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Articles 2551 - 2580 of 14909

Full-Text Articles in Medicine and Health Sciences

Capa: Quality Control Testing Of Laboratory Plates, Div Galdi, Bryn Mallon Apr 2024

Capa: Quality Control Testing Of Laboratory Plates, Div Galdi, Bryn Mallon

JCHP Collaborative Capstone and Research Exchange

Abstract

The purpose of a Corrective and Preventive Action (CAPA) investigation is to identify and address errors, deviations, and compliance issues to ensure the integrity, reliability, and quality of research and biomanufacturing. In the biotech industry, where identifying and rectifying root causes of errors is key to ensuring quality data and preventing future errors, CAPA plays a crucial role. The Jefferson Biotechnology (JBT) lab was asked to investigate the sterility of a biotech supplier’s microbiological agar plates, when a client reported contamination in their agar plates, suspecting contamination prior to sleeve opening. By attempting to reproduce our client's results through …


Empowering Students With 5s Organizational Skills For Research Laboratory Optimization, Paula Mccourt, Phd Apr 2024

Empowering Students With 5s Organizational Skills For Research Laboratory Optimization, Paula Mccourt, Phd

JCHP Collaborative Capstone and Research Exchange

Abstract

5S (Sort, Set-in-order, Shine, Standardize and Sustain) is a cost-effective organizational methodology frequently employed by biotech research labs and biomanufacturing to streamline optimization of production. Educational research labs offer experiential learning opportunities and serve as ideal environments for implementing 5S principles within undergraduate and graduate biotechnology curricula. In the Jefferson Biotechnology Program, the newly updated “Lab Design and Stewardship (BT303/503)” lecture and laboratory course, now integrates the 5S methodology into biotech student skill development. Participants in the BT303/503 course are instructed to improve workspaces within the biotechnology laboratory to bolster safety, efficiency, and inventory and equipment management. Through a …


Retention Of Respiratory Therapists: A Systems Thinking Approach, Jerin G. Juby, Dmgt, Rrt Apr 2024

Retention Of Respiratory Therapists: A Systems Thinking Approach, Jerin G. Juby, Dmgt, Rrt

JCHP Collaborative Capstone and Research Exchange

Abstract

Respiratory therapists are an integral part of the healthcare workforce in the United States. The healthcare workforce shortage accelerated by the COVID global pandemic has impacted respiratory therapy departments across the nation, with organizations struggling to hire and retain staff. The prevailing approaches in combating this are linear in nature and do not consider the complexity of the system. This mode of thinking does not adequately consider the characteristics and influences of the containing system, the many elements within the problematic organizational system, or their interdependencies and interactions. This study frames retention as a complex system problem wherein organizations …


Evaluating Bone Fracture Healing Utilizing Novel Ultrasound Modes, X-Ray And Dual-Energy X-Ray Absorptiometry In A Rabbit Model, Priscilla Machado, Rachel Blackman, Ji-Bin Liu, Flemming Forsberg, Traci Fox Apr 2024

Evaluating Bone Fracture Healing Utilizing Novel Ultrasound Modes, X-Ray And Dual-Energy X-Ray Absorptiometry In A Rabbit Model, Priscilla Machado, Rachel Blackman, Ji-Bin Liu, Flemming Forsberg, Traci Fox

Department of Radiology Posters

Background and Purpose

Healing in bone fractures is a complex process involving local inflammation, angiogenesis (i.e., the creation of new blood vessels), and formation of a bone-building callus, all of which leads to returning the bone nearly to its pre-fracture state. This is the process in a bone where the fracture is clean and the fractured ends oppose each other. Five to 10 percent of fractures are described as non-union, which can lead to poor healing and long-term complications. The purpose of this study was to compare fracture healing in a rabbit model using x-ray, the traditional method for evaluating …


Biomedical Text Readability After Hypernym Substitution With Fine-Tuned Large Language Models, Karl Swanson, Shuhan He, Josh Calvano, David Chen, Talar Telvizian, Lawrence Jiang, Paul Chong, Jacob Schwell, Gin Mak, Jarone Lee Apr 2024

Biomedical Text Readability After Hypernym Substitution With Fine-Tuned Large Language Models, Karl Swanson, Shuhan He, Josh Calvano, David Chen, Talar Telvizian, Lawrence Jiang, Paul Chong, Jacob Schwell, Gin Mak, Jarone Lee

SKMC Student Presentations and Publications

The advent of patient access to complex medical information online has highlighted the need for simplification of biomedical text to improve patient understanding and engagement in taking ownership of their health. However, comprehension of biomedical text remains a difficult task due to the need for domain-specific expertise. We aimed to study the simplification of biomedical text via large language models (LLMs) commonly used for general natural language processing tasks involve text comprehension, summarization, generation, and prediction of new text from prompts. Specifically, we finetuned three variants of large language models to perform substitutions of complex words and word phrases in …


Relief In Gastrointestinal Symptoms With Medical Marijuana Over 1 Year, Matthew P. Wallingford, Erin L. Kelly, Allison Herens, Daniel Hanna, Emily Hajjar, Brooke Worster Apr 2024

Relief In Gastrointestinal Symptoms With Medical Marijuana Over 1 Year, Matthew P. Wallingford, Erin L. Kelly, Allison Herens, Daniel Hanna, Emily Hajjar, Brooke Worster

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Subjective improvement in gastrointestinal (GI) symptoms was assessed among patients using medical marijuana (MMJ).

METHODS: Participants completed surveys at 0 days, 30 days, 6 months, and 12 months with questions about the severity of their GI symptoms on a scale from 1 (mild) to 3 (severe).

RESULTS: In each survey, participants reported a significant decrease in GI symptom severity when using MMJ versus when not using MMJ (p < 0.05). The most common self-reported side effects from using MMJ were increased appetite (12-21.4%), fatigue (6-16.7%), anxiety (4-11.9%), cough (4-11.9%), headache (6-7.9%), and dry mouth (4-7.1%).

CONCLUSION: In patients with chronic GI symptoms, MMJ may provide persistent symptom severity improvement. Limited product availability and mild to moderate side effects are factors to consider before trialing MMJ.


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% …


Mcl-1 Mediates Intrinsic Resistance To Raf Inhibitors In Mutant Braf Papillary Thyroid Carcinoma, Maria Cavallo, Jacob Yo, Kayla Gallant, Camille Cunanan, Amirali Amirfallah, Marzieh Daniali, Alyssa Sanders, Andrew Aplin, Edmund Pribitkin, Edward Hartsough Apr 2024

Mcl-1 Mediates Intrinsic Resistance To Raf Inhibitors In Mutant Braf Papillary Thyroid Carcinoma, Maria Cavallo, Jacob Yo, Kayla Gallant, Camille Cunanan, Amirali Amirfallah, Marzieh Daniali, Alyssa Sanders, Andrew Aplin, Edmund Pribitkin, Edward Hartsough

Kimmel Cancer Center Faculty Papers

Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response …


Coronary Microvascular Dysfunction In Childhood: An Emerging Pathological Entity And Its Clinical Implications, Takeshi Tsuda, Gina Patel Apr 2024

Coronary Microvascular Dysfunction In Childhood: An Emerging Pathological Entity And Its Clinical Implications, Takeshi Tsuda, Gina Patel

Department of Pediatrics Faculty Papers

Coronary microvascular dysfunction (CMD) encompasses a spectrum of structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without obstruction in epicardial coronary artery. The pathogenesis of CMD is complex involving both functional and structural alteration in the coronary microcirculation. In adults, CMD is predominantly discussed in context with anginal chest pain or existing ischemic heart disease and its risk factors. The presence of CMD suggests increased risk of adverse cardiovascular events independent of coronary atherosclerosis. Coronary microvascular dysfunction is also known in children but is rarely recognized due to paucity of concommitent …


Cavernous Wonders: Delving Into Cavernous Sinus Syndrome In Neuro-Ophthalmology, Anza Rizvi, Ba Apr 2024

Cavernous Wonders: Delving Into Cavernous Sinus Syndrome In Neuro-Ophthalmology, Anza Rizvi, Ba

inSIGHT

Cavernous sinus syndrome (CSS) is any disease process that affects the cavernous sinus. This syndrome is marked by a complex interplay of neurovascular symptoms, primarily due to the compression or dysfunction of the cranial nerves that traverse the cavernous sinus. Understanding the intricate details of this syndrome is critical to providing optimal care and improving patient outcomes.


Seeing Clearly: A Bright Future With Light Adjustable Intraocular Lenses For Presbyopia, Shady Mina, Bs Apr 2024

Seeing Clearly: A Bright Future With Light Adjustable Intraocular Lenses For Presbyopia, Shady Mina, Bs

inSIGHT

Presbyopia, or the age-related decline in the ability to focus on near objects, is a common vision disorder that affects 1.8 billion people globally, with this number expected to increase to 2.1 billion by 2030.1-4 A diminished accommodation response is the primary cause of presbyopia.1 The eye has a very complex accommodation mechanism that permits people to distinctly see objects from various distances.1,3 Even though the precise mechanism of accommodation is yet to be determined, the current evidence strongly supports Helmholtz’s theory, which claims that the thickness and curvature of the eye’s lens increase while its diameter …


Medical Missions, Ethical Considerations And The Future For Healthcare Delivery In Ophthalmology, Robert Medina, Ba Apr 2024

Medical Missions, Ethical Considerations And The Future For Healthcare Delivery In Ophthalmology, Robert Medina, Ba

inSIGHT

Beginning hundreds of years ago, priests from Europe embarked on ‘medical missions’ with the goals of delivering care to the body, mind, and soul. Hundreds of years later, members of the United States healthcare system set out on humanitarian medical missions to provide medical assistance to communities in developing countries.1 The concept of providing care internationally as a product of global social responsibility has become engrained in the United States healthcare system, and is popular among providers, trainees, and pre-medical students. In 2023, 21.8% (n = 3264) of matriculating medical students reported participating in international volunteer work, while 7.0% …


Chronic Progressive External Ophthalmoplegia, Bahram Pashaee, Mph, Bs Apr 2024

Chronic Progressive External Ophthalmoplegia, Bahram Pashaee, Mph, Bs

inSIGHT

Chronic progressive external ophthalmoplegia is an inherited or sporadic form of dystrophy that preferentially affects the extraocular muscles of the eye. While this dystrophy can manifest systemically, the extraocular muscles are commonly involved due to their constant metabolic demands and vulnerability to oxidative stress.1 This preferential involvement of the eyelid levator muscle and extraocular muscles makes CPEO an important condition to consider in a differential diagnosis for eyelid asymmetry and double vision among other conditions such as myasthenia gravis, thyroid-associated ophthalmoplegia, and other mitochondrial myopathies.2 This dystrophy tends to occur in the third or fourth decade of life. …


Macular Holes: Diagnosis, Treatment, And Complications, Ayra Khan, Bs Apr 2024

Macular Holes: Diagnosis, Treatment, And Complications, Ayra Khan, Bs

inSIGHT

Macular hole is a condition that affects the central visual field of the eye. Without prompt diagnosis and intervention, macular holes can progressively worsen, significantly impacting both vision and overall quality of life.


Cmv Retinitis: An Expert’S Perspective, Caitlyn Kwun, Ba Apr 2024

Cmv Retinitis: An Expert’S Perspective, Caitlyn Kwun, Ba

inSIGHT

Uveitis is a rare inflammatory disease with a prevalence of around 38 per 100,000 people and is the overall 5th leading cause of blindness in the developed world.1,2 Uveitis is most commonly found in patients younger than 40 years of age, but it can occur in any age group with an etiology that varies within each age demographic.1,3 While the etiology of certain forms of uveitis are not fully understood, there are some that are autoimmune in nature and others that are associated with systemic diseases such as sarcoidosis.4 Uveitis may be inflammatory or infectious. It may …


Bridging The Global Gap Of Blindness Through Artificial Intelligence - Exploring The Tools Of Ai To Address The Top Causes Of Blindness In Under-Resourced Communities Worldwide, Nathan Delacth, Bs Apr 2024

Bridging The Global Gap Of Blindness Through Artificial Intelligence - Exploring The Tools Of Ai To Address The Top Causes Of Blindness In Under-Resourced Communities Worldwide, Nathan Delacth, Bs

inSIGHT

Technological advancements have allowed us to submerge in a sea of innovation and excellence in medicine. Electronic health records transformed the healthcare landscape, improving portability of patient information while streamlining communication and fostering collaboration.1 Imaging technologies, such as magnetic resonance imaging (MRI) and Optical computed tomography (OCT), granted us the ability to view internal structures using non-invasive methods. In a similar vein, artificial intelligence (AI) has emerged as an impactful force in various fields of medicine, and its influence on ophthalmology is no exception.


Evolution Of Lamellar Keratoplasty, Ishan Kasat, Bs Apr 2024

Evolution Of Lamellar Keratoplasty, Ishan Kasat, Bs

inSIGHT

Overview of Keratoplasty The evolution of corneal transplantation, or keratoplasty, has seen a paradigm shift from traditional penetrating keratoplasty (PKP) to the refined precision of lamellar keratoplasty (LK). Penetrating, or full thickness, keratoplasty is a replacement of all corneal layers: epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium.1 Lamellar, or partial thickness, keratoplasty involves replacement of either epithelium and stroma (anterior lamellar) or Descemet’s membrane and endothelium (posterior lamellar).2 From 1985 to 2004, over 95% of graft tissues were used for PKP. However, from 2005 to 2014, the percentage of PKP procedures decreased from 95% to 42%, while …


The Myopia Epidemic: Exploring The Pathology And Management Of The World’S Most Common Eye Disorder, Gabriella Baldassarre, Bs Apr 2024

The Myopia Epidemic: Exploring The Pathology And Management Of The World’S Most Common Eye Disorder, Gabriella Baldassarre, Bs

inSIGHT

Myopia is the most common eye disorder in the world and an increasing cause of vision impairment in children.1 Myopia is an imbalance in the refractive components of the eye and its length, leading to inaccurate focusing of light rays in front of the retina tissue instead of on it. There is a spectrum of severity of myopia, from mild nearsightedness to a more severe form known as high or degenerative myopia, which has the potential to cause vision loss and blindness. There is evidence of a developing myopia epidemic, with an estimated one-third of the world population affected …


Insight, Volume 4, Issue 1, 2024 Apr 2024

Insight, Volume 4, Issue 1, 2024

inSIGHT

Contents

8 - The Myopia Epidemic: Exploring the Pathology and Management of the World’s Most Common Eye Disorder
By Gabriella Baldassare

15 - Evolution of Lamellar Keratoplasty
By Ishan Kasat

19 - Bridging the Global Gap of Blindness Through Artificial Intelligence
By Nathan Delacth

24 - CMV Retinitis: An Expert’s Perspective
By Caitlyn Kwun

29 - Macular Holes: Diagnosis, Treatment, and Complications
By Ayra Khan

36 - Chronic Progressive External Ophthalmoplegia
By Bahram Pashaee

39 - Medical Missions, Ethical Considerations, and the Future for Healthcare Delivery in Ophthalmology
By Robert Medina

43 - Shaping the Future of Vision: The Rise …


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.


Application Of Quality And Patient Safety Principles To Improve Patient Mobility, Sandhyadevi Tagaram, Md Apr 2024

Application Of Quality And Patient Safety Principles To Improve Patient Mobility, Sandhyadevi Tagaram, Md

Master of Science in Healthcare Quality and Safety Capstone Presentations

Decreased patient mobility in hospitals leads to an increased incidence of hospital-associated complications, falls, and delirium, resulting in prolonged post-hospital stays, an increase in patient mortality, morbidity, and rise in healthcare costs and utilization. Our project, UMove to IMPROVE, was piloted in two medical-surgical units in November 2023 to enhance safe patient mobility practices, improve patient flow and reduce hospital-associated complications.

The nursing and PCAs will assess the patient's baseline mobility and their level of assistance at admission and during the shift changes by calculating the activity measure for post-acute care( AMPAC) score. The AMPAC scores are used to assess …


Differential Susceptibility To Propofol And Ketamine In Primary Cultures Of Young And Senesced Astrocytes, Liang Huang, Ferit Tuzer, Abigail Murtha, Michael Green, Claudio Torres, Henry Liu, Shadi Malaeb Apr 2024

Differential Susceptibility To Propofol And Ketamine In Primary Cultures Of Young And Senesced Astrocytes, Liang Huang, Ferit Tuzer, Abigail Murtha, Michael Green, Claudio Torres, Henry Liu, Shadi Malaeb

Department of Anesthesiology Faculty Papers

The adverse effects of general anesthesia on the long-term cognition of young children and senior adults have become of concern in recent years. Previously, mechanistic and pathogenic investigations focused on neurons, and little is known about the effect of commonly used intravenous anesthetics such as propofol and ketamine on astrocytes. Recently, astrocyte dysfunction has been implicated in a wide range of age-related brain diseases. In this study, we examined the survival and viability of both young and senescent astrocytes in culture after adding propofol and ketamine to the media at varying strengths. Oxidative stimulus was applied to commercially available fetal …


Case Report: Low-Risk Hpv Associated Verruco-Papillary Squamous Cell Carcinoma Of The Cervix, Olivia Nicolais, Mackenzie Cummings, Tommy R. Buchanan Apr 2024

Case Report: Low-Risk Hpv Associated Verruco-Papillary Squamous Cell Carcinoma Of The Cervix, Olivia Nicolais, Mackenzie Cummings, Tommy R. Buchanan

Abington Jefferson Health Papers

•Cervical cancer plays a large role in morbidity and mortality for gynecologic cancer.•Most cases are involved with high-risk HPV, rare cases of low-risk HPV associated cancer exists.•Low risk HPV associated cervical cancers have increased difficulty in diagnosis.•No distinction exists in treatment between low and high risk HPV associated cervical cancer.


Altered Platelet-Megakaryocyte Endocytosis And Trafficking Of Albumin And Fibrinogen In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Guangfen Mao, Lawrence E. Goldfinger, Jeremy Wurtzel, Liying Guan, Mohammad Afaque Alam, Kiwon Lee, Mortimer Poncz, A. Koneti Rao Apr 2024

Altered Platelet-Megakaryocyte Endocytosis And Trafficking Of Albumin And Fibrinogen In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Guangfen Mao, Lawrence E. Goldfinger, Jeremy Wurtzel, Liying Guan, Mohammad Afaque Alam, Kiwon Lee, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

Platelet α-granules have numerous proteins, some synthesized by megakaryocytes (MK) and others not synthesized but incorporated by endocytosis, an incompletely understood process in platelets/MK. Germ line RUNX1 haplodeficiency, referred to as familial platelet defect with predisposition to myeloid malignancies (FPDMMs), is associated with thrombocytopenia, platelet dysfunction, and granule deficiencies. In previous studies, we found that platelet albumin, fibrinogen, and immunoglobulin G (IgG) were decreased in a patient with FPDMM. We now show that platelet endocytosis of fluorescent-labeled albumin, fibrinogen, and IgG is decreased in the patient and his daughter with FPDMM. In megakaryocytic human erythroleukemia (HEL) cells, small interfering RNA …


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 …


Primary Anastomosis With Diverting Loop Ileostomy Vs. Hartmann's Procedure For Acute Diverticulitis: What Happens After Discharge? Results Of A Nationwide Analysis, Arturo J. Rios Diaz, Lisa A. Bevilacqua, Theodore E. Habarth-Morales, Alicja Zalewski, David Metcalfe, Caitlyn Costanzo, Charles J. Yeo, Francesco Palazzo Apr 2024

Primary Anastomosis With Diverting Loop Ileostomy Vs. Hartmann's Procedure For Acute Diverticulitis: What Happens After Discharge? Results Of A Nationwide Analysis, Arturo J. Rios Diaz, Lisa A. Bevilacqua, Theodore E. Habarth-Morales, Alicja Zalewski, David Metcalfe, Caitlyn Costanzo, Charles J. Yeo, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: Current guidelines recommend resection with primary anastomosis with diverting loop ileostomy over Hartmann's procedure if deemed safe for acute diverticulitis. The primary objective of the current study was to compare the utilization of these strategies and describe nationwide ostomy closure patterns and readmission outcomes within 1 year of discharge.

METHODS: This was a retrospective, population-based, cohort study of United States Hospitals reporting to the Nationwide Readmissions Database from January 2011 to December 2019. There were 35,774 patients identified undergoing non-elective primary anastomosis with diverting loop ileostomy or Hartmann's procedure for acute diverticulitis. Rates of ostomy closure, unplanned readmissions, and …


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.


Idiopathic Intracranial Hypertension After Abrupt Cessation Of Medication: A Case Report Of Abrupt Glucagon-Like Peptide-1 (Glp-1) Receptor Agonist Cessation And Review Of The Literature, Brittany Heckel Apr 2024

Idiopathic Intracranial Hypertension After Abrupt Cessation Of Medication: A Case Report Of Abrupt Glucagon-Like Peptide-1 (Glp-1) Receptor Agonist Cessation And Review Of The Literature, Brittany Heckel

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: The purpose of this review is two-fold: (1) to discuss a case report of idiopathic intracranial hypertension (IIH) after abrupt cessation of a glucagon-like peptide-1 (GLP-1) receptor agonist with resultant rapid weight gain and (2) to review the literature regarding the potential role of GLP-1 receptor agonists in the treatment of IIH as well as potential pitfalls.

RECENT FINDINGS: GLP-1 receptor agonists have become widely used to treat obesity. Obesity is a known risk factor for the development of IIH, though the precise pathophysiology is unclear. GLP-1 receptor agonists may help treat IIH by promoting weight loss, …


The Clinical Implications Of Kras Mutations And Variant Allele Frequencies In Pancreatic Ductal Adenocarcinoma, Faria Nusrat, Akshay Khanna, Aditi Jain, Wei Jiang, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler Apr 2024

The Clinical Implications Of Kras Mutations And Variant Allele Frequencies In Pancreatic Ductal Adenocarcinoma, Faria Nusrat, Akshay Khanna, Aditi Jain, Wei Jiang, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler

Department of Surgery Faculty Papers

The KRAS proto-oncogene is a major driver of pancreatic tumorigenesis and is nearly ubiquitously mutated in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are detected in over 90% of PDAC cases, and these mutations have been shown to be associated with worse therapy response and overall survival. Pathogenic KRAS mutations are mostly limited to codons 12, 13 and 61, with G12D, G12V, G12R, Q61H, and G13D accounting for approximately 95% of the mutant cases. Emerging data have shown the importance of specific mutant subtypes, as well as KRAS variant allele frequency on clinical prognosis. Furthermore, novel technologies and therapies are …