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Decreased Proliferation Of Hepg2 Liver Cancer Cells In Vitro And Exhibited Proteomic Changes In Vivo In Subjects With Metabolic Syndrome And Metabolic Dysfunction-Associated Steatotic Liver Disease Who Performed Four-Week Dawn-To-Dusk Dry Fasting, Ayse L Mindikoglu, Kristin Eckel-Mahan, Antone R Opekun, Mustafa M Alzubaidi, Zoe R Crochet, Prasun K Jalal, Sung Yun Jung Jun 2025

Decreased Proliferation Of Hepg2 Liver Cancer Cells In Vitro And Exhibited Proteomic Changes In Vivo In Subjects With Metabolic Syndrome And Metabolic Dysfunction-Associated Steatotic Liver Disease Who Performed Four-Week Dawn-To-Dusk Dry Fasting, Ayse L Mindikoglu, Kristin Eckel-Mahan, Antone R Opekun, Mustafa M Alzubaidi, Zoe R Crochet, Prasun K Jalal, Sung Yun Jung

The Brown Foundation: Institute of Molecular Medicine

Background: Four-week dawn-to-dusk dry fasting (DDDF) was previously shown to have a potent anti-inflammatory effect and induce an anti-tumorigenic proteome in the serum and peripheral blood mononuclear cells in subjects without cancer. The study goal was to determine if serum obtained from these subjects without cancer who underwent 4-week DDDF has an anti-tumorigenic effect.

Methods: HepG2 cells were treated with serum collected from four individuals with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) and four healthy individuals who performed 4-week DDDF. The objective was to assess cell proliferation/viability in HepG2 cells treated with non-fasted and dry-fasted serum and …


Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo Jun 2025

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …


Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo Jun 2025

Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo

Faculty, Staff and Student Publications

Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family …


The Only Constant Is Change: The Role Of Genetic Diversification In Cancer And Beyond, Malgorzata Tyczynska Weh Jun 2025

The Only Constant Is Change: The Role Of Genetic Diversification In Cancer And Beyond, Malgorzata Tyczynska Weh

USF Tampa Graduate Theses and Dissertations

Genetic diversification, the process by which genetic variation arises in a population, is fundamental to evolution by natural selection. Mutation, a central diversification process, fuels adaptation across species, including in cancer. Yet most new mutations are neutral or deleterious on cell fitness, raising the question of how mutation-driven adaptation persists. To explore this paradox, I developed a spatial agent-based model (ABM) in which population fitness emerges from individual cells acquiring mutations at varied rates and with diverse fitness effects. I evaluated model behavior across adaptive states, mutation rates, and distributions of fitness effects. The results show that high mutation rates …


Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz Jun 2025

Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz

Faculty, Staff and Student Publications

Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.

Aims and methods: The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. …


Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala Jun 2025

Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Collagen II is a vital structural component in developing bones and mature cartilage. Muta- tions in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in colla- gen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before …


Agenda (Pdf), Department Of Orthopaedic Surgery Jun 2025

Agenda (Pdf), Department Of Orthopaedic Surgery

Dept. of Orthopaedics: Robert D. D’Ambrosia Lectureship & Research Day

No abstract provided.


Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park Jun 2025

Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park

Faculty, Staff and Student Publications

Lung endothelial cells (LuECs) play crucial roles in lung regeneration and support lung organoids (LOs). However, detailed guidelines for LO culture using LuECs have not been reported yet. Here, we present an efficient protocol for generating and culturing murine LOs that mimic regeneration. We describe steps for the isolation of LuECs and lung epithelial cells, followed by LO culture. We also describe how to establish genetically engineered LOs using viral transduction. For complete details on the use and execution of this protocol, please refer to Kim et al.


Usp37 Counteracts Hltf To Protect Damaged Replication Forks And Promote Survival Of Brca1-Deficient Cells And Parp Inhibitor Resistance, Mengfan Tang, Siting Li, Ziqiang Zhu, Chao Wang, Shuai Ding, Huimin Zhang, Min Huang, Sarah Keast, Zhen Chen, Ling Yin, Litong Nie, Dan Su, Xu Feng, Junjie Chen Jun 2025

Usp37 Counteracts Hltf To Protect Damaged Replication Forks And Promote Survival Of Brca1-Deficient Cells And Parp Inhibitor Resistance, Mengfan Tang, Siting Li, Ziqiang Zhu, Chao Wang, Shuai Ding, Huimin Zhang, Min Huang, Sarah Keast, Zhen Chen, Ling Yin, Litong Nie, Dan Su, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPi) have greatly improved survival of cancer patients harboring BRCA1 mutations. However, therapy resistance develops via either restoration of homologous recombination or replication fork stabilization. Therapeutic targets to overcome PARPi resistance are critically needed. We identified the deubiquitinase USP37 as a key determinant of PARPi toxicity in BRCA1-deficient cells via whole-genome CRISPR screens. USP37 ablation enhanced PARPi sensitivity in BRCA1-deficient cells and also overcame PARPi resistance due to 53BP1 loss. USP37 interacts with and deubiquitinates replication protein A (RPA) at stalled replication forks to limit excessive RPA accumulation, progressive RPA exhaustion, and the conversion of RPA-coated single-stranded …


Protocol To Analyze Trna And Rrna Processing Using Biotin-Labeled Probes, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt Jun 2025

Protocol To Analyze Trna And Rrna Processing Using Biotin-Labeled Probes, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

Mature tRNAs and rRNAs are derived from larger precursor transcripts through intricate endo- and exonuclease processing steps. Here, we present a protocol to analyze rRNA and tRNA processing using total RNA extracted from human cells. We describe steps for separating RNA by denaturing electrophoresis, followed by northern blotting. We detail procedures for detecting pre-rRNA intermediates or specific tRNA species using biotin-labeled probes imaged via fluorescence or chemiluminescence. This non-radioactive, high-sensitivity assay enables the investigation of rRNA and tRNA expression dynamics. For complete details on the use and execution of this protocol, please refer to Hwang et al.


Topical Lifitegrast Therapy For Dry Eye Disease, Lama Assi, Salim C. Lutfallah, Tsz Wing Yim, Su Hsun Liu, Sharon J. Duffy, Jayne Weiss Jun 2025

Topical Lifitegrast Therapy For Dry Eye Disease, Lama Assi, Salim C. Lutfallah, Tsz Wing Yim, Su Hsun Liu, Sharon J. Duffy, Jayne Weiss

School of Medicine Faculty Publications

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effectiveness and safety of topical lifitegrast therapy alone or in combination with artificial tears, compared with a placebo, artificial tears alone, or no treatment for dry eye disease.


Primary Mouse Choroidal Endothelial Cell Culture, Qiuhua Yang, Yongfeng Cai, Qian Ma, Yuqing Huo Jun 2025

Primary Mouse Choroidal Endothelial Cell Culture, Qiuhua Yang, Yongfeng Cai, Qian Ma, Yuqing Huo

Faculty, Staff and Students Publications

The study of choroidal endothelial cells is essential for understanding the pathological mechanisms underlying choroidal neovascularization and other vision-threatening disorders. Traditional methods for isolating and culturing primary endothelial cells often yield mixed populations or require specialized equipment, limiting their widespread use. Here, we present a straightforward protocol for isolating and culturing primary mouse choroidal endothelial cells. This protocol involves enzymatic digestion of choroidal tissue, magnetic-activated cell sorting (MACS) to enrich CD31+ endothelial cells, and optimized culture conditions to promote cell proliferation and maintain endothelial phenotype. The protocol is strategic, reproducible, and requires minimal specialized equipment, making it accessible for researchers …


Efficacy And Safety Of Olezarsen In Dyslipidemia: A Systematic Review And Dose-Response Meta-Analysis Of Randomized Controlled Trials, Christopher D. Tristan, Risalina Myrtha, Matthew A. Wijayanto, Erlangga M. Kynaya, Muhammad F. Hamka, Nathania E. Sudiono, Muhammad A. Rusyidi, Muhana F. Ilyas Jun 2025

Efficacy And Safety Of Olezarsen In Dyslipidemia: A Systematic Review And Dose-Response Meta-Analysis Of Randomized Controlled Trials, Christopher D. Tristan, Risalina Myrtha, Matthew A. Wijayanto, Erlangga M. Kynaya, Muhammad F. Hamka, Nathania E. Sudiono, Muhammad A. Rusyidi, Muhana F. Ilyas

Journal of the Saudi Heart Association

Olezarsen emerged as a novel promising Apo-C3 inhibitor for dyslipidemia. However, its dose-response relationship remains uncertain. This review aims to evaluate the lipid-lowering effect of olezarsen, safety measures, and dose-response effects to determine the optimal dose. A systematic search was conducted across Scopus, PubMed, ScienceDirect, and CENTRAL on January 2, 2025. Randomized controlled trial (RCT) comparing olezarsen with placebo in dyslipidemia was included. The Rob 2.0 tool was implemented to assess quality. R-studio and STATA were used to conduct statistical analysis. From a total of 194 documents at initial search, four RCTs involving 361 patients were included in the present …


Comparison Of Delta Neutrophil Index And Inflammatory Markers In The Diagnosis Of Late-Onset Neonatal Sepsis In Preterm Infants, Aybuke Yazici, Hayriye Gozde Kanmaz Kutman, Gulsum Kadioglu Simsek, Betul Siyah Bilgin, Fuat Emre Canpolat, Bedia Dinc, Serife Suna Oguz Jun 2025

Comparison Of Delta Neutrophil Index And Inflammatory Markers In The Diagnosis Of Late-Onset Neonatal Sepsis In Preterm Infants, Aybuke Yazici, Hayriye Gozde Kanmaz Kutman, Gulsum Kadioglu Simsek, Betul Siyah Bilgin, Fuat Emre Canpolat, Bedia Dinc, Serife Suna Oguz

Journal of Pediatric Infectious Diseases

Objective: To assess the performance of the relatively new hematological marker delta neutrophil index (DNI) and other inflammatory markers in proven sepsis of the very preterm infant.

Methods: Infants with a gestational age of <32 weeks and examined for suspected late-onset sepsis (LOS) were evaluated retrospectively. Demographic characteristics, laboratory findings, and neonatal morbidity and mortality were compared between infants with blood culture-confirmed sepsis and clinical sepsis.

Results: The study included 358 infants, 90 with proven sepsis and 268 with clinical sepsis. The mean gestational ages in these groups were 28.2±2 and 28.2±2.1 weeks, and the mean birth weight was 1139±372 and 1148±370 g, respectively (p>0.05). The proven sepsis group had higher DNI (median 7.1% [range, 0.1-74] vs. 0.6% [range, 0.1-24.7%], p<0.01], CRP (median 5 [range, 1-38] mg/L vs. 1 [range, 1-15] mg/L, p<0.001), interleukin 6 (median 620 [range, 6.9-5500] pg/mL vs. 42.2 [range, 2.2-5500] pg/mL, p<0.01), and procalcitonin (median 6.2 [range, 0.26-86] μg/L vs. 0.6 [range, 0.06-25.7] μg/L, p=0.002). According to ROC analysis, interleukin 6 had the highest area under the curve (AUC) at 0.74 (95% CI 0.60-0.88, p<0.01). The AUC values were 0.73 (95% CI 0.59-0.88, p=0.01) for procalcitonin, 0.62 (95% CI 0.44-0.80, p=0.18) for DNI, and 0.66 (95% CI 0.50-0.82, p=0.05) for CRP.

Conclusion: The delta neutrophil index showed a statistically significant elevation …


Diagnostic Value Of Lncrna Fgd5-As1 Sponge Mir-223-3p In Infantile Pneumonia And Its Prognostic Effect On Rehabilitation, Hong-Ping Ren, Hong-Lin Wen, Ya-Nan Liu, Lin Cai Jun 2025

Diagnostic Value Of Lncrna Fgd5-As1 Sponge Mir-223-3p In Infantile Pneumonia And Its Prognostic Effect On Rehabilitation, Hong-Ping Ren, Hong-Lin Wen, Ya-Nan Liu, Lin Cai

Journal of Pediatric Infectious Diseases

Objective: This study aimed to uncover the value of long non-coding RNA FGD5-AS1 (lncRNA FGD5-AS1) in the diagnosis of infantile pneumonia and explore its pathological mechanism in lung fibroblasts. This research may provide a potential biomarker for diagnosing patients and predicting their rehabilitation outcomes.

Methods: This study included 92 children with infantile pneumonia as the research object, and an equal number of healthy children were introduced as controls. The FGD5-AS1 content was detected using real-time quantitative polymerase chain reaction (RT-qPCR) assay. The diagnostic value of FGD5-AS1 was evaluated by receiver operating characteristic (ROC) and logistic analysis. The molecular mechanism of …


Epidemiology Of Acute Infectious Diarrhea-Associated Viruses In Children In Hangzhou, China, 2023, Ya-Jun Guo, Lin Li, Qin-Rui Lai, Wei Li Jun 2025

Epidemiology Of Acute Infectious Diarrhea-Associated Viruses In Children In Hangzhou, China, 2023, Ya-Jun Guo, Lin Li, Qin-Rui Lai, Wei Li

Journal of Pediatric Infectious Diseases

Objective: To investigate the epidemiological characteristics of children infected with diarrheal virus in Hangzhou, China, 2023.

Methods: From January 2023 to December 2023, 20,939 stool samples from children with acute infectious diarrhea were collected for detection of rotavirus A and human adenovirus, using Latex agglutination detection kits; 7584 stool samples were collected for detection of norovirus, using real‐time PCR reagent.

Results: 639 (3.0%, 639/20,939) tested positive for rotavirus A, and 1,201 (5.7%, 1,201/20,939) positive samples were detected by Colloidal gold method. The positive rates of norovirus were 42.2% (3,203/7,585). Among all age groups, the rotavirus A positive detection rate was …


Risk Factors For Serious Bacterial Infections Among Young Infants With Hypothermia: Protocol For A Multicenter, Retrospective Case-Control Study, Sriram Ramgopal, Paul Aronson, Douglas Lorenz, Alexander Joseph Rogers, Andrea Tania Cruz Jun 2025

Risk Factors For Serious Bacterial Infections Among Young Infants With Hypothermia: Protocol For A Multicenter, Retrospective Case-Control Study, Sriram Ramgopal, Paul Aronson, Douglas Lorenz, Alexander Joseph Rogers, Andrea Tania Cruz

Faculty, Staff and Students Publications

Background: Hypothermia in young infants presenting to the emergency department (ED) may indicate a serious bacterial infection (SBI) such as a urinary tract infection, bacteremia, or bacterial meningitis. Improved understanding of the epidemiology of SBI in infants with hypothermia and the development of prediction models can help avoid unnecessary invasive procedures and antimicrobial exposure.

Objective: The aim of the study is to (1) describe the epidemiology of SBI and herpes simplex virus (HSV) among infants with hypothermia, (2) assess the role of biomarkers in predicting SBI, and (3) derive and internally validate a multivariable predictive model for SBI among infants …


From Er To Mortality In 48 Hours: A Fatal Case Of Overwhelming Post-Splenectomy Infection, Miriam Stern, Ba, Blaise O’Malley, Bs, Amry Majeed, Md, Michael Grodsky, Md Jun 2025

From Er To Mortality In 48 Hours: A Fatal Case Of Overwhelming Post-Splenectomy Infection, Miriam Stern, Ba, Blaise O’Malley, Bs, Amry Majeed, Md, Michael Grodsky, Md

The Medicine Forum

Overwhelming post-splenectomy infection (OPSI) is a known complication of asplenia.1,2 While the precise rates of morbidity and mortality are unknown, estimates range from 38% to as high as 70%.2 Because the spleen plays an important role in protecting against infections with encapsulated microorganisms, OPSI is most commonly caused by infection with encapsulated bacteria, specifically Streptococcus pneumoniae.1–3 While pneumococcal vaccines have been shown to improve immunogenicity in asplenic people, OPSI remains a danger to both vaccinated and unvaccinated patients.4,5 Additional measures to protect asplenic patients from overwhelming infection have been proposed, but the evidence remains mixed. …


Case Report Of Gastritis As A Complication Of Immunotherapy Treatment Of Metastatic Endometrial Cancer With Lenvatinib And Pembrolizumab, Bret Mccarty, Md, Nia Johnson, Bs, Suchit Bhutani, Md Jun 2025

Case Report Of Gastritis As A Complication Of Immunotherapy Treatment Of Metastatic Endometrial Cancer With Lenvatinib And Pembrolizumab, Bret Mccarty, Md, Nia Johnson, Bs, Suchit Bhutani, Md

The Medicine Forum

Immune checkpoint inhibitors (ICIs), such as pembrolizumab (a PD-1 inhibitor), have been shown to be effective in the treatment of a variety of malignancies, including progressive endometrial cancer. ICIs help to activate the patient’s immune system to attack neoplastic cells. However, this immune activation can trigger autoimmune side effects throughout the body, known as immune-related adverse events (irAEs). Immunotherapyassociated hepatitis, colitis and diarrhea have been well documented as irAEs, but gastritis is much less common.1 In this case report of immunotherapy-related gastritis, we attempted to better characterize this more rare condition to assist with early recognition and initiation of appropriate …


Racial Disparities In Response To Ibd Directed Therapy In Crohn’S Disease And Ulcerative Colitis: A Single Center Experience, Ananya Venkatesh, Md, Justin Robbins, Md, Zach Breslin, Md, Cuckoo Choudhary, Md Jun 2025

Racial Disparities In Response To Ibd Directed Therapy In Crohn’S Disease And Ulcerative Colitis: A Single Center Experience, Ananya Venkatesh, Md, Justin Robbins, Md, Zach Breslin, Md, Cuckoo Choudhary, Md

The Medicine Forum

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) associated with significant morbidity and mortality. Current clinical guidelines recommend a range of therapies, including tumor necrosis factor alpha (TNFα) antagonists, anti-integrins, interleukin-12/23 (IL12/23) inhibitors, Janus kinase (JAK) inhibitors, and/or corticosteroids for both induction and maintenance of remission. Determining the optimal medication for individual patients can be challenging due to the complexity of treatment options and the need to consider numerous phenotypic factors. While treatment guidelines do not address racial differences explicitly, prior research has highlighted significant phenotypic disparities based on race. This study aims to explore …


Assessment Of The Relationship Between Serum Vitamin D Levels And Its Cardiovascular Outcomes: A Systematic Review And Meta-Analysis Study, Reza Madadi, Sina Bakhshaei, Arian Tavasol, Mahmood Gorjizad, Rouhollah Hemmati, Masood Zangi Jun 2025

Assessment Of The Relationship Between Serum Vitamin D Levels And Its Cardiovascular Outcomes: A Systematic Review And Meta-Analysis Study, Reza Madadi, Sina Bakhshaei, Arian Tavasol, Mahmood Gorjizad, Rouhollah Hemmati, Masood Zangi

Journal of the Saudi Heart Association

Introduction: Cardiovascular events are the most common cause of mortality worldwide. Various studies have shown the relationship between serum 25- hydroxyvitamin D [25(OH) D] levels and cardiovascular events. The purpose of this study is to investigate the meta-analysis of the relationship between serum 25(OH) D levels and the risk of cardiovascular diseases (CVD), including stroke, coronary heart disease, peripheral arterial disease, and aortic disease in the population. Method: Using valid keywords and searching the Medline, Science Direct, Scopus, and web of sciences databases, 22 papers were compiled. Data analysis was performed in the group of people with low serum 25(OH)D …


Slow-Growing Lung Mass In A Patient With Multiple Endocrine Neoplasia Type I: Consider Carcinoid Tumor, Ramin Talebi, Charalambos C. Solomides, Nathaniel R. Evans Iii, Gregory C. Kane Jun 2025

Slow-Growing Lung Mass In A Patient With Multiple Endocrine Neoplasia Type I: Consider Carcinoid Tumor, Ramin Talebi, Charalambos C. Solomides, Nathaniel R. Evans Iii, Gregory C. Kane

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

A 23-year-old man with multiple endocrine neoplasia type 1 (MEN 1) with pancreatic tail masses and Cushing syndrome (status after transsphenoidal adenomectomy) presented with a slow-growing, asymptomatic right lower lung lobe mass confirmed to be an atypical carcinoid tumor by pathologic staging following successful basilar segmentectomy with mediastinal lymphadenectomy. Pulmonary carcinoid tumor (PCT) is a rare neoplasm in patients with MEN 1, but there is limited data on trends in atypical versus typical carcinoid tumors in these patients. This case emphasizes the need to characterize these trends given the implications for metastatic potential and 5-year survival, which can help guide …


Dosimetric Advantage Of Scanning Beam Proton Therapy In Gynecologic Patients Receiving Adjuvant Radiotherapy, Rachel B Ger, Jarrod M Lentz, Joshua S Niedzielski, Sujay A Vora, Martin Bues, Danairis Hernandez Morales, Justin D Anderson, Christopher J Kutyreff, Christie A Schulz, Pedro R Lara, Ana K Ridgway, Pamela R Lemish, Justin D Gagneur, Aman Anand Jun 2025

Dosimetric Advantage Of Scanning Beam Proton Therapy In Gynecologic Patients Receiving Adjuvant Radiotherapy, Rachel B Ger, Jarrod M Lentz, Joshua S Niedzielski, Sujay A Vora, Martin Bues, Danairis Hernandez Morales, Justin D Anderson, Christopher J Kutyreff, Christie A Schulz, Pedro R Lara, Ana K Ridgway, Pamela R Lemish, Justin D Gagneur, Aman Anand

Faculty, Staff and Student Publications

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients.

Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. …


Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser Jun 2025

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …


Proteogenomic Analysis Of The Calgb 40601 (Alliance) Her2+ Breast Cancer Neoadjuvant Trial Reveals Resistance Biomarkers, Eric J Jaehnig, Aranzazu Fernandez-Martinez, Tanmayi D Vashist, Matthew V Holt, Laterrica Williams, Jonathan T Lei, Chang In Moon, Beom-Jun Kim, Yongchao Dou, Haoquan Zhao, Viktoriya Korchina, Richard A Gibbs, Donna Marie Muzny, Harshavardhan Doddapaneni, Charles M Perou, Lisa A Carey, Ana I Robles, Terry Hyslop, Yujia Wen, Linda Mccart, Azra Krek, Francesca Petralia, George Miles, Shyam M Kavuri, Michael A Gillette, D R Mani, Steven A Carr, Bing Zhang, Matthew J Ellis, Shankha Satpathy, Meenakshi Anurag Jun 2025

Proteogenomic Analysis Of The Calgb 40601 (Alliance) Her2+ Breast Cancer Neoadjuvant Trial Reveals Resistance Biomarkers, Eric J Jaehnig, Aranzazu Fernandez-Martinez, Tanmayi D Vashist, Matthew V Holt, Laterrica Williams, Jonathan T Lei, Chang In Moon, Beom-Jun Kim, Yongchao Dou, Haoquan Zhao, Viktoriya Korchina, Richard A Gibbs, Donna Marie Muzny, Harshavardhan Doddapaneni, Charles M Perou, Lisa A Carey, Ana I Robles, Terry Hyslop, Yujia Wen, Linda Mccart, Azra Krek, Francesca Petralia, George Miles, Shyam M Kavuri, Michael A Gillette, D R Mani, Steven A Carr, Bing Zhang, Matthew J Ellis, Shankha Satpathy, Meenakshi Anurag

Faculty, Staff and Students Publications

Proteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer.


Sports And Physical Activity Of Poles In The Context Of Good Health And Well-Being As A Sustainable Development Goal, Elżbieta Biernat, Monika Piątkowska, Robert Podstawski Jun 2025

Sports And Physical Activity Of Poles In The Context Of Good Health And Well-Being As A Sustainable Development Goal, Elżbieta Biernat, Monika Piątkowska, Robert Podstawski

Baltic Journal of Health and Physical Activity

Investing in physical activity (PA) is vital for achieving sustainable development goals. We examine PA trends in Poland using data from Eurobarometer surveys conducted in 2013, 2017, and 2022. In 2022, 64.6% of Poles did not participate in sports, and 41.8% did not engage in non-sport PA. There is a concerning trend of increasing inactivity in sports (Chi22022/2017 = 34.64; p < 0.001; Chi22017/2013 = 56.98; p < 0.001) and non-sports PA (Chi22022/2017 = 18.3, p < 0.01 and Chi22017/2013 = 16.95, p < 0.01). Participation in sport and PA is influenced by individual, inter-personal, environmental, political, and global factors. Notably, there is an upward trend in interpersonal (e.g., club membership, volunteering), environmental (e.g., PA in parks/nature, at home), and political (e.g., dissatisfaction with local government actions) factors. Government intervention is crucial and requires: (1) establishment of an institution for leadership and advocacy of PA, (2) adoption of a cross-sectoral approach for a coordinated change, and (3) increased in-vestment in monitoring systems to track the impact of interventions. These actions are essential for fostering a more active and healthier population in Poland.


Technical And Clinical Validity Of Assessing Measurable Residual Disease By Multicolor Flow Cytometry In An Unselected Acute Myeloid Leukemia Patient Cohort, Sa A Wang, Shaoying Li, Wei Wang, Jie Xu, Beenu Thakral, Shimin Hu, Chi Young Ok, Fuli Jia, Jeffrey L Jorgensen, L Jeffrey Medeiros, Farhad Ravandi, Nicholas J Short, Sanam Loghavi Jun 2025

Technical And Clinical Validity Of Assessing Measurable Residual Disease By Multicolor Flow Cytometry In An Unselected Acute Myeloid Leukemia Patient Cohort, Sa A Wang, Shaoying Li, Wei Wang, Jie Xu, Beenu Thakral, Shimin Hu, Chi Young Ok, Fuli Jia, Jeffrey L Jorgensen, L Jeffrey Medeiros, Farhad Ravandi, Nicholas J Short, Sanam Loghavi

Faculty, Staff and Student Publications

Context.—: Following the validation of a multicolor flow cytometry (MFC) assay for measurable residual disease (MRD) in acute myeloid leukemia (AML), this study examines its clinical applicability.

Objective.—: To evaluate the practicality and performance of MFC-based MRD detection in AML.

Design.—: Prospectively assessed AML MRD MFC in unselected AML patients achieving morphologic remission with follow-up studies, molecular genetics, and survival data.

Results.—: Among 379 patient bone marrow samples in this cohort, an interpretable result was obtained in 359 (95%). A total of 57 of the 359 cases (16%) were positive for MRD, and the most frequently observed immunophenotype was CD34+CD117+ …


The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo Jun 2025

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …


In Vivo Direct Lentiviral Gene Therapy Improves Disease Pathology In A Mucopolysaccharidosis Iva Murine Model, Betul Celik, Estera Rintz, Shaukat Khan, Andrés F. Leal, Fnu Nidhi, Shunji Tomatsu Jun 2025

In Vivo Direct Lentiviral Gene Therapy Improves Disease Pathology In A Mucopolysaccharidosis Iva Murine Model, Betul Celik, Estera Rintz, Shaukat Khan, Andrés F. Leal, Fnu Nidhi, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder that causes the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in bone and cartilage. This results in progressive skeletal dysplasia, with no effective treatment available. Our study hypothesized that direct lentiviral vector (LV) gene therapy could produce active enzymes from transduced cells, impacting bone and cartilage lesions in MPS IVA. We developed LVs carrying the GALNS gene under three promoters: ubiquitous (CBh), collagen type II (COL2A1), and Mac-1 integrin subunit (CD11b). At the newborn stage and 4 weeks, Galns-knockout mice received intravenous injections at different doses (5 × 109 …


Analysis Of Personality Traits, Intelligence Level And Ability To Cope With Stressful Situations And Their Impact On The Evaluation Of Judo Fights, Maciej Kostrzewa, Jan Supinski, Slawomir Kownacki, Miłosz Drozd, Anna Ścisłowska-Czarnecka, Jarosław Markowski, Jan Pilch, Alicja Markiel, Marcin Żak, Adam Maszczyk Jun 2025

Analysis Of Personality Traits, Intelligence Level And Ability To Cope With Stressful Situations And Their Impact On The Evaluation Of Judo Fights, Maciej Kostrzewa, Jan Supinski, Slawomir Kownacki, Miłosz Drozd, Anna Ścisłowska-Czarnecka, Jarosław Markowski, Jan Pilch, Alicja Markiel, Marcin Żak, Adam Maszczyk

Baltic Journal of Health and Physical Activity

Background: The aim of the study presented in this article was to conduct an analysis that would answer the research question: do personality traits such as extraversion, neuroticism, openness to experience, agreeableness, conscientiousness, intelligence level, and ability to cope with stressful situations correlate with the assessment of judo fights? Materials and Methods: Ninety individuals participated in the study, including international-class referees, national-class referees, coaches, and active judo athletes. The study used a correlational analysis approach to examine the relationships between personality traits and fight assessment criteria in judo. Results: The results indicate that in the referees' group, there is a …