Medical Specialties Commons^™

Exposure To Light At Night And Risk Of Cancer: A Systematic Review, Meta-Analysis, And Data Synthesis, Samuel Ma, Yossef Alsabawi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Emerging interest surrounds the role of environmental factors, notably exposure to light at night (LAN), as a potential cause of cancer. The aim of this study was to conduct a systematic review and, if possible, meta-analysis of observational studies on LAN and cancer risk of multiple types.

METHODS: A systematic literature search in PubMed, Web of Science, and Embase, spanning from inception to May 2023, was conducted. Studies focusing on the association between LAN exposure and cancer risk in adult populations were included. We used random effects models to calculate pooled risk estimates (RR) and 95% confidence intervals (CI). …

N-Myc And Stat Interactor Is An Endometriosis Suppressor, Yuri Park, Xiaoming Guan, Sang Jun Han

Faculty, Staff and Students Publications

In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI …

Randomized, Double-Blind, Placebo-Controlled Study Of Anti-Mycobacterial Therapy (Rhb-104) In Active Crohn's Disease, David Y Graham, Saleh A Naser, Thomas Borody, Zbigniew Hebzda, Harry Sarles, Scott Levenson, Robert Hardi, Tomasz Arłukowicz, Petar Svorcan, Reza Fathi, Aida Bibliowicz, Patricia Anderson, Patrick Mclean, Clara Fehrmann, M Scott Harris, Shuhong Zhao, Ira N Kalfus

Faculty, Staff and Students Publications

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn’s disease. A double-blind multicenter study of adults with active Crohn’s disease, (i.e., Crohn’s Disease Activity Index [CDAI] 220–450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn’s disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, …

Vaccine Value Profile For Hookworm, Karl Philipp Puchner, Maria Elena Bottazzi, Victoria Periago, Martin Grobusch, Rick Maizels, James Mccarthy, Bruce Lee, Erika Gaspari, David Diemert, Peter Hotez

Faculty, Staff and Students Publications

Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and remains one of the leading causes of mild to severe anemia in Low and Middle Income Countries (LMICs), particularly in pregnancy and children under 5. Despite repeated large scale Preventive Chemotherapy (PC) interventions since more than 3 decades, there is broad consensus among scholars that elimination targets set in the newly launched NTD roadmap will require additional tools and interventions. Development of a vaccine could constitute a promising expansion of the existing arsenal against hookworm. Therefore, we …

The Interplay Between Gender And Duration Of Hospitalization Modulates Psychiatric Symptom Severity In Subjects With Long Covid-19, Alessio Simonetti, Antonio Restaino, Claudia Calderoni, Emanuela De Chiara, Antonio Maria D'Onofrio, Salvatore Lioniello, Giovanni Camardese, Delfina Janiri, Matteo Tosato, Francesco Landi, Gabriele Sani

Faculty, Staff and Students Publications

Long COVID-19 is characterized by ongoing symptoms or prolonged or long-term complications of SARS-CoV-2 contraction which persist beyond 4 weeks from the initial onset of symptoms. Gender and duration of hospitalization (DH) are key risk factors for developing long COVID-19 syndrome, but their impact and interplay need further study. This research involved 996 long COVID-19 patients, and we compared the levels of general psychopathology, depression, agitated depression, anxiety, and medication use between hospitalized and non-hospitalized males and females. In the hospitalized patients, multivariate regressions assessed the impact of gender, DH, and the interaction of these variables. The females had higher …

A Light-Responsive Neural Circuit Suppresses Feeding, Hailan Liu, Na Qu, Natalia Valdez Gonzalez, Marco A Palma, Huamin Chen, Jiani Xiong, Abhinav Choubey, Yongxiang Li, Xin Li, Meng Yu, Hesong Liu, Longlong Tu, Nan Zhang, Na Yin, Kristine Marie Conde, Mengjie Wang, Jonathan Carter Bean, Junying Han, Nikolas Anthony Scarcelli, Yongjie Yang, Kenji Saito, Huxing Cui, Qingchun Tong, Zheng Sun, Chunmei Wang, Xing Cai, Li Lu, Yang He, Yong Xu

Faculty, Staff and Students Publications

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition …

Hyaluronan Mediates Cold-Induced Adipose Tissue Beiging, Xi Chen, Yifan Wang, Huiqiao Li, Yanru Deng, Charlise Giang, Anying Song, Yu'e Liu, Qiong A Wang, Yi Zhu

Faculty, Staff and Students Publications

Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear …

Sutureless Valves, A "Wireless" Option For Patients With Aortic Valve Disease: Jacc State-Of-The-Art Review, Cristiano Spadaccio, Antonio Nenna, Angelo Pisani, Grzegorz Laskawski, Francesco Nappi, Marc R Moon, Fausto Biancari, Arminder S Jassar, Kevin L Greason, Malakh L Shrestha, Nikolaos Bonaros, David Rose

Faculty, Staff and Students Publications

Transcatheter technologies triggered the recent revision of the guidelines that progressively widened the indications for the treatment of aortic stenosis. On the surgical realm, a technology avoiding the need for sutures to anchor the prosthesis to the aortic annulus has been developed with the aim to reduce the duration of cardiopulmonary bypass and simplify the process of valve implantation. In addition to a transcatheter aortic valve replacement (TAVR)-like stent that exerts a radial force, these so-called "rapid deployment valves" or "sutureless valves" for aortic valve replacement also have cuffs to improve sealing and reduce the risk of paravalvular leak. Despite …

Bile Acid-Sensitive Human Norovirus Strains Are Susceptible To Sphingosine-1-Phosphate Receptor 2 Inhibition, Victoria Tenge, B Vijayalakshmi Ayyar, Khalil Ettayebi, Sue E Crawford, Nicole M Hayes, Yi-Ting Shen, Frederick H Neill, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause endemic and pandemic acute viral gastroenteritis. Previously, we reported that many HuNoV strains require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. BA was not essential for the replication of a pandemic-causing GII.4 HuNoV strain. We found the hydrophobic BA glycochenodeoxycholic acid (GCDCA) promotes the replication of the BA-dependent strain GII.3 in jejunal enteroids. Furthermore, we found that inhibition of the G-protein-coupled BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), by JTE-013, reduced GII.3 infection dose-dependently and inhibited GII.3 cellular uptake in enteroids. Herein, we sought …

Association Between Diabetes Mellitus And Total Hip Arthroplasty Outcomes: An Observational Study Using The Us National Inpatient Sample, Sumanth Chandrupatla, Kranti Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

OBJECTIVES: To investigate the association of diabetes with postoperative outcomes in patients undergoing primary total hip arthroplasty (THA).

DESIGN: Retrospective cohort study using data from the US National Inpatient Sample (NIS).

SETTING: Study cohort was hospitalisations for primary THA in the USA, identified from the 2016-2020 NIS.

PARTICIPANTS: We identified 2 467 215 adults in the 2016-2020 NIS who underwent primary THA using International Classification of Diseases, 10th Revision codes. Primary THA hospitlizations were analysed as the overall group and also stratified by the underlying primary diagnosis for THA.

OUTCOME MEASURES: Outcome measures of interest were the length of hospital …

A Trivalent Protein-Based Pan-Betacoronavirus Vaccine Elicits Cross-Neutralizing Antibodies Against A Panel Of Coronavirus Pseudoviruses, Syamala Rani Thimmiraju, Rakesh Adhikari, Jeanna R Redd, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Yi-Lin Chen, Suman Sharma, Amandeep Kaur, Nestor L Uzcategui, Shannon E Ronca, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

A Guide To Transcatheter Aortic Valve Design And Systematic Planning For A Redo-Tav (Tav-In-Tav) Procedure, Vinayak N Bapat, Miho Fukui, Syed Zaid, Atsushi Okada, Hasan Jilaihawi, Toby Rogers, Omar Khalique, João L Cavalcante, Uri Landes, Janarthanan Sathananthan, Giuseppe Tarantini, Gilbert H L Tang, Daniel J Blackman, Ole De Backer, Michael J Mack, Martin B Leon

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement (TAVR) has become more common than surgical aortic valve replacement since 2016, with over 200,000 procedures globally each year. As patients increasingly outlive their TAVR devices, managing these cases is a growing concern. Treatment options include surgical removal of the old TAVR device (transcatheter aortic valve [TAV] explant) or implantation of a new transcatheter aortic valve (redo TAV). Redo TAV is complex because of the unique designs of TAV devices; compatibility issues; and the need for individualized planning based on factors such as implant depth, shape, and coronary artery relationships. This review serves as a comprehensive …

Onecut2 Acts As A Lineage Plasticity Driver In Adenocarcinoma As Well As Neuroendocrine Variants Of Prostate Cancer, Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar, Stephen J Freedland, Edwin M Posadas, Leigh Ellis, Dolores Di Vizio, Colm Morrissey, Peter S Nelson, Lauren Brady, Ramachandran Murali, Moray J Campbell, Wei Yang, Beatrice S Knudsen, Elahe A Mostaghel, Huihui Ye, Isla P Garraway, Sungyong You, Michael R Freeman

Faculty, Staff and Students Publications

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic …

Development And Implementation Of A Digital Quality Measure Of Emergency Cancer Diagnosis, Paarth Kapadia, Andrew J Zimolzak, Divvy K Upadhyay, Saritha Korukonda, Riyaa Murugaesh Rekha, Umair Mushtaq, Usman Mir, Daniel R Murphy, Alexis Offner, Gary A Abel, Georgios Lyratzopoulos, Luke T A Mounce, Hardeep Singh

Faculty, Staff and Students Publications

PURPOSE: Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality.

METHODS: On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) …

Overcoming Challenges For Non-Us International Medical Graduates In Pediatric Infectious Diseases, Zheyi Teoh, Guliz Erdem, Cristina Tomatis-Souverbielle, Diego A Cruz-Vidal, Maria S Rueda, Roberto P Santos, Liset Olarte

Faculty, Staff and Students Publications

No abstract provided.

Gestational Diabetes As A Risk Factor For Gbs Maternal Rectovaginal Colonization: A Systematic Review And Meta-Analysis, Vicki Mercado-Evans, Jacob J Zulk, Zainab A Hameed, Kathryn A Patras

Faculty, Staff and Students Publications

BACKGROUND: Maternal rectovaginal colonization by group B Streptococcus (GBS) increases the risk of perinatal GBS disease that can lead to death or long-term neurological impairment. Factors that increase the risk of rectovaginal GBS carriage are incompletely understood resulting in missed opportunities for detecting GBS in risk-based clinical approaches. There is a lacking consensus on whether gestational diabetes mellitus (GDM) is a risk factor for rectovaginal GBS. This systematic review and meta-analysis aims to address current conflicting findings and determine whether GDM should be clinically considered as a risk factor for maternal GBS colonization.

METHODS: Peer-reviewed studies that provided GDM prevalence …

Assessing Breast Disease With Deep Learning Model Using Bimodal Bi-View Ultrasound Images And Clinical Information, Fengping Liang, Yihua Song, Xiaoping Huang, Tong Ren, Qiao Ji, Yanan Guo, Xiang Li, Yajuan Sui, Xiaohui Xie, Lanqing Han, Yuanqing Li, Yong Ren, Zuofeng Xu

Faculty, Staff and Students Publications

Breast cancer is the second leading cause of carcinoma-linked death in women. We developed a multi-modal deep-learning model (BreNet) to differentiate breast cancer from benign lesions. BreNet was constructed and trained on 10,108 images from one center and tested on 3,762 images from two centers in three steps. The diagnostic ability of BreNet was first compared with that of six radiologists; a BreNet-aided scheme was constructed to improve the diagnostic ability of the radiologists; and the diagnosis of real-world radiologists' scheme was then compared with the BreNet-aided scheme. The diagnostic performance of BreNet was superior to that of the radiologists …

Novel Mutation Leading To Splice Donor Loss In A Conserved Site Of Dmd Gene Causes Duchenne Muscular Dystrophy With Cryptorchidism, Jianhai Chen, Yangying Jia, Jie Zhong, Kun Zhang, Hongzheng Dai, Guanglin He, Fuping Li, Li Zeng, Chuanzhu Fan, Huayan Xu

Faculty, Staff and Students Publications

Background: As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants.

Methods: In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype.

Results: In …

If At First We Don't Succeed, Should We Try, Try Again?, Kriti Puri, Susan W Denfield

Faculty, Staff and Students Publications

No abstract provided.

Single-Cell Total-Rna Profiling Unveils Regulatory Hubs Of Transcription Factors, Yichi Niu, Jiayi Luo, Chenghang Zong

Faculty, Staff and Students Publications

Recent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from unspliced RNA to spliced RNA (i.e., mature RNA) to degradation. To feed this kinetic analysis, simultaneous measurement of unspliced RNA and spliced RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry primarily captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based single-cell RNA-seq method: snapTotal-seq. We benchmark this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression …

Pure Epidural Extraosseous Cavernous Hemangioma With Thoracic Myelopathy: Case Report And Review Of Literature, Jordan Guntin, Ashley Ricciardelli, Alex Flores, Jeffrey Chen, Jeffrey Treiber, Alfonso Fuentes

Faculty, Staff and Students Publications

Introduction: Pure epidural spinal cavernous hemangiomas are rare, benign vascular tumors that account for approximately 4% of all spinal epidural tumors. Due to their dumbbell shape and propensity for foraminal invasion, they are often misdiagnosed and inadequately treated. We present a case of a 58-year-old male with extra-osseous cavernous hemangioma to better aid in diagnosis and management of these lesions.

Case presentation: A 58-year-old male presented with chronic lower back pain, progressive lower extremity weakness, T10 sensory level, absent lower extremity proprioception, hyperreflexia, and an episode of bowel incontinence. Imaging demonstrated T7-T10 homogenous dorsal epidural mass causing cord signal change. …

Systemic Interindividual Dna Methylation Variants In Cattle Share Major Hallmarks With Those In Humans, Wen-Jou Chang, Maria S Baker, Eleonora Laritsky, Chathura J Gunasekara, Uditha Maduranga, Justine C Galliou, Joseph W Mcfadden, Jessica R Waltemyer, Bruce Berggren-Thomas, Brianna N Tate, Hanxue Zhang, Benjamin D Rosen, Curtis P Van Tassell, George E Liu, Cristian Coarfa, Yi Athena Ren, Robert A Waterland

Faculty, Staff and Students Publications

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle.

RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, …

Transcriptomic Analysis Reveals The Anti-Cancer Effect Of Gestational Mesenchymal Stem Cell Secretome, Salvatore Vaiasicca, Gianmarco Melone, David W James, Marcos Quintela, Jing Xiao, Seydou Yao, Richard H Finnell, Robert S Conlan, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties …

Setd3 Is A Mechanosensitive Enzyme That Methylates Actin On His73 To Regulate Mitochondrial Dynamics And Function, Vaibhav Deshmukh, James F Martin

Faculty, Staff and Students Publications

Mitochondria, which act as sensors of metabolic homeostasis and metabolite signaling, form a dynamic intracellular network that continuously changes shape, size and localization to respond to localized cellular energy demands. Mitochondrial dynamics and function depend on interactions with the F-actin cytoskeleton that are poorly understood. Here, we show that SET domain protein 3 (SETD3), a recently described actin histidine methyltransferase, directly methylates actin at histidine-73 and enhances F-actin polymerization on mitochondria. SETD3 is a mechano-sensitive enzyme that is localized on the outer mitochondrial membrane and promotes actin polymerization around mitochondria. SETD3 loss of function leads to diminished F-actin around mitochondria …

Associations Of Ambulatory Blood Pressure Measurements With High-Sensitivity Troponin And Natriuretic Peptide Levels In Sprint, Nikit Venishetty, Jarett D Berry, James A De Lemos, Elaine Wu, Minjae Lee, Paul E Drawz, Vijay Nambi, Christie M Ballantyne, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Simon B Ascher

Faculty, Staff and Students Publications

Background: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD.

Methods: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels.

Results: The mean age was 69 ± 12 …

Langerhans Cell Histiocytosis: Nacho Update On Progress, Chaos, And Opportunity On The Path To Rational Cures, Kevin Bielamowicz, Peter Dimitrion, Oussama Abla, Simon Bomken, Patrick Campbell, Matthew Collin, Barbara Degar, Eli L Diamond, Olive S Eckstein, Nader El-Mallawany, Mark Fluchel, Gaurav Goyal, Michael M Henry, Michelle Hermiston, Michael Hogarty, Michael Jeng, Rima Jubran, Joseph Lubega, Ashish Kumar, Stephan Ladisch, Kenneth L Mcclain, Miriam Merad, Qing-Sheng Mi, D Williams Parsons, Erin Peckham-Gregory, Jennifer Picarsic, Zachary D Prudowsky, Barrett J Rollins, Peter H Shaw, Birte Wistinghausen, Carlos Rodriguez-Galindo, Carl E Allen, North American Consortium For Histiocytosis

Faculty, Staff and Students Publications

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus …

Tractography-Based Modeling Explains Treatment Outcomes In Patients Undergoing Deep Brain Stimulation For Obsessive-Compulsive Disorder, Ron Gadot, Ningfei Li, Ben Shofty, Michelle Avendano-Ortega, Sarah Mckay, Kelly R Bijanki, Meghan E Robinson, Garrett Banks, Nicole Provenza, Eric A Storch, Wayne K Goodman, Andreas Horn, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target.

METHODS: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract.

RESULTS: Rank …

Beta Activity In Human Anterior Cingulate Cortex Mediates Reward Biases, Jiayang Xiao, Joshua A Adkinson, John Myers, Anusha B Allawala, Raissa K Mathura, Victoria Pirtle, Ricardo Najera, Nicole R Provenza, Eleonora Bartoli, Andrew J Watrous, Denise Oswalt, Ron Gadot, Adrish Anand, Ben Shofty, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Xaq Pitkow, Kelly R Bijanki, Benjamin Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for …

27-Hydroxycholesterol Acts On Estrogen Receptor Α Expressed By Pomc Neurons In The Arcuate Nucleus To Modulate Feeding Behavior, Hui Ye, Xiaohua Yang, Bing Feng, Pei Luo, Valeria C Torres Irizarry, Leslie Carrillo-Sáenz, Meng Yu, Yongjie Yang, Benjamin P Eappen, Marcos David Munoz, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Penghua Lai, Xinyue Qi, Yuliang Zhou, Maya Kota, Devin Dixit, Madeline Mun, Chong Wee Liew, Yuwei Jiang, Chunmei Wang, Yanlin He, Pingwen Xu

Faculty, Staff and Students Publications

Oxysterols are metabolites of cholesterol that regulate cholesterol homeostasis. Among these, the most abundant oxysterol is 27-hydroxycholesterol (27HC), which can cross the blood-brain barrier. Because 27HC functions as an endogenous selective estrogen receptor modulator, we hypothesize that 27HC binds to the estrogen receptor α (ERα) in the brain to regulate energy balance. Supporting this view, we found that delivering 27HC to the brain reduced food intake and activated proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (POMCARH) in an ERα-dependent manner. In addition, we observed that inhibiting brain ERα, deleting ERα in POMC neurons, or chemogenetic inhibition of …

Monoallelic De Novo Ajap1 Loss-Of-Function Variants Disrupt Trans-Synaptic Control Of Neurotransmitter Release, Simon Früh, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaite, Li-Yuan Chen, Diego Fernandez-Fernandez, Pascal D Rem, Daniel Ulrich, Jochen Schwenk, Ziyang Chen, Elodie Le Monnier, Thorsten Fritzius, Sabrina M Innocenti, Valérie Besseyrias, Luca Trovò, Michal Stawarski, Emanuela Argilli, Elliott H Sherr, Bregje Van Bon, Erik-Jan Kamsteeg, Maria Iascone, Alba Pilotta, Maria R Cutrì, Mahshid S Azamian, Andrés Hernández-García, Seema R Lalani, Jill A Rosenfeld, Xiaonan Zhao, Tiphanie P Vogel, Herda Ona, Daryl A Scott, Peter Scheiffele, Kristian Strømgaard, Mehdi Tafti, Martin Gassmann, Bernd Fakler, Ryuichi Shigemoto, Bernhard Bettler

Faculty, Staff and Students Publications

Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed …