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Articles 69781 - 69810 of 325197

Full-Text Articles in Medicine and Health Sciences

Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al. Nov 2023

Dominant Negative Variants In Kif5b Cause Osteogenesis Imperfecta Via Down Regulation Of Mtor Signaling, Ronit Marom, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, Stephen C. Pak, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown.

METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, …


Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan Nov 2023

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

2020-Current year OA Pubs

BACKGROUND: Invasive infections caused by

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution.

RESULTS: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In …


Targeted Proteomic Quantitation Of Nrf2 Signaling And Predictive Biomarkers In Hnscc, Nathan T Wamsley, Emily M Wilkerson, Kyle M Lapak, Robert W Sprung, Petra Erdmann Gilmore, Sophie P Gerndt, Ryan S Jackson, Randal C Paniello, Patrik Pipkorn, Sidharth V Puram, Jason T Rich, Reid R Townsend, José P Zevallos, Paul Zolkind, Dennis Goldfarb, Michael B Major, Et Al. Nov 2023

Targeted Proteomic Quantitation Of Nrf2 Signaling And Predictive Biomarkers In Hnscc, Nathan T Wamsley, Emily M Wilkerson, Kyle M Lapak, Robert W Sprung, Petra Erdmann Gilmore, Sophie P Gerndt, Ryan S Jackson, Randal C Paniello, Patrik Pipkorn, Sidharth V Puram, Jason T Rich, Reid R Townsend, José P Zevallos, Paul Zolkind, Dennis Goldfarb, Michael B Major, Et Al.

2020-Current year OA Pubs

The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on …


Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al. Nov 2023

Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.

2020-Current year OA Pubs

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2

DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.

RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …


A Not-So-Sweet Syndrome: A Case Report Of A Male Presenting With Acute Febrile Neutrophilic Dermatosis, Kim-Long R. Nguyen, Aaron J. Lacy, Suelin Hilbert, Rosanne S. Naunheim Nov 2023

A Not-So-Sweet Syndrome: A Case Report Of A Male Presenting With Acute Febrile Neutrophilic Dermatosis, Kim-Long R. Nguyen, Aaron J. Lacy, Suelin Hilbert, Rosanne S. Naunheim

2020-Current year OA Pubs

Physicians often encounter patients who present with a chief complaint of skin changes or lesions in both acute and primary care settings. Early initiation of appropriate treatment and pharmacotherapy in patients who present with rash is crucial to prevent decompensation, morbidity, and further downstream utilization of hospital resources. Acute febrile neutrophilic dermatosis, more commonly known as Sweet syndrome, is a rare and highly symptomatic inflammatory skin condition. Early recognition of Sweet syndrome is important as it requires specific treatment considerations and often can be a sign of an underlying pro-inflammatory condition, malignancy, or reaction to new medication that must be …


Advances In Screening For Radiation-Associated Cardiotoxicity In Cancer Patients, Walter Schiffer, Lauren N Pedersen, Matthew Lui, Carmen Bergom, Joshua D Mitchell Nov 2023

Advances In Screening For Radiation-Associated Cardiotoxicity In Cancer Patients, Walter Schiffer, Lauren N Pedersen, Matthew Lui, Carmen Bergom, Joshua D Mitchell

2020-Current year OA Pubs

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects.

RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, …


Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz Nov 2023

Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz

2020-Current year OA Pubs

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk.

METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the …


A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn Nov 2023

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

2020-Current year OA Pubs

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …


Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al. Nov 2023

Duvelisib For Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial, Scott R Goldsmith, Fahrettin Covut, Mark Fiala, Zhifu Xiang, Zahid Iqbal, Elizabeth Bradtke, Brandon Christen, Michael P Rettig, Stephanie Christ, Leah Gehrs, Emily Street, Nicholas Wallace, Julie Ritchey, Feng Gao, Bijal Parikh, Erik R Dubberke, John F Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness.

METHODS: We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants …


Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Walter Bosch, Et Al. Nov 2023

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …


Overcoming Barriers To Drug Development And Enrollment In Clinical Trials For Adolescents And Young Adults With Lymphoma, Keri Toner, Carl E Allen, Shweta Jain, Brad Kahl, John Leonard, Heather Wasserstrom, Jonathan W Friedberg, Nita L Seibel, Kara Kelly Nov 2023

Overcoming Barriers To Drug Development And Enrollment In Clinical Trials For Adolescents And Young Adults With Lymphoma, Keri Toner, Carl E Allen, Shweta Jain, Brad Kahl, John Leonard, Heather Wasserstrom, Jonathan W Friedberg, Nita L Seibel, Kara Kelly

2020-Current year OA Pubs

Lymphoma is one of the most common cancers in adolescents and young adults, but historically, this population has had lower clinical trial enrollment and improvements in overall survival as compared to other age populations. There are multiple challenges that are unique to this population that have affected drug development and clinical trial enrollment. Our panel of experts have identified barriers, and in this review, we discuss current methods to address these barriers as well as potential solutions moving forward.


Type 2 Immunity In The Brain And Brain Borders, Tornike Mamuladze, Jonathan Kipnis Nov 2023

Type 2 Immunity In The Brain And Brain Borders, Tornike Mamuladze, Jonathan Kipnis

2020-Current year OA Pubs

Recent research in neuroimmunology has revolutionized our understanding of the intricate interactions between the immune system and the central nervous system (CNS). The CNS, an "immune-privileged organ", is now known to be intimately connected to the immune system through different cell types and cytokines. While type 2 immune responses have traditionally been associated with allergy and parasitic infections, emerging evidence suggests that these responses also play a crucial role in CNS homeostasis and disease pathogenesis. Type 2 immunity encompasses a delicate interplay among stroma, Th2 cells, innate lymphoid type 2 cells (ILC2s), mast cells, basophils, and the cytokines interleukin (IL)-4, …


Current Directions In The Treatment Of Classical Hodgkin Lymphoma, Frank G Keller, Brad Kahl, Jonathan W Friedberg Nov 2023

Current Directions In The Treatment Of Classical Hodgkin Lymphoma, Frank G Keller, Brad Kahl, Jonathan W Friedberg

2020-Current year OA Pubs

Optimal management of patients who present with Hodgkin lymphoma continues to evolve. Most patients are cured with current treatment strategies, some but both short and long-term morbidity and mortality from treatment have particular relevance given the youth of the patient population. Combininations of targeted agents together with conventional chemotherapy have recently been investigated in phase 3 cliniial trials for advanced-stage Hodkgkin lymphoma, and have demonstrated improved efficacy compared with chemotherapy alone. These include both antibody-drug conjugates and PD-1 blockade. Treatment approaches have historically differed between pediatric and adult groups, but recent collaborations between adullt and pediatric groups via the NCTN …


Six-Month Outcomes Of Mechanical Thrombectomy For Treating Deep Vein Thrombosis: Analysis From The 500-Patient Clout Registry, Abdullah Shaikh, Vipul Khetarpaul, Et Al. Nov 2023

Six-Month Outcomes Of Mechanical Thrombectomy For Treating Deep Vein Thrombosis: Analysis From The 500-Patient Clout Registry, Abdullah Shaikh, Vipul Khetarpaul, Et Al.

2020-Current year OA Pubs

PURPOSE: Mechanical thrombectomy for the treatment of deep vein thrombosis (DVT) is being increasingly utilized to reduce symptoms and prevent postthrombotic syndrome (PTS), but more data on clinical outcomes are needed. Mechanical thrombectomy was studied in the ClotTriever Outcomes (CLOUT) registry with 6-month full analysis outcomes reported herein.

MATERIALS AND METHODS: The CLOUT registry is a prospective, all-comer study that enrolled 500 lower extremity DVT patients across 43 US sites treated with mechanical thrombectomy using the ClotTriever System. Core-lab assessed Marder scores and physician-assessed venous patency by duplex ultrasound, PTS assessment using Villalta score, venous symptom severity, pain, and quality …


Assessing Cancer Risk In The Anterior Part Of The Prostate Using Micro-Ultrasound: Validation Of A Novel Distinct Protocol, Sandy Schaer, Arnas Rakauskas, Julien Dagher, Stefano La Rosa, Jake Pensa, Wayne Brisbane, Leonard Marks, Adam Kinnaird, Robert Abouassaly, Eric Klein, Lewis Thomas, Jean-Yves Meuwly, Pamela Parker, Beat Roth, Massimo Valerio Nov 2023

Assessing Cancer Risk In The Anterior Part Of The Prostate Using Micro-Ultrasound: Validation Of A Novel Distinct Protocol, Sandy Schaer, Arnas Rakauskas, Julien Dagher, Stefano La Rosa, Jake Pensa, Wayne Brisbane, Leonard Marks, Adam Kinnaird, Robert Abouassaly, Eric Klein, Lewis Thomas, Jean-Yves Meuwly, Pamela Parker, Beat Roth, Massimo Valerio

2020-Current year OA Pubs

PURPOSE: To develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone.

METHODS: Patients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the …


Perineal Hernia As A Sequela Of Anal Reconstruction Surgeries In Perianal Crohn's Disease, Favour O Garuba, Josh M Mcphie, Rachel A Anolik, Parakkal Deepak, David H Ballard, Radhika K Smith Nov 2023

Perineal Hernia As A Sequela Of Anal Reconstruction Surgeries In Perianal Crohn's Disease, Favour O Garuba, Josh M Mcphie, Rachel A Anolik, Parakkal Deepak, David H Ballard, Radhika K Smith

2020-Current year OA Pubs

Perineal hernia is a rare complication of pelvic surgeries that can occur in patients with perianal Crohn's disease (pCD) as a long-term outcome of surgeries for complex fistula treatment. We present a case of a symptomatic pCD male patient with multiple perianal surgeries who presents with anal pain, diarrhea, and discharge. Magnetic resonance imaging showed a perineal hernia in the ischioanal fossa violating the convergence of the left external sphincter complex. The hernia was treated with an open primary hernia repair via the perineal approach. It recurred after 3 months, and the patient underwent secondary hernia repair with gracilis muscle …


Parenchymal Border Macrophages Regulate Tau Pathology And Tau-Mediated Neurodegeneration, Antoine Drieu, Siling Du, Michal Kipnis, Megan E Bosch, Jasmin Herz, Choonghee Lee, Hong Jiang, Melissa Manis, Jason D Ulrich, Jonathan Kipnis, David M Holtzman, Maud Gratuze Nov 2023

Parenchymal Border Macrophages Regulate Tau Pathology And Tau-Mediated Neurodegeneration, Antoine Drieu, Siling Du, Michal Kipnis, Megan E Bosch, Jasmin Herz, Choonghee Lee, Hong Jiang, Melissa Manis, Jason D Ulrich, Jonathan Kipnis, David M Holtzman, Maud Gratuze

2020-Current year OA Pubs

Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer's disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII


The Association Between Reasons For First Using Cannabis, Later Pattern Of Use, And Risk Of First-Episode Psychosis: The Eu-Gei Case-Control Study, Edoardo Spinazzola, Emma C Johnson, Et Al. Nov 2023

The Association Between Reasons For First Using Cannabis, Later Pattern Of Use, And Risk Of First-Episode Psychosis: The Eu-Gei Case-Control Study, Edoardo Spinazzola, Emma C Johnson, Et Al.

2020-Current year OA Pubs

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status.

RESULTS: Controls (86.1%) …


Deactivation Of Left Ventricular Assist Devices At The End Of Life: Narrative Review And Ethical Framework, Danish Zaidi, James N Kirkpatrick, Savitri E Fedson, Sarah C Hull Nov 2023

Deactivation Of Left Ventricular Assist Devices At The End Of Life: Narrative Review And Ethical Framework, Danish Zaidi, James N Kirkpatrick, Savitri E Fedson, Sarah C Hull

Center for Medical Ethics and Health Policy Staff Publications

Left ventricular assist devices (LVADs) have become an increasingly common advanced therapy in patients with severe symptomatic heart failure. Their unique nature in prolonging life through incorporation into the circulatory system raises ethical questions regarding patient identity and values, device ontology, and treatment categorization; approaching requests for LVAD deactivation requires consideration of these factors, among others. To that end, clinicians would benefit from a deeper understanding of: 1) the history and nature of LVADs; 2) the wider context of device deactivation and associated ethical considerations; and 3) an introductory framework incorporating best practices in requests for LVAD deactivation (specifically in …


Obstetrics And Gynecology Clerkship Directors' Experiences Advising Residency Applicants, Helen K Morgan, Laura Baecher-Lind, Rashmi Bhargava, Susan Cox, Elise Everett, Angela Fleming, Scott Graziano, Chris Morosky, Celeste Royce, Tammy Sonn, Jill Sutton, Shireen Madani Sims Nov 2023

Obstetrics And Gynecology Clerkship Directors' Experiences Advising Residency Applicants, Helen K Morgan, Laura Baecher-Lind, Rashmi Bhargava, Susan Cox, Elise Everett, Angela Fleming, Scott Graziano, Chris Morosky, Celeste Royce, Tammy Sonn, Jill Sutton, Shireen Madani Sims

2020-Current year OA Pubs

BACKGROUND: The evolving landscape of application processes for obstetrics and gynecology residency applicants poses many challenges for applicants and advisors. The lack of data coordination among national groups creates crucial gaps in information for stakeholder groups.

OBJECTIVE: This study aimed to identify the current state of the advising milieu for obstetrics and gynecology residency applicants and their career advisors, the annual Association of Professors of Gynecology and Obstetrics survey focused on US clerkship directors' experiences advising students through these processes.

STUDY DESIGN: A 23-item anonymous survey was developed that asked respondents about demographics and outcomes for the students that they …


Protein Kinase Signaling Networks Driven By Oncogenic Gq/11 In Uveal Melanoma Identified By Phosphoproteomic And Bioinformatic Analyses, Michael D Onken, Petra Erdmann-Gilmore, Qiang Zhang, Kisan Thapa, Emily King, Kevin M Kaltenbronn, Sarah E Noda, Carol M Makepeace, Dennis Goldfarb, Özgün Babur, R Reid Townsend, Kendall J Blumer Nov 2023

Protein Kinase Signaling Networks Driven By Oncogenic Gq/11 In Uveal Melanoma Identified By Phosphoproteomic And Bioinformatic Analyses, Michael D Onken, Petra Erdmann-Gilmore, Qiang Zhang, Kisan Thapa, Emily King, Kevin M Kaltenbronn, Sarah E Noda, Carol M Makepeace, Dennis Goldfarb, Özgün Babur, R Reid Townsend, Kendall J Blumer

2020-Current year OA Pubs

Metastatic uveal melanoma (UM) patients typically survive only 2 to 3 years because effective therapy does not yet exist. Here, to facilitate the discovery of therapeutic targets in UM, we have identified protein kinase signaling mechanisms elicited by the drivers in 90% of UM tumors: mutant constitutively active G protein α-subunits encoded by GNAQ (Gq) or GNA11 (G11). We used the highly specific Gq/11 inhibitor FR900359 (FR) to elucidate signaling networks that drive proliferation, metabolic reprogramming, and dedifferentiation of UM cells. We determined the effects of FR on the proteome and phosphoproteome of UM cells as indicated by bioinformatic analyses …


Health-Related Quality-Of-Life In Treatment-Naive Cll/Sll Patients Treated With Zanubrutinib Versus Bendamustine Plus Rituximab, Paolo Ghia, Gisoo Barnes, Keri Yang, Constantine S Tam, Tadeusz Robak, Jennifer R Brown, Brad S Kahl, Tian Tian, Andy Szeto, Jason C Paik, Mazyar Shadman Nov 2023

Health-Related Quality-Of-Life In Treatment-Naive Cll/Sll Patients Treated With Zanubrutinib Versus Bendamustine Plus Rituximab, Paolo Ghia, Gisoo Barnes, Keri Yang, Constantine S Tam, Tadeusz Robak, Jennifer R Brown, Brad S Kahl, Tian Tian, Andy Szeto, Jason C Paik, Mazyar Shadman

2020-Current year OA Pubs

OBJECTIVE: Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality-of-life (HRQoL).

METHODS: In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires' scales and a mixed …


Newer Insights Into Mmtv Replication: The Human Retroviral Proteins Hiv-1 Tat And Htlv-1 Tax Can Transactivate The Mmtv Novel 5’ Element, Thanumol Abdul Khader Nov 2023

Newer Insights Into Mmtv Replication: The Human Retroviral Proteins Hiv-1 Tat And Htlv-1 Tax Can Transactivate The Mmtv Novel 5’ Element, Thanumol Abdul Khader

Dissertations

The mouse mammary tumor virus (MMTV) is a prototypic betaretrovirus that causes breast cancer in mice. MMTV regulates its gene expression both at the transcriptional and post transcriptional levels. It has hormonally-regulated promoters controlled by negative regulatory factors in a tissue-specific manner. Recently, we identified a novel 24-nucleotide region at the 5' end of the MMTV genome crucial for MMTV gene expression. Its deletion resulted in disruption of MMTV transcript elongation and stability, leading to a complete loss of Gag gene expression. This conserved element is present within the bifurcated stem loop 4, responsible for gRNA dimerization and encapsidation, into …


Quad Bike Injuries In The United Arab Emirates: Evidence For Injury Prevention Strategies, Preetha Menon Karuveetil Nov 2023

Quad Bike Injuries In The United Arab Emirates: Evidence For Injury Prevention Strategies, Preetha Menon Karuveetil

Dissertations

Quad bikes, also known as All-Terrain Vehicles (ATVs), are versatile vehicles designed for navigating uneven terrain. Originally intended for agricultural purposes, they have gained popularity for recreational use, particularly in the middle east, notably the United Arab Emirates (UAE). While these vehicles offer health benefits, they are associated with substantial safety risks, resulting in injuries ranging from lacerations to severe traumatic injuries, imposing a significant economic burden on healthcare systems.

This research addresses a critical gap in the existing literature by focusing on quad bike injuries in the unique context of the UAE, taking into account its desert environment, rider …


Effects Of Adropin On Metabolic Parameters, Oxidative Stress, And Cell Proliferation In Animal Model Of Diabetes Mellitus, Ifrah Ismail Ali Nov 2023

Effects Of Adropin On Metabolic Parameters, Oxidative Stress, And Cell Proliferation In Animal Model Of Diabetes Mellitus, Ifrah Ismail Ali

Dissertations

Diabetes Mellitus (DM) is a major health condition that has reached alarming levels, affecting around 537 million of the global adult population. DM is a group of metabolic diseases characterized by hyperglycemia with disturbance in carbohydrate, fat, and protein metabolism. The proposed therapeutic options for DM are different according to their mechanism of action, and peptide therapy is one of these options. Adropin, a peptide hormone involved in energy homeostasis, has shown promising results in the treatment of diabetes by lowering fasting blood glucose, reducing insulin resistance, and minimizing fat storage. Moreover, it has been demonstrated that adropin is engaged …


Trauma-Informed Youth Sport: Identifying Program Characteristics And Challenges To Advance Practice, Kayla Hussey, Lindsey C. Blom, Zenzi Huysmans, Dana Voelker, Matt Moore, Thalia M. Mulvihill Nov 2023

Trauma-Informed Youth Sport: Identifying Program Characteristics And Challenges To Advance Practice, Kayla Hussey, Lindsey C. Blom, Zenzi Huysmans, Dana Voelker, Matt Moore, Thalia M. Mulvihill

Journal of Youth Development

This purpose of this qualitative study was to explore shared characteristics and local challenges of trauma-informed youth sport program design and implementation through the voices of ten program facilitators (e.g., director, trainer; 8 women, 2 men; average age of 36.2 years, SD = 6.03) across four U.S. regions. Within a postpositivist approach and through thematic analysis of semi-structured interviews (average length of 53 minutes), shared characteristics identified by facilitators included promoting a safe and supportive environment, cultivating healthy relationships among adults and peers, and intentional psychological and social skill-building (e.g., attentional cues). Facilitators also explained the importance of understanding the …


Subungual Squamous Cell Carcinoma Leading To Arm Amputation, Ovidiu V. Fabian, Emilia Maria Pătruţ, Mădălina Șteţca, Radu Mircea Galasiu, Vlad Zolog, Adriana Zolog, Iacob Domşa, Ioan Șimon, Anca Mihailov, Olga Hilda Orăşan, Flaviu Mureşan Oct 2023

Subungual Squamous Cell Carcinoma Leading To Arm Amputation, Ovidiu V. Fabian, Emilia Maria Pătruţ, Mădălina Șteţca, Radu Mircea Galasiu, Vlad Zolog, Adriana Zolog, Iacob Domşa, Ioan Șimon, Anca Mihailov, Olga Hilda Orăşan, Flaviu Mureşan

Journal of Mind and Medical Sciences

Although rare, subungual carcinoma is the most common malignant nail tumor. The symptomatology is not characteristic, being very similar to that of other nail and periungual diseases. For this reason, early diagnosis is usually established by performing a biopsy. With appropriate treatment, subungual carcinoma usually has a favorable prognosis. Metastatic cases are rarely encountered, but they usually have a poor therapeutic result. This article presents the case of a patient with subungual carcinoma (diagnosed by histopathological exam), initially treated by amputation of the distal and middle phalanges of the fourth finger. Two years after the operation, a recurrence in the …


Giant Renal Cell Carcinoma In A Patient With Ipsilateral Lower Limb Hypertrophic Lichen Planus; Case Report And Literature Review, Silvia Popescu, Dumitru Peța, Zoltan Janos Kövér, Dumitru Toma, Ioan-Teodor Cristea, Mihaela Anca Popescu, Oana-Denisa Bălălău, Romina-Marina Sima, Gabriel-Petre Gorecki, Călin Giurcăneanu Oct 2023

Giant Renal Cell Carcinoma In A Patient With Ipsilateral Lower Limb Hypertrophic Lichen Planus; Case Report And Literature Review, Silvia Popescu, Dumitru Peța, Zoltan Janos Kövér, Dumitru Toma, Ioan-Teodor Cristea, Mihaela Anca Popescu, Oana-Denisa Bălălău, Romina-Marina Sima, Gabriel-Petre Gorecki, Călin Giurcăneanu

Journal of Mind and Medical Sciences

Renal cell carcinoma is the most common type of primary urogenital cancer, usually resistant to radiotherapy and chemotherapy. Hypertrophic lichen planus is an inflammatory dermatosis characterized by the presence of papulosquamous and intensely pruritic lesions. The association of these two conditions is unusual, being reported in the specialized literature only in a few rare cases with the onset of lichenoid lesions after patients have undergone various forms of treatment. The case of a 62-year-old male patient who was admitted for severe abdominal pain due to a giant renal tumor associated with a hypertrophic plaque located on the anterior part of …


Periodontal Status And Inflammatory Markers In Gingival Crevicular Fluid Of Patients With Periodontitis And Colorectal Cancer, Sandu Râmboiu, Flavia Mirela Nicolae, Andrada Soancă, Dorin Nicolae Gheorghe, Dora Maria Popescu, Bogdan Silviu Ungureanu, Dragoș Nicolae Mărgăritescu, Adina Turcu-Știolica, Mihail Virgil Boldeanu, Valeriu Marin Șurlin, Dan Ionuț Gheonea, Petra Șurlin Oct 2023

Periodontal Status And Inflammatory Markers In Gingival Crevicular Fluid Of Patients With Periodontitis And Colorectal Cancer, Sandu Râmboiu, Flavia Mirela Nicolae, Andrada Soancă, Dorin Nicolae Gheorghe, Dora Maria Popescu, Bogdan Silviu Ungureanu, Dragoș Nicolae Mărgăritescu, Adina Turcu-Știolica, Mihail Virgil Boldeanu, Valeriu Marin Șurlin, Dan Ionuț Gheonea, Petra Șurlin

Journal of Mind and Medical Sciences

Objectives. The present pilot study was carried out to evaluate the periodontal status, the levels of interleukin-6 and tumor necrosis factor alpha in gingival crevicular fluid on hospitalized patients with colorectal cancer. Materials and Methods. The sample of our study was represented by 74 patients with colorectal cancer. They were assigned to one of the two study groups, based on cancer’s stages, as follows: (i) stage III-IV: 51 patients (A-group); (ii) stage I-II: 23 patients (B-group). For each participant periodontal parameters were recorded and gingival crevicular fluid samples were collected and immunologically assessed. Results. Statistically significant differences were found between …


Is Open Surgery Still Part Of The Current Treatment Of Inguinal Hernias?, Dan Bratu, Alin Mihetiu, Alexandra Sandu, Crenguta Serboiu, Corneliu Tudor, Laurentiu Simion, Dragos Cretoiu, Florin Bobirca, Dragos Davitoiu, Bogdan Serban, Claudiu Eduard Nistor Oct 2023

Is Open Surgery Still Part Of The Current Treatment Of Inguinal Hernias?, Dan Bratu, Alin Mihetiu, Alexandra Sandu, Crenguta Serboiu, Corneliu Tudor, Laurentiu Simion, Dragos Cretoiu, Florin Bobirca, Dragos Davitoiu, Bogdan Serban, Claudiu Eduard Nistor

Journal of Mind and Medical Sciences

Inguinal hernia repair represents one of the most frequent pathologies with surgical addressability. From the multitude of surgical procedures, a limited number still keep their indication in the current treatment of hernias. Open surgery, the exclusive repair method until recently, is associated with laparoscopic techniques with benefits that are at least superposable on those in open repair. We conducted a study, analyzing several types of procedures in open surgery and comparing them to each other, but also with the TAPP approach, which is still at the beginning in our service. The non-mesh procedures scored poorly in terms of recurrence, the …