Digital Commons Network^™

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

Efficacy And Safety Of Lotilaner Ophthalmic Solution 0.25% In Demodex Blepharitis: A Systematic Review, Stephanie P. Fabara, Thalia Fabara, Akankcha Alok, Nausheen Khuddus

HCA Healthcare Journal of Medicine

Demodex blepharitis is a chronic eyelid inflammation caused by Demodex mites, which are ubiquitous skin parasites. Lotilaner, a newly United States Food and Drug Administration (FDA)-approved drug, is an antiparasitic agent that selectively inhibits parasite-specific γ-aminobutyric acid chloride channels, inducing spastic paralysis and death of Demodex mites. It is applied as an ophthalmic solution, 0.25%, twice a day for 6 weeks, and it has a long half-life and high lipophilicity, facilitating the penetration of the drug into the eyelash follicles and meibomian glands where the mites reside. This study systematically reviewed 6 clinical trials that compared lotilaner with placebo for …

Bayesian-Weighted Mendelian Randomization Reveals Sleep Apnea Syndrome Mediates The Bmi-Chronic Pain Link, Wenbao Shi, Jing Luo, Liu Yang, Dalin Chen, Yongqin Zhang, Jun Peng, Kurt Ruetzler, Manyun Sun, Hua Jin

Faculty, Staff and Student Publications

Background: Body mass index (BMI) has a complex association with a variety of chronic pain conditions, which may be influenced by sleep apnea syndrome (SAS). However, the role of SAS within the causal pathway linking BMI to chronic pain remains unconfirmed. This study explored whether and to what extent SAS serves as a mediator between BMI and chronic pain using Bayesian-weighted Mendelian randomization (BWMR) techniques.

Methods: This study utilized genome-wide association study (GWAS) summary data for BMI (N=461,460) and SAS (N=476,853; based on ICD-10 code diagnostic registries) from the IEU OpenGWAS database, along with chronic pain GWAS data (ICD-10 code-based …

Lurasidone For Pediatric Bipolar Disorder: A Systematic Review, Alexia Koukopoulos, Claudia Calderoni, Georgios D Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Gianna Autullo, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani, Delfina Janiri

Faculty, Staff and Students Publications

Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute a useful alternative for the treatment of these patients. We focused on the use of lurasidone in children and adolescents with bipolar disorder.

Methods: On 11 June 2025, we used the following strategy on PubMed: lurasidone AND ("bipolar disorder" OR "bipolar depression" OR mania OR manic). We filtered for humans and ages 0-18 years and included …

Cars And Trucks: Driving A Paradigm Shift In Hematologic Malignancies, Christine Charek, Tia Solh

Lynchburg Journal of Medical Science

Hematologic malignancies account for a significant number of annual cancer diagnoses and deaths across the globe. Historically, the prognosis for relapsed and/or refractory disease after standard therapies, such as chemotherapy and/or radiation, was poor. Chimeric antigen receptor (CAR) T-cell therapy offers an additional treatment option. While promising, this type of immunotherapy also comes with potentially severe side effects, toxicities, and limitations. A better understanding of the development, administration, and management of patients undergoing treatment can provide the general clinician with the knowledge to assist within a multidisciplinary team to ultimately improve patient outcomes.

Effectiveness Of 5% Channa Striata Extract Gel In Wound Healing: A Double-Blind Randomized Controlled Trial, Yulia Farida Yahya, Yuli Kurniawati, Erial Bahar, Theresia Lumban Toruan, Soenarto Kartowigno, Muhammad Izazi Hari Purwoko, Tiar Marina Octyvani

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Snakehead fish (Channa striata, CS) has traditionally been used in Indonesia as a nutrient to promote wound healing. It contains protein highly similar to human protein, which may be involved in wound healing via biological pathways. We aim to determine the effectiveness of the topical 5% CS extract gel in promoting wound healing.

Methods: A double-blind, placebo-controlled randomized clinical trial was conducted from June to August 2022 at the Department of Dermatology, Venereology, and Aesthetics of Dr. Mohammad Hoesin Hospital. We allocated 32 post-skin surgery participants with grade I acute superficial wounds on the face, neck, …

Comparing Sodium Fusidate And Petrolatum For Electrosurgery-Related Wound Healing: A Double-Blind Randomized Controlled Trial, Firman Parrol, Larisa Paramitha Wibawa, Irma Bernadette Simbolon Sitohang, Siti Rizny Fitriana Saldi

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Electrosurgery is a common surgical technique used to treat skin tumors. This procedure produces necrotic skin, which might impair the wound healing process, prompting physicians to prescribe topical antibiotics to prevent infection. This study aims to analyze the efficacy of sodium fusidate ointment compared to petrolatum for wound healing after electrosurgery.

Methods: We conducted a double-blind, randomized, controlled study with a within-person design. The inclusion criteria were adult subjects with seborrheic keratosis or acrochordon with a size of 4 mm to 10 mm on the face and neck, with a minimum of 2 lesions. Electrodessication was performed on the …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty, Staff and Student Publications

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …

Macular Thinning And Microvasculature Abnormalities In Children With Sickle Cell Disease: A Longitudinal Analysis, Sally S. Ong, Ann Nampomba, Sara Rahman, Loka Thangamathesvaran, Grace Reilly, Jianqiao Ma, Jay Vaidya, Sophie Lanzkron, Adrienne W. Scott

Cardeza Foundation for Hematologic Research

PURPOSE: To assess longitudinal changes in retinal thickness and vessel density (VD) in pediatric sickle cell disease (SCD).

DESIGN: A prospective cohort study.

PARTICIPANTS: Children (< 18 years old) with HbSS and HbS variant (HbSC and HbS thalassemia) genotypes were enrolled from a university-based retina subspecialty clinic from 2017 to 2019 and followed for ≥2 years.

METHODS: Participants received 3 × 3 and 6 × 6 mm OCT and OCT angiography scans at baseline and at each follow-up visit.

MAIN OUTCOME MEASURES: Retinal thickness, superficial capillary plexus (SCP), and deep capillary plexus (DCP) VD were compared over time.

RESULTS: Children with HbSS (n = 14) and HbS variant (n = 14) genotypes with ≥1 follow-up were included in the study (total 56 eyes). For HbSS, rates of retinal thinning per …

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 …

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 …

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 …

Protocol For Assessing Mobilization Of Peritoneal B Cells To The Pre-Metastatic Omentum In An Orthotopic Mouse Model Of Ovarian Cancer, Wonjae Lee, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is a visceral adipose tissue that undergoes dynamic immunological changes prior to and following metastasis. Here, we present a protocol for assessing the mobilization of peritoneal B cells to the pre-metastatic omentum in a mouse ovarian cancer model. We describe steps for isolation and adoptive transfer of peritoneal donor B cells and their detection in the omentum of recipient mice. This protocol could be utilized to study the mobilization of peritoneal B cells to the omentum in other pathological contexts. For complete details on the use and execution of this protocol, please refer to Lee et al.

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.

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 …

Abdominal Tuberculosis In Children, Melike Emiroglu, Gulsum Alkan, Meltem Kiymaz, Sadiye Kubra Tuter Oz, Hatice Turk Dagi, Mehmet Öztürk, Zeliha Esin Çelik

Journal of Pediatric Infectious Diseases

Objective: To provide an insight into the presentation, diagnosis and management of gastrointestinal tuberculosis in children.

Methods: We reviewed the medical records of children who were diagnosed with gastrointestinal tuberculosis, between October 2013 and October 2023. The analysis was performed using descriptive statistics.

Results: During the study period, 11 of 76 tuberculosis pediatric patients (14.5%) were diagnosed with gastrointestinal tuberculosis. Six of 11 patients (54.5%) were female. The median age of the patients was 60 months (51-205 months). Eight of 11 patients had intra-abdominal lymph node involvement, 3 of 11 patients had intestinal tuberculosis and 2 of 11 patients had …

Early Recurrent Midgut Volvulus Post Ladd's Procedure In A Newborn: A Case Report, Nicole Clarke, Joanna Sajdlowska, John Paul Bustamante, Nishith Bhattacharyya

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Ladd's procedure is the standard surgical intervention for intestinal malrotation. Although generally curative, rare cases of early postoperative complications, including adhesions or recurrent volvulus, can necessitate reoperation. We present the case of a full-term newborn girl who underwent emergent Ladd's procedure on Day 3 of life for malrotation with volvulus. She was discharged on postoperative Day 17 but returned the following day with recurrent bilious emesis. Imaging suggested partial obstruction. Exploratory laparotomy revealed recurrent volvulus with two twists at the duodenojejunal junction, which was successfully reduced. The patient recovered well and was discharged on postoperative Day 8. This case underscores …

Potential Strategies For Reducing Mortality And Morbidity In Acute Ischemic Cardiogenic Shock, Richard Smalling, James Mccarthy, Tim Henry, Ali Denktas

Journal of Shock and Hemodynamics

Cardiogenic shock is predominantly caused by acute ischemic myocardial injury. Despite advancements in reperfusion strategies, outcomes remain poor, with the duration of ischemia before reperfusion playing a crucial role in the development of irreversible damage. This review synthesizes insights from animal models and human studies, highlighting the limited myocardial salvage beyond 90 minutes of ischemia. In light of the high mortality rates associated with cardiogenic shock, this review proposes re-evaluating pre-hospital fibrinolysis, exploring left ventricular unloading strategies before reperfusion, and assessing the potential role of endothelin antagonists. These approaches aim to improve outcomes in this high-risk population.

Integrating Endocannabinoid Signaling, Cck Interneurons, And Hippocampal Circuit Dynamics In Behaving Animals, Shreya Malhotra, Florian Donneger, Jordan S Farrell, Barna Dudok, Attila Losonczy, Ivan Soltesz

Faculty, Staff and Students Publications

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in …

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 …

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 …

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 × 10^{9 …}

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 …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Management And Optimization Of Chronic Renal Insufficiency In The Setting Of Kidney Cancer A Systematic Review, Jessica K. Cobb, Hiroko Miyagi, Jad Chahoud, Claude Bassil, Philippe E. Spiess

Division of Internal Medicine Faculty Papers & Presentations

PURPOSE: There is a bidirectional relationship between chronic kidney disease and the incidence of renal cell carcinoma. Despite the frequency of patients with both chronic kidney disease and renal cell carcinoma, there are limited systematic reviews detailing the nuanced treatment. This review provides comprehensive insights for clinicians for managing chronic kidney disease, and renal cell carcinoma. Methods and Methods: We reviewed published literature that examined either chronic kidney disease and renal cell carcinoma or an indirect contributor of both.

RESULTS: We compare and contrast renal cell carcinoma treatment with partial and radical nephrectomies, ablative techniques, and radiation and their impact …

Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg

Dartmouth College Ph.D Dissertations

The development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.

A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose …

Type I Interferon Protects Against Bone Loss In Periodontitis By Mitigating An Interleukin (Il)-17-Neutrophil Axis, Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang

Faculty, Staff and Student Publications

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid …

Virus Against Cancer: Paradigm-Shifting Biological Concepts, Dong Ho Shin, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Purpose of review: Virotherapy has emerged as a promising approach to cancer treatment. Over the past two decades, early-phase clinical trials have demonstrated the safety and promising efficacy of virotherapy in subsets of cancer patients. However, a significant knowledge gap needs to be filled to propel the field further and achieve substantial anti-cancer benefits for more than the current 10-20% of treated patients. This article reviews the most relevant current challenges in cancer virotherapy.

Recent findings: Recent clinical observations suggest that patients who respond to virotherapy experience a shift in their immune response from an initial or concomitant response against …

Enhancing Neuronal Viability: The Protective Role Of 10% Human Cerebrospinal Fluid In Primary Neuronal Cultures, Vineet Arora, Alicia Bernhardt, Alessandro Naopli, Mijail Serruya

Farber Institute for Neuroscience Faculty Papers

Human cerebrospinal fluid (hCSF) is a physiologically rich medium containing neurotrophic factors, signaling molecules, and essential metabolites that support neuronal development, survival, and function. While its neuroprotective properties have been demonstrated in organotypic brain slices and human iPSC-derived models, its application in primary rodent cortical neuron cultures-a foundational system for studying synaptic development and neurodegeneration-remains underexplored. In this study, we systematically evaluated the effects of hCSF supplementation on neuronal viability in primary cortical cultures derived from embryonic day 18 (E18) rat embryos. To determine the optimal concentration, we tested a range of media:hCSF ratios and identified 90:10 (i.e., 10% hCSF) …