Medicine and Health Sciences Commons^™

Research Highlights, Annie Valentina

Indian Journal of Research in Homoeopathy

Research Highlights

The Association Between Sampling And Survival In Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreaticoduodenectomy, Mehran Taherian, Matthew H G Katz, Laura R Prakash, Dongguang Wei, Yi Tat Tong, Zongshan Lai, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, …

A Systematic Review On The Techniques, Long-Term Outcomes, And Complications Of Partial Breast Irradiation After Breast-Conserving Surgery For Early-Stage Breast Cancer, Jing Ning, Guanghui Cheng, Ning Wu

Faculty, Staff and Student Publications

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk …

Efficacy And Safety Of Glp-1 Analog Ecnoglutide In Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dalong Zhu, Weimin Wang, Guoyu Tong, Guoqing Ma, Jianhua Ma, Jie Han, Xin Zhang, Yang Liu, Shenglian Gan, Hong Qin, Qing Zheng, Jing Ning, Zhiyi Zhu, Mengying Guo, Yue Bu, Yao Li, Catherine L Jones, Martijn Fenaux, Mohammed K Junaidi, Susan Xu, Hai Pan

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups …

Selected U.S. Government Statistical Agencies And Their Data, Bert Chapman

Libraries Faculty and Staff Presentations

Provides introductory and detailed overview of U.S. Government agencies statistics. Includes examples of how an individual U.S. law authorizes government agencies to compile statistics for particular congressional committees and the general public. Statistics cover topics such as demography, defense, foreign assistance, economic growth, criminal justice, energy, Social Security, and Medicare.

Genomic And Socioeconomic Determinants Of Racial Disparities In Breast Cancer Survival: Insights From The All Of Us Program, Nubaira Rizvi, Hui Lyu, Leah Vaidya, Xiao Cheng Wu, Lucio Miele, Qingzhao Yu

School of Public Health Faculty Publications

Background: Breast cancer outcomes are worse among Black women in the U.S. compared to White women. While extensive research has focused on risk factors contributing to breast cancer; the role of genomic elements in health disparities between these racial groups remains unclear. This study aims to identify genomic variants and socioeconomic status (SES) determinants influencing racial disparities in breast cancer survival through multiple mediation analyses. Methods: Our investigation is based on the NIH-supported All of Us (AoU) program and analyzes 7452 female participants with malignant tumors of breast, including 5073 with genomic data. A log-rank test reveals significant racial differences …

"Not A Cookie Cutter Situation": How Neurodivergent Students Experience Group Work In Their Stem Courses, Sophia Salvatore, Claudia White, Stephen Podowitz

College of Life Sciences Faculty Papers

Background: Although group work is increasingly used in STEM courses and may lead to improved academic outcomes, there is evidence that some implementations of group work may lead to unintended barriers for certain students’ learning. Despite the growing number of neurodivergent undergraduate students, there is limited research on neurodivergent students’ experiences with group work in STEM courses. To address this knowledge gap, the current research investigated the experiences of 22 neurodivergent undergraduate students with group work in STEM courses at a range of institution types and in a variety of STEM disciplines. Participants shared experiences with in-class and out-of-class group …

A Novel Model Of Autologous Tooth Transplantation For The Study Of Nerve Recruitment, Teresa E. Fowler, Doan T. Bloomquist, Caroline Glessner, Poonam Patel, Jeffrey N. James, Kathryn Bollinger, Lynnette P. Mccluskey, Ryan F. Bloomquist

School of Dentistry Faculty Publications

Background: Limited treatment options exist for damaged nerves and despite impressive advances in tissue engineering, scientists and clinicians have yet to fully replicate nerve development and recruitment. Innervation is a critical feature for normal organ function. While most organs are innervated prior to birth, a rare example of postnatal nerve recruitment occurs in the natural development of secondary teeth during adolescence. Many animals undergo postnatal shedding of deciduous teeth with development and eruption of secondary teeth, a process requiring recruitment of nerve and vasculature to each tooth pulp for viability. Here, the investigators created a novel model for the study …

Manganese Sulfanyl Porphyrazine–Mwcnt Nanohybrid Electrode Material As A Catalyst For H2o2 And Glucose Biosensors, Michal Falkowski, Amanda Leda, Mina Hassani, Michal Wicinski, Dariusz T. Mlynarczyk, Nejat Düzgüneş, Michal P. Marszall, Grzegorz Milczarek, Jaroslaw Piskorz, Tomasz Rębiś

Pacific Faculty Work

The demetallation reaction of sulfanyl magnesium(II) porphyrazine with N-ethylphthalimide substituents, followed by remetallation with manganese(II) salts, yields the corresponding manganese(III) derivative (Pz3) with high efficiency. This novel manganese(III) sulfanyl porphyrazine was characterized by HPLC and analyzed using UV-Vis, MS, and FT-IR spectroscopy. Electrochemical experiments of Pz3 conducted in dichloromethane revealed electrochemical activity of the new complex due to both manganese and N-ethylphthalimide substituents redox transitions. Subsequently, Pz3 was deposited on multiwalled carbon nanotubes (MWCNTs), and this hybrid material was then applied to glassy carbon electrodes (GC). The resulting hybrid electroactive electrode material, combining manganese(III) porphyrazine with MWCNTs, showed a significant …

Utility Of Individualised Homoeopathic Medicines In Improving Social Interaction In Childhood Autism: A Prospective, Open-Label, Single Arm Study, Sreeja Kudukayil Radhakrishnan Nair, Deepthi Gilla, Mohan Narvelil Devasia

Indian Journal of Research in Homoeopathy

Background: Childhood autism is a pervasive developmental disorder. There has been an upsurge in its prevalence in past few decades. The social deficit is the most disabling symptom of autism. There is an immediate need to explore new interventions to effectively address childhood autism. Objective: The objective of the study was to assess the usefulness of individualised homoeopathic medicine in improving social interaction in childhood autism. Materials and Methods: This one-year duration study was conducted in the outpatient department of the National Homoeopathy Research Institute in Mental Health, Kottayam, Kerala. Thirty-five children fulfilling the diagnostic criteria of childhood autism (as …

Book Review On "Homeopathy For Farm And Garden", Hima Bindu Ponnam

Indian Journal of Research in Homoeopathy

Book review on "Homeopathy for Farm and Garden"

Noninvasive Multi-Cancer Detection Using Blood-Based Cell-Free Micrornas, Jason Zhang, Hallgeir Rui, Hai Hu

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of …

Molecular Architecture Of Chitin And Chitosan-Dominated Cell Walls In Zygomycetous Fungal Pathogens By Solid-State Nmr, Qinghui Cheng, Malitha C. Dickwella Widanage, Jayasubba Reddy Yarava, Ankur Ankur, Jean Paul Latgé, Ping Wang, Tuo Wang

School of Medicine Faculty Publications

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of β-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some …

Multimodal Functional Imaging And Clinical Correlates Of Pain Regions In Chronic Low-Back Pain Patients Treated With Spinal Cord Stimulation: A Pilot Study, Yazan Shamli Oghli, Arjun Ashok, Steven Glener, Isaiah Ailes, Mashaal Syed, Kichang Kang, Sara Naghizadeh Kashani, Islam Fayed, Feroze Mohamed, Kiran Talekar, Laura Krisa, Chengyuan Wu, Caio Matias, Mahdi Alizadeh

Department of Radiology Faculty Papers

OBJECTIVE: Spinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions.

METHODS: Multi-delay 3D …

Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry

Department of Biochemistry and Molecular Biology Faculty Papers

ntroduction: Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the precursor of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Pathogenic variants in GGCX, encoding γ-glutamyl carboxylase required for activation of vitamin K-dependent coagulation factors as well as matrix Gla protein (MGP) and Gla-rich protein (GRP), two inhibitors of ectopic calcification, have also been reported to cause cutaneous changes like those seen …

A Dosimetric Comparison Of Treatment Techniques For Stereotactic Body Radiotherapy For Pancreatic Patients, Kameron Lemley

Masters Projects

Stereotactic body radiotherapy (SBRT) is utilized in radiation therapy to deliver ablative radiation doses to tumor volumes while achieving high conformity and minimal dose to surrounding critical structures. This treatment technique allows for faster dose fall-off which allows tighter treatment margins. SBRT for pancreatic cancer has been investigated for its efficacy and has proven to be an effective treatment choice for neoadjuvant radiation therapy. Since pancreatic cancer is extremely aggressive with a high mortality rate, it is important to have a treatment option that can reduce cost and increase convenience for the patient while simultaneously providing a conformal treatment plan. …

Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators

Faculty, Staff and Student Publications

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …

Spatial Organization Of Adenylyl Cyclase And Its Impact On Dopamine Signaling In Neurons, Léa Ripoll, Yong Li, Carmen W Dessauer, Mark Von Zastrow

Faculty, Staff and Student Publications

The cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes …

Mtap And P16 Ihc As Markers For Cdkn2a/B Loss In Meningiomas, Hanim I Ozkizilkaya, Anjali Vinocha, Antonio Dono, Oluwaseun Basit Ogunbona, Gokce A Toruner, Phyu P Aung, Carlos Kamiya Matsuoka, Yoshua Esquenazi, Franco Demonte, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Homozygous cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss is one of the parameters that support the designation of meningiomas as Central Nervous System (CNS) WHO grade 3 tumors. Evaluation of CDKN2A/B by sequencing or Fluorescence in situ hybridization (FISH) is costly and not always readily accessible. An immunohistochemistry (IHC)-based marker for the evaluation of CDKN2A/B loss would provide faster results at a lower cost.

Methods: This retrospective study included patients diagnosed with meningioma at our institution between 2016 and 2019. Archival tumor tissue was used for analysis. MTAP immunohistochemistry (IHC) was performed at various dilutions (1:1200, 1:400, 1:200, 1:100) using …

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

Authentication Of Shallots From Brebes Using Gas Chromatography Fingerprinting Technique Combined With Chemometrics, Yana Setyani Pradina, Adelia Puteri, Gina Fauzia Rachma, Nazwa Balqis, Gerli Puspita Anggraini, Hendri Wasito

Makara Journal of Science

Shallots from Brebes, also called Bima Brebes, have a more pungent aroma compared to other varieties. Its high demand results in increased prices in the market, leading to frequent cases of fraud wherein Bima Brebes shallots are replaced with other types of shallots. This study aimed to develop an analytical method using gas chromatography–flame ionization detector (GC-FID) fingerprinting combined with chemometrics to authenticate Bima Brebes shallots. Essential oils were extracted through ultrasonic hydrodistillation, followed by organoleptic, refractive index, GC-FID fingerprinting and chemometric analysis. The yield value of the five studied shallot varieties ranged from 0.02% to 0.08% w/w. Meanwhile, the …

Prevalence Of Cardiometabolic Risk Factors In Women: Insights From The Houston Heartreach Study, Arjun R Raghuram, Matthew W Segar, Stephanie Coulter, Joseph G Rogers

The Texas Heart Institute Journal

BACKGROUND: Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening.

METHODS: Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 …

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …

Disparities In Stage At Diagnosis Among Hispanic Patients With Gastric Cancer In The United States, Antoine Jeri-Yabar, Liliana Vittini-Hernandez, Renzo Aller-Rojas, Francisco Arias-Reyes, Sirish Dharmapuri

School of Medicine Publications

Simple Summary

This study investigates racial disparities in the stage of gastric cancer at diagnosis and overall survival among different racial groups using data from the SEER database (2018–2021). The retrospective cohort study of 18,984 patients found that Hispanics are 19% more likely to be diagnosed at a later stage of gastric cancer compared to non-Hispanics. Additionally, both Hispanics and Black patients showed poorer overall survival compared to Non-Hispanic Whites. The disparities are attributed to factors such as healthcare access, insurance coverage, language barriers, and preventive health service utilization. These findings highlight the need for targeted interventions to address these …

The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko

Faculty, Staff and Students Publications

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota.

Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored …

Awareness Of, Willingness To Use, And Experiences With Pre-Exposure Prophylaxis Among Youth In Nigeria, Titilola Gbaja-Biamila, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria.

METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for …

Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN's predictive power. We applied this method to analyze a DNN's capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This …

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …