Children With Complex Communication Needs, Sandra Masayko, Joy Mcgowan, Namrata Grampurohit May 2024

Parents' Perceptions Of Eye-Gaze Technology Use By Children With Complex Communication Needs, Sandra Masayko, Joy Mcgowan, Namrata Grampurohit

Department of Occupational Therapy Faculty Papers

PURPOSE: Some preschool students with complex communication needs explore eye-gaze computer technology (EGCT) and adopt computer-based augmentative and alternative communication (AAC). The objective of this study was to follow preschool explorers of EGCT who are now school aged to describe the children's use of technology and parents' perceptions of its utility for communication, participation, or leisure.

METHOD: Ten parents completed survey questions by Internet and phone and reported their perceptions of nine children's effectiveness in the use and acceptance of AAC and the support they received in implementing technology. The results are reported as a descriptive study.

RESULTS: All children …


Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo Apr 2024

Decorin Suppresses Tumor Lymphangiogenesis: A Mechanism To Curtail Cancer Progression, Dipon K. Mondal, Christopher Xie, Gabriel J. Pascal, Simone Buraschi, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, …


Family Physicians And Menstrual Care: An Analysis Of Cera 2023, Allison Casola, Olivia Rea, Tiffany Ho Apr 2024

Family Physicians And Menstrual Care: An Analysis Of Cera 2023, Allison Casola, Olivia Rea, Tiffany Ho

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Menstrual health is an important indicator of overall health and has large impacts on quality of life. Despite number and impact, discussion of menstruation remains largely taboo within health care. Patients and physicians are not engaging in regular, meaningful discussions on menstruation. Family physicians, as primary care providers, can facilitate these important conversations.

OBJECTIVES: We sought to understand the profile of menstrual care providing family physicians and assessed physician comfort, knowledge, training, and perceived importance regarding menstrual care.

DESIGN/METHODS: This is a cross-sectional analysis of the 2022 Council of Academic Family Medicine Educational Research Alliance survey. The survey included …


Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu Apr 2024

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …


Comprehensive Guidance For The Prevention Of Periprosthetic Joint Infection After Total Joint Arthroplasty And Pitfalls In The Prevention, Javad Parvizi, Yonghan Cha, Emanuele Chisari, Kangbaek Kim, Kyung-Hoi Koo Apr 2024

Comprehensive Guidance For The Prevention Of Periprosthetic Joint Infection After Total Joint Arthroplasty And Pitfalls In The Prevention, Javad Parvizi, Yonghan Cha, Emanuele Chisari, Kangbaek Kim, Kyung-Hoi Koo

Rothman Institute Faculty Papers

Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA. With the increasing volume …


Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester Apr 2024

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …


The Dual-Targeted Fusion Inhibitor Clofazimine Binds To The S2 Segment Of The Sars-Cov-2 Spike Protein, Matthew Freidel, Pratiti Vakhariya, Shalinder Sardarni, Roger Armen Apr 2024

The Dual-Targeted Fusion Inhibitor Clofazimine Binds To The S2 Segment Of The Sars-Cov-2 Spike Protein, Matthew Freidel, Pratiti Vakhariya, Shalinder Sardarni, Roger Armen

College of Pharmacy Faculty Papers

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the …


Perspectives From Patients With Chronic Lung Disease On A Telehealth-Facilitated Integrated Palliative Care Model: A Qualitative Content Analysis Study, Jeannette Kates, Carrie Tompkins Stricker, Kristin L. Rising, Alexzandra Gentsch, Ellen Solomon, Victoria Powers, Venise J. Salcedo, Brooke Worster Apr 2024

Perspectives From Patients With Chronic Lung Disease On A Telehealth-Facilitated Integrated Palliative Care Model: A Qualitative Content Analysis Study, Jeannette Kates, Carrie Tompkins Stricker, Kristin L. Rising, Alexzandra Gentsch, Ellen Solomon, Victoria Powers, Venise J. Salcedo, Brooke Worster

Department of Medicine Faculty Papers

BACKGROUND: Chronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing.

METHODS: For this qualitative …


Dismantling Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among The Pwud Community In Philadelphia, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Rachel Holbert, Jason Zambrano, Daljinder Bhangoo, Chari Cohen, Richard W. Hass, Amy Jessop Apr 2024

Dismantling Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among The Pwud Community In Philadelphia, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Rachel Holbert, Jason Zambrano, Daljinder Bhangoo, Chari Cohen, Richard W. Hass, Amy Jessop

College of Population Health Faculty Papers

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher's exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) did not have hepatitis B immunity, 52.6% had been vaccinated against …


Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson Apr 2024

Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% …


Discussing Menstrual Health In Family Medicine, Allison Casola, Alice Renaud, Ashwini Kamath Mulki Apr 2024

Discussing Menstrual Health In Family Medicine, Allison Casola, Alice Renaud, Ashwini Kamath Mulki

Department of Family & Community Medicine Faculty Papers

No abstract provided.


Occupational Therapy Students’ Perceptions Of Their Experience In A Role-Emerging Level Ii Fieldwork Within Higher Education Student Services, Marie-Christine Potvin, Alexis Morales, Erin West, Mika Kalimi, Jeanne M Coviello Apr 2024

Occupational Therapy Students’ Perceptions Of Their Experience In A Role-Emerging Level Ii Fieldwork Within Higher Education Student Services, Marie-Christine Potvin, Alexis Morales, Erin West, Mika Kalimi, Jeanne M Coviello

Department of Occupational Therapy Faculty Papers

BACKGROUND: Role-emerging settings - those where occupational therapy (OT) services have not traditionally been provided - are common sites for practice placements of entry-level occupational therapy students. A growing body of literature has attempted to determine the value and drawbacks of such practice placements on the professional preparedness of OT students with mixed findings. Benefits have been identified, including increased cultural understanding, advocacy, creativity, initiative, and problem-solving skills. However, OT students have been reported to perceive such placement as limiting their professional growth and preparedness to practice compared to traditional placements.

METHODS: A phenomenological study was conducted seeking the perceptions …


Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz Apr 2024

Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …


Swiss Cheese Heart: A Tale Of Multiple Valve Perforations, Hussam Al Hennawi, Shayan I. Khan, Aamna Khan, Usama Sadiq, Sung-Hae Cho Apr 2024

Swiss Cheese Heart: A Tale Of Multiple Valve Perforations, Hussam Al Hennawi, Shayan I. Khan, Aamna Khan, Usama Sadiq, Sung-Hae Cho

Abington Jefferson Health Papers

Gerbode defect, an anomalous connection between the left ventricle and right atrium, is often congenital but can be acquired or iatrogenically formed. We present an exceedingly rare case of this defect associated with multiple valve perforation in an otherwise healthy patient with bicuspid aortic valve and endocarditis.


Role Of Mechanoregulation In Mast Cell-Mediated Immune Inflammation Of The Smooth Muscle In The Pathophysiology Of Esophageal Motility Disorders, Raj Goyal, Satish Rattan Apr 2024

Role Of Mechanoregulation In Mast Cell-Mediated Immune Inflammation Of The Smooth Muscle In The Pathophysiology Of Esophageal Motility Disorders, Raj Goyal, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that …


Delayed Onset Of Neonatal Compartment Syndrome Associated With Compound Fetal Presentation, Nicholas Manini, Hayato Unno Apr 2024

Delayed Onset Of Neonatal Compartment Syndrome Associated With Compound Fetal Presentation, Nicholas Manini, Hayato Unno

Department of Medicine Faculty Papers

Neonatal compartment syndrome, although rare, has a classic presentation with sentinel skin findings and development of swelling, erythema, and tenderness of the affected extremity. Neonatal compartment syndrome requires prompt surgical intervention to preserve the affected limb and ensure its normal growth and development. Our patient was born at term via vaginal delivery complicated by a compound presentation involving the left upper extremity. No physical exam abnormalities were noted at birth, but she developed signs of neonatal compartment syndrome by 15 h of life. She was surgically treated at 22 h of life and recovered well. At one year of age, …


Ic3d Classification Of Corneal Dystrophies-Edition 3, Jayne Weiss, Christopher Rapuano, Berthold Seitz, Massimo Busin, Tero Kivelä, Nacim Bouheraoua, Cecilie Bredrup, Ken Nischal, Harshvardhan Chawla, Vincent Borderie, Kenneth Kenyon, Eung Kweon Kim, Hans Ulrik Møller, Francis Munier, Tim Berger, Walter Lisch Apr 2024

Ic3d Classification Of Corneal Dystrophies-Edition 3, Jayne Weiss, Christopher Rapuano, Berthold Seitz, Massimo Busin, Tero Kivelä, Nacim Bouheraoua, Cecilie Bredrup, Ken Nischal, Harshvardhan Chawla, Vincent Borderie, Kenneth Kenyon, Eung Kweon Kim, Hans Ulrik Møller, Francis Munier, Tim Berger, Walter Lisch

Wills Eye Hospital Papers

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature.

METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)].

RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( …


Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer Mar 2024

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

No abstract provided.


The Psychological Burden Of Nmosd - A Mixed Method Study Of Patients And Caregivers, Darcy C. Esiason, Nicole Ciesinski, Chelsi N. Nurse, Wendy Erler, Tom Hattrich, Ankita Deshpande, C. Virginia O'Hayer Mar 2024

The Psychological Burden Of Nmosd - A Mixed Method Study Of Patients And Caregivers, Darcy C. Esiason, Nicole Ciesinski, Chelsi N. Nurse, Wendy Erler, Tom Hattrich, Ankita Deshpande, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system with common symptoms of rapid onset of eye pain, loss of vision, neck/back pain, paralysis, bowel and bladder dysfunction and heat sensitivity. The rare, unpredictable, and debilitating nature of NMOSD constitutes a unique psychological burden for patients and their caregivers, the specific nature and extent of which is not yet known. This mixed methods study, informed by both quantitative and qualitative data collected via self-report measures, focus groups, and in-depth interviews, aims to investigate and understand the psychological burden of patients with NMOSD and their caregiver/loved …