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Articles 12571 - 12600 of 76901

Full-Text Articles in Medical Specialties

Maturity-Onset Diabetes Of The Young: A Proposal For Updated Nomenclature, Mustafa Tosur Dec 2024

Maturity-Onset Diabetes Of The Young: A Proposal For Updated Nomenclature, Mustafa Tosur

Faculty, Staff and Students Publications

Given the contemporary understanding of diabetes genetics, the term "maturity-onset diabetes of the young (MODY)" warrants renaming. I propose adopting the term "monogenic diabetes" in conjunction with the specific gene name.


Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators Dec 2024

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …


Development And Evaluation Of A Training Curriculum To Engage Researchers On Accessing And Analyzing The All Of Us Data, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Elizabeth G Atkinson, Debra D Murray, Brendan Lee, Kim C Worley Dec 2024

Development And Evaluation Of A Training Curriculum To Engage Researchers On Accessing And Analyzing The All Of Us Data, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Elizabeth G Atkinson, Debra D Murray, Brendan Lee, Kim C Worley

Faculty, Staff and Students Publications

OBJECTIVE: The All of Us Evenings with Genetics (EwG) Research Program at Baylor College of Medicine (BCM), funded to engage research scholars to work with the All of Us data, developed a training curriculum for the Researcher Workbench, the platform to access and analyze All of Us data. All of Us EwG developed the curriculum so that it could teach scholars regardless of their skills and background in programming languages and cloud computing. All of Us EwG delivered this curriculum at the first annual All of Us EwG Faculty Summit in May 2022. The curriculum was evaluated both during and …


A Comprehensive Perspective On Intracranial Pressure Monitoring And Individualized Management In Neurocritical Care: Results Of A Survey With Global Experts, Sérgio Brasil, Daniel Agustín Godoy, Walter Videtta, Andrés Mariano Rubiano, Davi Solla, Fabio Silvio Taccone, Chiara Robba, Frank Rasulo, Marcel Aries, Peter Smielewski, Geert Meyfroidt, Denise Battaglini, Mohammad I Hirzallah, Robson Amorim, Gisele Sampaio, Fabiano Moulin, Cristian Deana, Edoardo Picetti, Angelos Kolias, Peter Hutchinson, Gregory W Hawryluk, Marek Czosnyka, Ronney B Panerai, Lori A Shutter, Soojin Park, Carla Rynkowski, Jorge Paranhos, Thiago H S Silva, Luiz M S Malbouisson, Wellingson S Paiva Dec 2024

A Comprehensive Perspective On Intracranial Pressure Monitoring And Individualized Management In Neurocritical Care: Results Of A Survey With Global Experts, Sérgio Brasil, Daniel Agustín Godoy, Walter Videtta, Andrés Mariano Rubiano, Davi Solla, Fabio Silvio Taccone, Chiara Robba, Frank Rasulo, Marcel Aries, Peter Smielewski, Geert Meyfroidt, Denise Battaglini, Mohammad I Hirzallah, Robson Amorim, Gisele Sampaio, Fabiano Moulin, Cristian Deana, Edoardo Picetti, Angelos Kolias, Peter Hutchinson, Gregory W Hawryluk, Marek Czosnyka, Ronney B Panerai, Lori A Shutter, Soojin Park, Carla Rynkowski, Jorge Paranhos, Thiago H S Silva, Luiz M S Malbouisson, Wellingson S Paiva

Faculty, Staff and Students Publications

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and …


Hands-On Training About Data Clustering With Orange Data Mining Toolbox, Janez Demšar, Blaž Zupan Dec 2024

Hands-On Training About Data Clustering With Orange Data Mining Toolbox, Janez Demšar, Blaž Zupan

Faculty, Staff and Students Publications

Data clustering is a core data science approach widely used and referenced in the scientific literature. Its algorithms are often intuitive and can lead to exciting, insightful results that are easy to interpret. For these reasons, data clustering techniques could be the first method encountered in data science training. This paper proposes a hands-on approach to data clustering training suitable for introductory courses. The education approach features problem-based training that starts with the data and gradually introduces various data processing and analysis methods, illustrating them through visual representations of data and models. The proposed training is suitable for a general …


Temporal Trends In Mortality Related To Stroke And Atrial Fibrillation In The United States: A 21-Year Retrospective Analysis Of Cdc-Wonder Database, Owais Ahmad, Hanzala Ahmed Farooqi, Isra Ahmed, Adeena Jamil, Rayyan Nabi, Irfan Ullah, Abdul Wali Khan, Raheel Ahmed, Mahboob Alam, Bernardo Cortese, Mamas A Mamas Dec 2024

Temporal Trends In Mortality Related To Stroke And Atrial Fibrillation In The United States: A 21-Year Retrospective Analysis Of Cdc-Wonder Database, Owais Ahmad, Hanzala Ahmed Farooqi, Isra Ahmed, Adeena Jamil, Rayyan Nabi, Irfan Ullah, Abdul Wali Khan, Raheel Ahmed, Mahboob Alam, Bernardo Cortese, Mamas A Mamas

Faculty, Staff and Students Publications

Aims: Atrial Fibrillation (AF) is one of the most strongly associated risk factors for stroke. Our study aims to analyze changes in mortality from 1999 to 2020 in patients with AF and stroke.

Methods: Using the Centre for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER), we retrospectively analyzed annual age-adjusted mortality rates (AAMR) per million from 1999 to 2020 in stroke patients with AF. Temporal trends were analyzed, and Annual Percentage Change (APC) was calculated using the JoinPoint regression model across variations in demographics (sex, race) and regional subgroups.

Results: Around 490 000 deaths were reported …


Meta-Analysis Of Longitudinal Comparison Of Transcatheter Versus Surgical Aortic Valve Replacement In Patients At Low To Intermediate Surgical Risk, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Zain A Nadeem, Fariha Arif, Eeshal Zulfiqar, Muhammad H Kazmi, Rukesh Yadav, Hritvik Jain, Raheel Ahmed, Mahboob Alam, Farhan Shahid Dec 2024

Meta-Analysis Of Longitudinal Comparison Of Transcatheter Versus Surgical Aortic Valve Replacement In Patients At Low To Intermediate Surgical Risk, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Zain A Nadeem, Fariha Arif, Eeshal Zulfiqar, Muhammad H Kazmi, Rukesh Yadav, Hritvik Jain, Raheel Ahmed, Mahboob Alam, Farhan Shahid

Faculty, Staff and Students Publications

Background: Surgical aortic valve replacement (SAVR) is the commonly used approach for aortic valve replacement (AVR) in patients with aortic stenosis at low or intermediate surgical risk. However, transcatheter aortic valve replacement (TAVR) has emerged as an alternative to SAVR for AVR. This meta-analysis aims to assess the comparative efficacy and safety of TAVR versus SAVR in low-to-intermediate surgical risk patients by analyzing temporal trends in the outcomes of TAVR and SAVR at various follow-up intervals, providing a more detailed understanding.

Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception up to …


Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony Dec 2024

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …


Fournier's Gangrene Severity Index And Charlson Comorbidity Index Predict Mortality, Intensive Care Unit Admission, And Length Of Hospital Stay In Patients With Fournier's Gangrene: An Analysis Of 264 Consecutive Patients, Nicholas Hauser, Chenlin Huang, Girija Vaidya, Timothy Chrusciel, Krithika Narayana Kumarasan, John Culhane, Sameer Siddiqui Dec 2024

Fournier's Gangrene Severity Index And Charlson Comorbidity Index Predict Mortality, Intensive Care Unit Admission, And Length Of Hospital Stay In Patients With Fournier's Gangrene: An Analysis Of 264 Consecutive Patients, Nicholas Hauser, Chenlin Huang, Girija Vaidya, Timothy Chrusciel, Krithika Narayana Kumarasan, John Culhane, Sameer Siddiqui

Faculty, Staff and Students Publications

Introduction

Fournier’s gangrene (FG) is a rapidly progressing necrotizing fasciitis. The Fournier's Gangrene Severity Index (FGSI), in conjunction with the Charlson Comorbidity Index (CCI), has been used as a mortality predictor during hospitalization. Patients with diabetes have also been shown to be at an increased risk for the development of FG. This study explores the potential of using FGSI, CCI, and patient diabetes status in predicting more extensive patient outcomes, including intensive care unit (ICU) admission and length of hospital stay.

Methods

From 2013 to 2023, inpatient admissions with the diagnosis of FG were selected from the EPIC Clarity database …


Comparison Of Predicted And Actual Dermatitis Generated From Computed Tomography Images And Dose Distribution Maps, Yasuhide Miyabe, Saori Oshiro, Hiroto Seki, Yusuke Muroi, Eriko Kawashima, Megumi Hosoda, Kento Ohashi, Hiromu Yamanaka, Mingliang Shao, Hiromi Sugawara, Jyunetsu Mizoe, Ritsuko Komaki Dec 2024

Comparison Of Predicted And Actual Dermatitis Generated From Computed Tomography Images And Dose Distribution Maps, Yasuhide Miyabe, Saori Oshiro, Hiroto Seki, Yusuke Muroi, Eriko Kawashima, Megumi Hosoda, Kento Ohashi, Hiromu Yamanaka, Mingliang Shao, Hiromi Sugawara, Jyunetsu Mizoe, Ritsuko Komaki

Faculty, Staff and Students Publications

Anticipating the onset, location and severity of radiation dermatitis before radiotherapy can aid in dermatological care. This study developed a method for creation of a prediction diagram for dermatitis and conducted a comparative verification between the prediction diagram and actual patient condition. The prediction diagram involved converting skin doses into 2 Gy fractionated equivalent doses using α/β of 10.0, defining regions of interest (ROIs) from 20-50 Gy at 10 Gy intervals. Overlaps between these ROIs at each dose level and the skin (external) was sequentially color-coded as blue, yellow, red, and purple. The study included four patients: two underwent head …


Predicting Operative Mortality In Patients Who Undergo Elective Open Thoracoabdominal Aortic Aneurysm Repair, Kyle W Blackburn, Susan Y Green, Allen Kuncheria, Meng Li, Adel M Hassan, Brittany Rhoades, Scott A Weldon, Subhasis Chatterjee, Marc R Moon, Scott A Lemaire, Joseph S Coselli Dec 2024

Predicting Operative Mortality In Patients Who Undergo Elective Open Thoracoabdominal Aortic Aneurysm Repair, Kyle W Blackburn, Susan Y Green, Allen Kuncheria, Meng Li, Adel M Hassan, Brittany Rhoades, Scott A Weldon, Subhasis Chatterjee, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Background

We have developed a model aimed at identifying preoperative predictors of operative mortality in patients who undergo elective, open thoracoabdominal aortic aneurysm (TAAA) repair. We converted this model into an intuitive nomogram to aid preoperative counseling.

Methods

We retrospectively analyzed data from 2884 elective, open TAAA repairs performed between 1986 and 2023 in a single practice. Using clinical and selected operative variables, we built 4 predictive models: multivariable logistic regression (MLR), random forest, support vector machine, and gradient boosting machine. Each model’s predictive effectiveness was evaluated with the C-statistic. Test C-statistics were computed using an 80:20 cross-validation scheme with …


Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin Dec 2024

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …


Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll Dec 2024

Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which …


The Clinical Efficacy And Safety Of Bempedoic Acid In Patients At Elevated Risk Of Cardiovascular Disease: A Meta-Analysis Of Randomized Clinical Trials, Ahmed Sayed, Omar Shazly, Leandro Slipczuk, Chayakrit Krittanawong, Farhala Baloch, Salim S Virani Dec 2024

The Clinical Efficacy And Safety Of Bempedoic Acid In Patients At Elevated Risk Of Cardiovascular Disease: A Meta-Analysis Of Randomized Clinical Trials, Ahmed Sayed, Omar Shazly, Leandro Slipczuk, Chayakrit Krittanawong, Farhala Baloch, Salim S Virani

Faculty, Staff and Students Publications

Purpose: Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent.

Methods: We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I2 measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version …


Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne Dec 2024

Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne

Faculty, Staff and Students Publications

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Method: Qualitative interviews were conducted with veterans (n=15) with PTSD who had received at least 2 sessions of a TF-EBP.

Measures: Survey …


Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek Dec 2024

Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek

Faculty, Staff and Students Publications

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, …


Template-Assisted Covalent Modification Underlies Activity Of Covalent Molecular Glues, Yen-Der Li, Michelle W Ma, Muhammad Murtaza Hassan, Moritz Hunkeler, Mingxing Teng, Kedar Puvar, Justine C Rutter, Ryan J Lumpkin, Brittany Sandoval, Cyrus Y Jin, Anna M Schmoker, Scott B Ficarro, Hakyung Cheong, Rebecca J Metivier, Michelle Y Wang, Shawn Xu, Woong Sub Byun, Brian J Groendyke, Inchul You, Logan H Sigua, Isidoro Tavares, Charles Zou, Jonathan M Tsai, Paul M C Park, Hojong Yoon, Felix C Majewski, Haniya T Sperling, Jarrod A Marto, Jun Qi, Radosław P Nowak, Katherine A Donovan, Mikołaj Słabicki, Nathanael S Gray, Eric S Fischer, Benjamin L Ebert Dec 2024

Template-Assisted Covalent Modification Underlies Activity Of Covalent Molecular Glues, Yen-Der Li, Michelle W Ma, Muhammad Murtaza Hassan, Moritz Hunkeler, Mingxing Teng, Kedar Puvar, Justine C Rutter, Ryan J Lumpkin, Brittany Sandoval, Cyrus Y Jin, Anna M Schmoker, Scott B Ficarro, Hakyung Cheong, Rebecca J Metivier, Michelle Y Wang, Shawn Xu, Woong Sub Byun, Brian J Groendyke, Inchul You, Logan H Sigua, Isidoro Tavares, Charles Zou, Jonathan M Tsai, Paul M C Park, Hojong Yoon, Felix C Majewski, Haniya T Sperling, Jarrod A Marto, Jun Qi, Radosław P Nowak, Katherine A Donovan, Mikołaj Słabicki, Nathanael S Gray, Eric S Fischer, Benjamin L Ebert

Faculty, Staff and Students Publications

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’. We identified a new series of BRD4 molecular glue degraders that recruit CUL4DCAF16 ligase to the second bromodomain of BRD4 (BRD4BD2). Through comprehensive biochemical, structural and mutagenesis analyses, we elucidated how pre-existing structural complementarity between DCAF16 and BRD4BD2 serves as a template to optimally orient the degrader for covalent modification of DCAF16Cys58. This process stabilizes …


Google Trends And Syphilis, Theodore Rosen, Maci Terrell Dec 2024

Google Trends And Syphilis, Theodore Rosen, Maci Terrell

Faculty, Staff and Students Publications

Objective: This study aims to assess the correlation between Centers for Disease Control-reported syphilis incidence rates and case burden and public interest in syphilis as indicated by Google search trends.

Methods: This study utilized Google Trends data to analyze popular syphilis-related search terms from 2013 to 2023. The latest Centers for Disease Control-reported syphilis incidence rates for 2022 were compared to Google Trends data to identify patterns or correlations.

Results: Google Trends data showed a 37.65-percent increase in average annual searches for syphilis-related terms in the United States from 2013 to 2023. The largest increase in search volume was observed …


Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day Dec 2024

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …


Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso Dec 2024

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …


Cadasil: A Notch3-Associated Cerebral Small Vessel Disease, Lamei Yuan, Xiangyu Chen, Joseph Jankovic, Hao Deng Dec 2024

Cadasil: A Notch3-Associated Cerebral Small Vessel Disease, Lamei Yuan, Xiangyu Chen, Joseph Jankovic, Hao Deng

Faculty, Staff and Students Publications

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of …


Supporting Cancer-Related Fatigue Self-Management: A Conversation Analytic Study Of Nurse Counsellor And Cancer Survivor Consultations, Oluwaseyifunmi Andi Agbejule, Stuart Ekberg, Nicolas H. Hart, Raymond J. Chan Dec 2024

Supporting Cancer-Related Fatigue Self-Management: A Conversation Analytic Study Of Nurse Counsellor And Cancer Survivor Consultations, Oluwaseyifunmi Andi Agbejule, Stuart Ekberg, Nicolas H. Hart, Raymond J. Chan

Research outputs 2022 to 2026

Purpose: Cancer-related fatigue (CRF) is a prevalent and distressing symptom experienced by people affected by cancer. A breakdown of the clinician-patient partnership and suboptimal clinician communication has been identified as a significant barrier to implementing into clinical practice effective self-management strategies for CRF. This study examined the use and impact of communication practices employed by trained cancer nurse counsellors when providing CRF self-management support to cancer survivors.

Methods: Interactions from 41 telehealth consultations between three nurse counsellors and 23 cancer survivors in a CRF self-management support clinic in Queensland, Australia were recorded and analysed using conversation analysis methods.

Results: Analysis …


Meeting Aerobic Physical Activity Guidelines And Associations With Physical Fitness In Men With Metastatic Prostate Cancer: Baseline Results Of The Multicentre Interval-Gap4 Trial, Lisa Umlauff, Stacey A. Kenfield, Robert U. Newton, Nicolas H. Hart, Fred Saad, Kerry S. Courneya, Rosemary Greenwood, Wilhelm Bloch, Moritz Schumann Dec 2024

Meeting Aerobic Physical Activity Guidelines And Associations With Physical Fitness In Men With Metastatic Prostate Cancer: Baseline Results Of The Multicentre Interval-Gap4 Trial, Lisa Umlauff, Stacey A. Kenfield, Robert U. Newton, Nicolas H. Hart, Fred Saad, Kerry S. Courneya, Rosemary Greenwood, Wilhelm Bloch, Moritz Schumann

Research outputs 2022 to 2026

Background: This study compared the physical activity level of men with metastatic prostate cancer at baseline of the multicentre INTERVAL-GAP4 trial to the American Cancer Society guidelines and examined associations with physical fitness. Methods: A total of 140 men on androgen deprivation therapy (ADT) were included in this cross-sectional analysis of baseline data from the INTERVAL-GAP4 trial. Exclusion criteria included a maximum of 1 h of vigorous aerobic exercise or one structured resistance exercise session per week but no restrictions on habitual physical activity. Moderate-to-vigorous physical activity (MVPA) was assessed using a modified Godin–Shephard Leisure-Time Physical Activity Questionnaire. Physical fitness …


Planning And Evaluating An Integrated Clinical Exercise Oncology Service: An Exploratory Mixed-Methods Study, Ciaran M. Fairman, Shana E. Harrington, Alec R. Schumpp, Alex M. Brooks, Morgan J. Jones, Julian Kim, Mary A. Kennedy Dec 2024

Planning And Evaluating An Integrated Clinical Exercise Oncology Service: An Exploratory Mixed-Methods Study, Ciaran M. Fairman, Shana E. Harrington, Alec R. Schumpp, Alex M. Brooks, Morgan J. Jones, Julian Kim, Mary A. Kennedy

Research outputs 2022 to 2026

Background: This project aimed to design and evaluate the potential to integrate an exercise oncology service into clinical care in a local healthcare system. The goal was to inform the design of an implementation strategy to promote its sustainable use in standard care. Methods: This two-phase, exploratory study used a mixed-methods approach. First, qualitative measures were used to understand the context for exercise integration into oncology care by clinicians and administrators in the healthcare system. Next, the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework guided a comprehensive evaluation of the exercise service. Reach and Adoption were measured via number of …


Role Of N-Glycosylation In Gastrointestinal Cancers, Ruirui Xu, Lois Balmer, Gengzhen Chen, Manshu Song Dec 2024

Role Of N-Glycosylation In Gastrointestinal Cancers, Ruirui Xu, Lois Balmer, Gengzhen Chen, Manshu Song

Research outputs 2022 to 2026

Gastrointestinal cancers pose a significant global health challenge. N-glycosylation modulates various cellular processes, including key cancer-related mechanisms. Elucidating its involvement in the onset and advancement of these cancers can offer critical insights for enhancing diagnostic and therapeutic approaches. This review outlines the core process of protein N-glycosylation and highlights its contribution to the progression of gastrointestinal cancers, encompassing cell proliferation, survival, invasion, metastasis, and immune evasion, mainly through its impact on critical signaling pathways. Notably, aberrant N-glycosylation patterns have emerged as crucial biomarkers for the diagnosis and prognosis of various gastrointestinal cancers, providing the foundation for more personalized therapeutic approaches. …


Characteristics Of High-Risk Bipolar Bone Loss Lesions Using 3-Dimensional Imaging, Petar Golijanin, Justin Arner, Claire Ryan, Qais Zai, Liam Peebles, Annalise Peebles, Phob Ganokroj, Ryan Whalen, Stephanie Eble, Danielle Rider, Srdjan Ninković, Matthew Provencher Dec 2024

Characteristics Of High-Risk Bipolar Bone Loss Lesions Using 3-Dimensional Imaging, Petar Golijanin, Justin Arner, Claire Ryan, Qais Zai, Liam Peebles, Annalise Peebles, Phob Ganokroj, Ryan Whalen, Stephanie Eble, Danielle Rider, Srdjan Ninković, Matthew Provencher

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The concept of on-track versus off-track bone lesions in glenohumeral instability continues to evolve. Although much has been ascertained from an original biomechanical model, bony pathological changes, especially on 3-dimensional (3D) imaging, have not been fully evaluated.

PURPOSE: To compare the differences in on-track versus off-track lesions to characterize glenoid and humeral head bone defects using 3D modeling software.

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS:A consecutive cohort of 75 patients with recurrent anterior instability, with evidence of Hill-Sachs lesions (HSLs) and
glenoid bone loss (GBL) and a mean age of 27.1 years (range, 18-48 years), were …


What Is The Evidence? Updates In The Use Of Antenatal Corticosteroids For Patients At Risk Of Preterm Birth, Moti Gulersen, Cynthia Gyamfi-Bannerman Dec 2024

What Is The Evidence? Updates In The Use Of Antenatal Corticosteroids For Patients At Risk Of Preterm Birth, Moti Gulersen, Cynthia Gyamfi-Bannerman

Department of Obstetrics and Gynecology Faculty Papers

Antenatal corticosteroids have long been considered one of the most important antenatal therapies available for pregnant patients at risk of preterm birth based on the associated reduction of neonatal morbidity and mortality following their administration. However, despite decades of research since their incorporation into routine clinical practice, a number of key questions related to antenatal corticosteroid use remain. These include evaluating the impact of antenatal corticosteroids at gestational ages outside of the previously recommended window of 24 0/7–33 6/7 weeks of gestation, determining factors associated with optimal steroid timing in order to reduce unnecessary exposure, alterations in its dosing regimen, …


Mammalian Mitochondrial Inorganic Polyphosphate (Polyp) And Cell Signaling: Crosstalk Between Polyp And The Activity Of Ampk, Renata T. Da Costa, Anna Nichenko, Matheus M. Perez, Malgorzata Tokarska-Schlattner, Sheida Kavehmoghaddam, Vedangi Hambardikar, Ernest R. Scoma, Erin L. Seifert, Uwe Schlattner, Joshua C. Drake, Maria E. Solesio Nov 2024

Mammalian Mitochondrial Inorganic Polyphosphate (Polyp) And Cell Signaling: Crosstalk Between Polyp And The Activity Of Ampk, Renata T. Da Costa, Anna Nichenko, Matheus M. Perez, Malgorzata Tokarska-Schlattner, Sheida Kavehmoghaddam, Vedangi Hambardikar, Ernest R. Scoma, Erin L. Seifert, Uwe Schlattner, Joshua C. Drake, Maria E. Solesio

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

UNLABELLED: Inorganic polyphosphate (polyP) is an evolutionary and ancient polymer composed by orthophosphate units linked by phosphoanhydride bonds. In mammalian cells, polyP shows a high localization in mammalian mitochondria, and its regulatory role in various aspects of bioenergetics has already been demonstrated, via molecular mechanism(s) yet to be fully elucidated. In recent years, a role for polyP in signal transduction, from brain physiology to the bloodstream, has also emerged.

OBJECTIVE: In this manuscript, we explored the intriguing possibility that the effects of polyP on signal transduction could be mechanistically linked to those exerted on bioenergetics.

METHODS: To conduct our studies, …


Impact Of Chatgpt And Large Language Models On Radiology Education: Association Of Academic Radiology-Radiology Research Alliance Task Force White Paper, David H. Ballard, Alexander Antigua-Made, Emily Barre, Elizabeth Edney, Emile B. Gordon, Linda Kelahan, Taha Lodhi, Jonathan G. Martin, Melis Ozkan, Kevin Serdynski, Bradley Spieler, Daphne Zhu, Scott J. Adams Nov 2024

Impact Of Chatgpt And Large Language Models On Radiology Education: Association Of Academic Radiology-Radiology Research Alliance Task Force White Paper, David H. Ballard, Alexander Antigua-Made, Emily Barre, Elizabeth Edney, Emile B. Gordon, Linda Kelahan, Taha Lodhi, Jonathan G. Martin, Melis Ozkan, Kevin Serdynski, Bradley Spieler, Daphne Zhu, Scott J. Adams

School of Medicine Faculty Publications

Generative artificial intelligence, including large language models (LLMs), holds immense potential to enhance healthcare, medical education, and health research. Recognizing the transformative opportunities and potential risks afforded by LLMs, the Association of Academic Radiology-Radiology Research Alliance convened a task force to explore the promise and pitfalls of using LLMs such as ChatGPT in radiology. This white paper explores the impact of LLMs on radiology education, highlighting their potential to enrich curriculum development, teaching and learning, and learner assessment. Despite these advantages, the implementation of LLMs presents challenges, including limits on accuracy and transparency, the risk of misinformation, data privacy issues, …


Crosstalk Of Pyroptosis And Cytokine In The Tumor Microenvironment: From Mechanisms To Clinical Implication, Hua Wang, Tao Wang, Shuxiang Yan, Jinxin Tang, Yibo Zhang, Liming Wang, Haodong Xu, Chao Tu Nov 2024

Crosstalk Of Pyroptosis And Cytokine In The Tumor Microenvironment: From Mechanisms To Clinical Implication, Hua Wang, Tao Wang, Shuxiang Yan, Jinxin Tang, Yibo Zhang, Liming Wang, Haodong Xu, Chao Tu

Faculty, Staff and Student Publications

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex …