Medical Specialties Commons^™

Hunger Extends Lifespan By Modulating Histone Proteins, Hailan Liu, Hongjie Li, Yong Xu

Faculty, Staff and Students Publications

No abstract provided.

Publisher Correction: A Weakly Structured Stem For Human Origins In Africa, Aaron P Ragsdale, Timothy D Weaver, Elizabeth G Atkinson, Eileen G Hoal, Marlo Möller, Brenna M Henn, Simon Gravel

Faculty, Staff and Students Publications

No abstract provided.

Real-Time, Deep-Learning Aided Lensless Microscope, Jimin Wu, Vivek Boominathan, Ashok Veeraraghavan, Jacob T Robinson

Faculty, Staff and Students Publications

Traditional miniaturized fluorescence microscopes are critical tools for modern biology. Invariably, they struggle to simultaneously image with a high spatial resolution and a large field of view (FOV). Lensless microscopes offer a solution to this limitation. However, real-time visualization of samples is not possible with lensless imaging, as image reconstruction can take minutes to complete. This poses a challenge for usability, as real-time visualization is a crucial feature that assists users in identifying and locating the imaging target. The issue is particularly pronounced in lensless microscopes that operate at close imaging distances. Imaging at close distances requires shift-varying deconvolution to …

Retrospective Review Of 181 Patients With Pathologic Vertebral Compression Fractures, Tristen N Taylor, Callie S Bridges, Lauren E Pupa, Beatrice A Morrow, Brian G Smith, Nicole I Montgomery

Faculty, Staff and Students Publications

Background: Compression fractures are often associated with lower energy trauma and may occur in the setting of abnormal bone health associated with genetic disorders and endocrine disorders, neoplastic disease, infection, and inflammatory disorders. There is no significant series in the literature describing the prevalence or etiology of pathologic pediatric compression fractures.

Methods: IRB-approved retrospective study was performed at a tertiary children's hospital from 2012-2022. Patients < 18 years old diagnosed with atraumatic vertebral compression fractures were included and reviewed for demographics, underlying diagnosis/comorbidity, presentation, mobility, deformities, imaging data, treatments, and outcomes.

Results: 181 patients (54% Male) were included with mean age 14.17 years and follow-up of 20 months. A compression fracture was the presenting symptom of an underlying diagnosis in 32% of patients, and 21% of …

Should A Negative Microsurgical Testicular Sperm Extraction Be Repeated Routinely?, Raevti Bole, Scott D Lundy, Sarah Vij, Larry I Lipshultz, John P Lindsey, Juan R Torres-Anguiano, Michael L Eisenberg

Faculty, Staff and Students Publications

No abstract provided.

Outcomes Of Aortic Root Replacement In Patients With Marfan Syndrome: The Role Of Valve-Sparing And Valve-Replacing Approaches, Joseph S Coselli, Irina V Volguina, Lynna Nguyen, Susan Y Green, Scott A Lemaire, Marc R Moon

Faculty, Staff and Students Publications

BACKGROUND: Marfan syndrome (MFS) is a heritable thoracic aortic disease with pervasive cardiovascular effects, including commonly, a dilated aortic root. Traditionally, the root is replaced using a mechanical composite valve graft (CVG); however, this valve-replacing (VR) approach necessitates a lifelong regimen of anticoagulation with a potential for late bleeding complications. In time, valve-sparing (VS) approaches were developed. Today, several options for aortic root replacement (ARR) exist; each has advantages and disadvantages that helps inform choice. The Aortic Valve Operative Outcomes in Marfan Patients (AVOMP) is a multi-center international registry to analyze clinical outcomes of ARR in MFS patients using either …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, Jiayi M Sun, Wing-Yuk Chow, Gufeng Xu, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

Association Of Delirium And Depression With Respiratory And Outcome Measures In Covid-19 Inpatients, Alessio Simonetti, Cristina Pais, Vezio Savoia, Maria Camilla Cipriani, Matteo Tosato, Delfina Janiri, Evelina Bernardi, Ottavia Marianna Ferrara, Stella Margoni, Georgios D Kotzalidis, Daniela Chieffo, Massimo Fantoni, Rosa Liperoti, Francesco Landi, Roberto Bernabei, Gabriele Sani

Faculty, Staff and Students Publications

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the …

Addressing Wounded Healers’ Burnout And Moral Distress: Starts And Ends With Integrity, Tessy A Thomas, Frank Daniel Davis, Satid Thammasitboon

Faculty, Staff and Students Publications

No abstract provided.

Nanoparticle-Mediated Therapy With Mir-198 Sensitizes Pancreatic Cancer To Gemcitabine Treatment Through Downregulation Of Vcp-Mediated Autophagy, Christian Marin-Muller, Dali Li, Jian-Ming Lü, Zhengdong Liang, Osvaldo Vega-Martínez, Sue E Crawford, Mary K Estes, William E Fisher, Changyi Chen, Qizhi Yao

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) remains an extremely aggressive disease characterized by rapidly acquired multi-drug resistance, including to first-line chemotherapeutic agent gemcitabine. Autophagy is a process that is often exploited by cancer and is one of several intrinsic factors associated with resistance to gemcitabine. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of factors including Valosin-containing protein (VCP). VCP has been reported to play an important role in autophagic flux. In this study, we investigated whether the repression of VCP through miR-198 administration disrupts the autophagy process and sensitizes PDAC cells to gemcitabine …

Pharmaco-Proteogenomic Characterization Of Liver Cancer Organoids For Precision Oncology, Shuyi Ji, Li Feng, Zile Fu, Gaohua Wu, Yingcheng Wu, Youpei Lin, Dayun Lu, Yuanli Song, Peng Cui, Zijian Yang, Chen Sang, Guohe Song, Shangli Cai, Yuanchuang Li, Hanqing Lin, Shu Zhang, Xiaoying Wang, Shuangjian Qiu, Xiaoming Zhang, Guoqiang Hua, Junqiang Li, Jian Zhou, Zhi Dai, Xiangdong Wang, Li Ding, Pei Wang, Daming Gao, Bing Zhang, Henry Rodriguez, Jia Fan, Hans Clevers, Hu Zhou, Yidi Sun, Qiang Gao

Faculty, Staff and Students Publications

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific …

When Phased Without Water: Biophysics Of Cellular Desiccation, From Biomolecules To Condensates, Paulette Sofia Romero-Perez, Yanniv Dorone, Eduardo Flores, Shahar Sukenik, Steven Boeynaems

Faculty, Staff and Students Publications

The molecular machinery that enables life has evolved in water, yet many of the organisms around us are able to survive even extreme desiccation. Especially remarkable are single-cell and sedentary organisms that rely on specialized biomolecular machinery to survive in environments that are routinely subjected to a near-complete lack of water. In this review, we zoom in on the molecular level of what is happening in the cellular environment under water stress. We cover the various mechanisms by which biochemical components of the cell can dysfunction in dehydrated cells and detail the different strategies that organisms have evolved to eliminate …

Enabling Endpoint Development For Interventional Clinical Trials In Individuals With Angelman Syndrome: A Prospective, Longitudinal, Observational Clinical Study (Freesias), Jorrit Tjeertes, Carlos A Bacino, Terry Jo Bichell, Lynne M Bird, Mariana Bustamante, Rebecca Crean, Shafali Jeste, Robert W Komorowski, Michelle L Krishnan, Meghan T Miller, David Nobbs, Cesar Ochoa-Lubinoff, Kimberly A Parkerson, Alexander Rotenberg, Anjali Sadhwani, Mark D Shen, Lisa Squassante, Wen-Hann Tan, Brenda Vincenzi, Anne C Wheeler, Joerg F Hipp, Elizabeth Berry-Kravis

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms.

METHODS: Fifty-five individuals with AS (aged < 5 years: n = 16, 5-12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1-12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits.

RESULTS: The participants achieved high completion rates for the clinical outcome assessments (adherence: 89-100% [Clinic Visit 1]; 76-91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health …

Alemtuzumab And Cxcl9 Levels Predict Likelihood Of Sustained Engraftment After Reduced-Intensity Conditioning Hct, Ashley V Geerlinks, Brooks Scull, Christa Krupski, Ryan Fleischmann, Michael A Pulsipher, Mary Eapen, James A Connelly, Catherine M Bollard, Sung-Yun Pai, Christine N Duncan, Leslie S Kean, K Scott Baker, Lauri M Burroughs, Jeffrey R Andolina, Shalini Shenoy, Philip Roehrs, Rabi Hanna, Julie-An Talano, Kirk R Schultz, Elizabeth O Stenger, Howard Lin, Adi Zoref-Lorenz, Kenneth L Mcclain, Michael B Jordan, Tsz-Kwong Man, Carl E Allen, Rebecca A Marsh

Faculty, Staff and Students Publications

Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism < 5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell–replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day …

Recombinant Adamts-13 Improves Survival Of Mice Subjected To Endotoxemia, Daniel Gao, Zhou Zhou, Ruidong Ma, Huaizhu Wu, Trung Nguyen, Li Liu, Jingfei Dong

Faculty, Staff and Students Publications

When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and aggregating platelets. These ULVWF multimers can accumulate in the circulation and on the inflamed endothelium because they are insufficiently cleaved by the metalloprotease ADAMTS-13, which becomes moderately deficient under conditions of systemic inflammation. This moderate ADAMTS-13 deficiency may lead to thrombotic complications that contribute to ischemic tissue injury and organ failure that are associated with severe infections. To test this hypothesis, we investigated whether recombinant ADAMTS-13 improves the pathological course of endotoxemia in lipopolysaccharide (LPS)-treated mice. C57BL/J6 mice received a …

Correlative Cryo-Fib And Cryo-Et Of Dendritic Spines And Synaptic Connections, Erik D Anderson, Christopher A Cronkite, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

No abstract provided.

Comparison Of Dna Vaccines With As03 As An Adjuvant And An Mrna Vaccine Against Sars-Cov-2, Praveen Neeli, Dafei Chai, Xu Wang, Navid Sobhani, George Udeani, Yong Li

Faculty, Staff and Students Publications

Emerging variants of SARS-CoV-2 call for frequent changes in vaccine antigens. Nucleic acid-based vaccination strategies are superior as the coding sequences can be easily altered with little impact on downstream production. mRNA vaccines, including variant-specific boosters, are approved for SARS-CoV-2. Here, we tested the efficacy of DNA vaccines against the SARS-CoV-2 Spike aided by the AddaS03 adjuvant using electroporation and compared their immunogenicity with an approved mRNA vaccine (mRNA-1273). DNA vaccination elicited robust humoral and cellular immune responses in C57BL/6 mice with Spike-specific antibody neutralization and T cells produced from 20 μg DNA vaccines similar to that from 0.5 μg …

Memory Rescue And Learning In Synaptic Impaired Neuronal Circuits, Kwan Tung Li, Daoyun Ji, Changsong Zhou

Faculty, Staff and Students Publications

Neuronal impairment is a characteristic of Alzheimer's disease (AD), but its effect on neural activity dynamics underlying memory deficits is unclear. Here, we studied the effects of synaptic impairment on neural activities associated with memory recall, memory rescue, and learning a new memory, in an integrate-and-fire neuronal network. Our results showed that reducing connectivity decreases the neuronal synchronization of memory neurons and impairs memory recall performance. Although, slow-gamma stimulation rescued memory recall and slow-gamma oscillations, the rescue caused a side effect of activating mixed memories. During the learning of a new memory, reducing connectivity caused impairment in storing the new …

Satisfaction With Participation In The First Steps Behavioral Intervention: Experiences Of Parents Of Young Children With Newly Diagnosed Type 1 Diabetes, Marissa N Baudino, Hailey Inverso, Christine Wang, Carrie Tully, Wendy Levy, Lauren Clary, Katherine A Gallagher, Maureen Monaghan, Randi Streisand, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: Parents of young children with new-onset type 1 diabetes (T1D) often experience significant distress and struggle with T1D management during a challenging developmental stage. The First STEPS (Study of Type 1 in Early childhood and Parenting Support) trial evaluated a stepped-care behavioral intervention comprising increasingly intensive intervention steps (peer parent coach, cognitive-behavioral counseling, consultations with diabetes educator and psychologist) based on need. The intervention improved parental depressive symptoms compared to usual care. Subsequently, we examined parent satisfaction with the intervention to guide potential implementation and refinement for future trials.

METHODS: Participants were 157 parents of young children newly diagnosed …

Dynamic Mapping Of Proteome Trafficking Within And Between Living Cells By Transitid, Wei Qin, Joleen S Cheah, Charles Xu, James Messing, Brian D Freibaum, Steven Boeynaems, J Paul Taylor, Namrata D Udeshi, Steven A Carr, Alice Y Ting

Faculty, Staff and Students Publications

The ability to map trafficking for thousands of endogenous proteins at once in living cells would reveal biology currently invisible to both microscopy and mass spectrometry. Here, we report TransitID, a method for unbiased mapping of endogenous proteome trafficking with nanometer spatial resolution in living cells. Two proximity labeling (PL) enzymes, TurboID and APEX, are targeted to source and destination compartments, and PL with each enzyme is performed in tandem via sequential addition of their small-molecule substrates. Mass spectrometry identifies the proteins tagged by both enzymes. Using TransitID, we mapped proteome trafficking between cytosol and mitochondria, cytosol and nucleus, and …

Competencies For Psychology Practice In Pediatric Palliative Care, Amanda L Thompson, Megan R Schaefer, Sarah R Mccarthy, Aimee K Hildenbrand, Melissa K Cousino, Meghan L Marsac, Jill Majeski, Karen Wohlheiter, Rachel A Kentor

Faculty, Staff and Students Publications

Objective: Pediatric psychologists have unique expertise to contribute to the care of youth with serious illnesses yet are not routinely integrated into pediatric palliative care (PPC) teams. To better define the role and unique skillset of psychologists practicing in PPC, support their systematic inclusion as part of PPC teams, and advance trainee knowledge of PPC principles and skills, the PPC Psychology Working Group sought to develop core competencies for psychologists in this subspecialty.

Methods: A Working Group of pediatric psychologists with expertise in PPC met monthly to review literature and existing competencies in pediatrics, pediatric and subspecialty psychology, adult palliative …

Βii-Spectrin Is Required For Synaptic Positioning During Retinal Development, Debalina Goswami-Sewell, Caitlin Bagnetto, Cesiah C Gomez, Joseph T Anderson, Akash Maheshwari, Elizabeth Zuniga-Sanchez

Faculty, Staff and Students Publications

Neural circuit assembly is a multistep process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here, we uncovered a new role for the cytoskeletal protein βII-spectrin in properly positioning presynaptic and postsynaptic neurons to the developing synaptic layer. Loss of βII-spectrin …

Dual Antiplatelet Therapy: A Concise Review For Clinicians, Hafeez Ul Hassan Virk, Johao Escobar, Mario Rodriguez, Eric R Bates, Umair Khalid, Hani Jneid, Yochai Birnbaum, Glenn N Levine, Sidney C Smith, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular …

Comparison Of Left Bundle Branch Area Pacing And Biventricular Pacing In Candidates For Resynchronization Therapy, Pugazhendhi Vijayaraman, Parikshit S Sharma, Óscar Cano, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Francesco Zanon, Marek Jastrzebski, Jiangang Zou, Mihail G Chelu, Kevin Vernooy, Zachary I Whinnett, Girish M Nair, Manuel Molina-Lerma, Karol Curila, Dipen Zalavadia, Abdul Haseeb, Cicely Dye, Sharath C Vipparthy, Ryan Brunetti, Pawel Moskal, Alexandra Ross, Antonius Van Stipdonk, Jerin George, Yusuf K Qadeer, Mishal Mumtaz, Jeffrey Kolominsky, Syeda A Zahra, Mehrdad Golian, Lina Marcantoni, Faiz A Subzposh, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP.

Objectives: The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT.

Methods: This observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to …

Many Pediatric Patients With Gastroparesis Do Not Receive Dietary Education, Debra Eseonu, Deepa Dongarwar, Hamisu Salihu, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Gastroparesis is delayed gastric emptying in the absence of obstruction; dietary modifications are first-line treatment. However, we do not know the factors related to provision of dietary recommendations.

METHODS: We sought to determine how often pediatric patients with gastroparesis receive dietary education (from a gastroenterology provider vs dietitian), the recommendations given, and factors related to these outcomes. We performed a retrospective chart review of children 2- to 18-years-old managed by pediatric gastroenterology providers at our institution. Patient demographics and clinical data, dietary advice given (if any), and dietitian consultation (if any), practice location, and prokinetic use were captured. An …

Temporal Trends And Geographic Variations In Mortality Rates From Tobacco And Firearms In The United States, Sarah A Palumbo, Robert S Levine, Janet D Robishaw, Charles H Hennekens

Faculty, Staff and Students Publications

We explored temporal trends and geographic variations in United States of America (US) mortality rates from smoking and firearms from 1999 to 2019. To do so, we used the publicly available Centers for Disease Control and Prevention (CDC) Wide Ranging Online Data for Epidemiologic Research (WONDER) with Multiple Cause of Death files from 1999 to 2019. Using age-specific rates and ArcGIS Pro Advanced software for Optimized Hot Spot Analyses from Esri, we generated maps of statistically significant spatial clusters with 90-99% confidence intervals with the Getis-Ord Gi* statistic for mortality from smoking-related causes and firearms. These data show temporal trends …

Performance Of A Modified Fracture Risk Assessment Tool For Fragility Fracture Prediction Among Older Veterans Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Farah Kidwai-Khan, Melissa Skanderson, Thomas M Gill, Barbara Gulanski, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Evelyn Hsieh

Faculty, Staff and Students Publications

OBJECTIVE: Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a 'modified FRAX' identifies PAH at risk for fractures in a contemporary HIV cohort.

DESIGN: Cohort study.

METHODS: We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to …

Pediatric Phase 2 Trial Of A Wee1 Inhibitor, Adavosertib (Azd1775), And Irinotecan For Relapsed Neuroblastoma, Medulloblastoma, And Rhabdomyosarcoma, Kristina A Cole, Heba Ijaz, Lea F Surrey, Mariarita Santi, Xiaowei Liu, Charles G Minard, John M Maris, Stephan Voss, Joel M Reid, Elizabeth Fox, Brenda J Weigel

Faculty, Staff and Students Publications

BACKGROUND: Inhibition of the WEE1 kinase by adavosertib (AZD1775) potentiates replicative stress from genomic instability or chemotherapy. This study reports the pediatric solid tumor phase 2 results of the ADVL1312 trial combining irinotecan and adavosertib.

METHODS: Pediatric patients with recurrent neuroblastoma (part B), medulloblastoma/central nervous system embryonal tumors (part C), or rhabdomyosarcoma (part D) were treated with irinotecan and adavosertib orally for 5 days every 21 days. The combination was considered effective if there were at least three of 20 responses in parts B and D or six of 19 responses in part C. Tumor tissue was analyzed for alternative …

Are The Post-Covid-19 Posttraumatic Stress Disorder (Ptsd) Symptoms Justified By The Effects Of Covid-19 On Brain Structure? A Systematic Review, Georgios D Kotzalidis, Ottavia Marianna Ferrara, Stella Margoni, Valentina Ieritano, Antonio Restaino, Evelina Bernardi, Alessia Fischetti, Antonello Catinari, Laura Monti, Daniela Pia Rosaria Chieffo, Alessio Simonetti, Gabriele Sani

Faculty, Staff and Students Publications

COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer …

Molecular Dissection And Testing Of Prss37 Function Through Lc-Ms/Ms And The Generation Of A Prss37 Humanized Mouse Model, Courtney Sutton, Kaori Nozawa, Katarzyna Kent, Alexander Saltzman, Mei Leng, Sureshbabu Nagarajan, Anna Malovannaya, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The quest for a non-hormonal male contraceptive pill for men still exists. Serine protease 37 (PRSS37) is a sperm-specific protein that when ablated in mice renders them sterile. In this study we sought to examine the molecular sequelae of PRSS37 loss to better understand its molecular function, and to determine whether human PRSS37 could rescue the sterility phenotype of knockout (KO) mice, allowing for a more appropriate model for drug molecule testing. To this end, we used CRISPR-EZ to create mice lacking the entire coding region of Prss37, used pronuclear injection to create transgenic mice expressing human PRSS37, intercrossed these …