Medicine and Health Sciences Commons^™

Tyk2 Regulates Tau Levels, Phosphorylation And Aggregation In A Tauopathy Mouse Model, Jiyoen Kim, Bakhos Tadros, Yan Hong Liang, Youngdoo Kim, Cristian Lasagna-Reeves, Jun Young Sonn, Dah-Eun Chloe Chung, Bradley Hyman, David M Holtzman, Huda Yahya Zoghbi

2020-Current year OA Pubs

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau …

Inferring Allele-Specific Copy Number Aberrations And Tumor Phylogeography From Spatially Resolved Transcriptomics, Cong Ma, Metin Balaban, Jingxian Liu, Siqi Chen, Michael J Wilson, Christopher H Sun, Li Ding, Benjamin J Raphael

2020-Current year OA Pubs

Analyzing somatic evolution within a tumor over time and across space is a key challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations in a tumor, but does not directly reveal genomic aberrations. We introduce CalicoST, an algorithm to simultaneously infer allele-specific copy number aberrations (CNAs) and reconstruct spatial tumor evolution, or phylogeography, from SRT data. CalicoST identifies important classes of CNAs-including copy-neutral loss of heterozygosity and mirrored subclonal CNAs-that are invisible to total copy number analysis. Using nine patients' data from the Human Tumor Atlas Network, CalicoST achieves an average accuracy of …

Sitravatinib In Patients With Solid Tumors Selected By Molecular Alterations: Results From A Phase Ib Study, Lyudmila Bazhenova, Douglas R Adkins, Et Al.

2020-Current year OA Pubs

No abstract provided.

Pet Clinical Study Of Novel Antipsychotic Lb-102 Demonstrates Unexpectedly Prolonged Dopamine Receptor Target Engagement, Dean F Wong, Ganesh B Chand, Nicole Caito, Anna Eramo, Vincent T Grattan, Mark S Hixon, Ginger Nicol, Erin Lessie, Zachary Prensky, Hiroto Kuwabara, Lucy Tian, Ines Valenta, Thomas H Schindler, Gerhard Gründer, Andrew R Vaino

2020-Current year OA Pubs

Regulation of dopamine activity has important clinical consequences, most notably in schizophrenia. LB-102, N-methyl amisulpride, is a novel dopamine D

Volumetric Breast Density Estimation From Three-Dimensional Reconstructed Digital Breast Tomosynthesis Images Using Deep Learning, Vinayak S Ahluwalia, Nehal Doiphode, Walter C Mankowski, Eric A Cohen, Sarthak Pati, Lauren Pantalone, Spyridon Bakas, Ari Brooks, Celine M Vachon, Emily F Conant, Aimilia Gastounioti, Despina Kontos

2020-Current year OA Pubs

PURPOSE: Breast density is a widely established independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from two-dimensional (2D) images acquired using DBT and/or depend on the existence of raw DBT data, which is rarely archived by clinical centers because of storage constraints.

METHODS: We retrospectively analyzed 1,080 nonactionable three-dimensional (3D) reconstructed DBT screening examinations acquired between 2011 and 2016. Reference tissue segmentations were generated using previously validated software that uses 3D reconstructed slices …

Dysfunctional Alpha Modulation As A Mechanism Of Working Memory Impairment In Serious Mental Illness, Molly A Erickson, Megan A Boudewyn, Kurt Winsler, Charlotte Li, Deanna M Barch, Cameron S Carter, Michael J Frank, James M Gold, Angus W Macdonald 3rd, John D Ragland, Steven M Silverstein, Andrew Yonelinas, Steven J Luck

2020-Current year OA Pubs

BACKGROUND: People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on 2 potential mechanisms: poor attentional engagement should be associated with elevated levels of prestimulus alpha-band activity within the electroencephalogram (EEG), whereas impaired working memory encoding should be associated with reduced poststimulus alpha suppression.

METHODS: We collected EEG data from 68 people with schizophrenia, 43 people with bipolar disorder with a history of psychosis, 53 people with major depressive disorder, and 90 healthy comparison subjects while they completed a spatial working memory task. We quantified attention lapsing, memory precision, and …

Radiation Oncology Opinions And Practice On Cardiotoxicity In Lung Cancer: A Cross-Sectional Study By The International Cardio-Oncology Society, G M Walls, J D Mitchell, A R Lyon, M Harbinson, G G Hanna

2020-Current year OA Pubs

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice.

MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the …

Machine Learning-Augmented Interventions In Perioperative Care: A Systematic Review And Meta-Analysis, Divya Mehta, Xiomara T Gonzalez, Grace Huang, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: We lack evidence on the cumulative effectiveness of machine learning (ML)-driven interventions in perioperative settings. Therefore, we conducted a systematic review to appraise the evidence on the impact of ML-driven interventions on perioperative outcomes.

METHODS: Ovid MEDLINE, CINAHL, Embase, Scopus, PubMed, and ClinicalTrials.gov were searched to identify randomised controlled trials (RCTs) evaluating the effectiveness of ML-driven interventions in surgical inpatient populations. The review was registered with PROSPERO (CRD42023433163) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted for outcomes with two or more studies using a random-effects model, and vote …

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Cancer And Leukemia Group B-Southwest Oncology Group 80702 (Alliance), Justin C Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M Goldberg, Eileen M O'Reilly, Anthony F Shields, Jeffrey A Meyerhardt

2020-Current year OA Pubs

BACKGROUND: Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown.

METHODS: This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free …

Correlating Clinical Course With Baseline Subcortical Shape In Provisional Tic Disorder, Tiffanie Che, Soyoung Kim, Deanna J Greene, Ashley Heywood, Jimin Ding, Tamara Hershey, Bradley L Schlaggar, Kevin J Black, Lei Wang

2020-Current year OA Pubs

OBJECTIVE: This study examined children at the onset of tic disorder (tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the baseline shape and volume of subcortical nuclei, diagnosis, and tic symptom outcomes.

METHODS: 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder/Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic …

Emergent Microenvironments Of Nucleoli, Matthew R King, Kiersten M Ruff, Rohit V Pappu

2020-Current year OA Pubs

In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types …

Incident Cardiovascular Disease Risk Among Older Asian, Native Hawaiian And Pacific Islander Liver Cancer Survivors, Jing Wang, Yancen Pan, Chun-Pin Esther Chang, Anees Daud, Randa Tao, Mia Hashibe

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is a significant global health concern, particularly among Asian, Native Hawaiian, and Pacific Islander (ANHPI) communities that face unique health challenges. Liver cancer disproportionately affects ANHPI populations and has intricate associations with CVD risks due to shared pathophysiological mechanisms and metabolic disturbances. However, the specific CVD risk profile of ANHPI liver cancer patients remains poorly understood.

METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified and matched 1150 ANHPI and 2070 Non-Hispanic White (NHW) liver cancer patients diagnosed between 2000 and 2017. We used the Fine-Gray sub-distribution hazard model to estimate hazard ratios (HRs) …

Comparative Analysis Of Pd-L1 Expression And Tumor-Infiltrating Lymphocytes In Metaplastic Breast Carcinoma And Gynecologic Carcinosarcoma: A Single-Institution Retrospective Study, Michelle S Lin, Paloma C Monroig-Bosque, Donna M Coffey, Susan L Haley, Ekene I Okoye, Michael T Deavers, Mary R Schwartz, Suzanne M Crumley

2020-Current year OA Pubs

Metaplastic breast carcinoma (MBC) and gynecologic carcinosarcoma (GCS) are rare, clinically aggressive cancers that demonstrate epithelial components and mesenchymal or sarcomatoid components. In this study, we assessed PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in MBC and GCS. Overall, PD-L1 positivity using the SP142 clone was seen in 50 % of MBC and 51.9 % of GCS cases, with PD-L1 expression in tumor cells significantly higher in MBC cases (p = 0.034), and PD-L1 expression in immune cells similar in MBC and GCS cases. PD-L1 expression was significantly higher in epithelial components than in mesenchymal components in both MBC and GCS …

Research Priorities For Children With Hypoxic-Ischemic Encephalopathy Or Myelomeningocele: A Survey Of Parents, Renée A Shellhaas, Betsy Pilon, Judy Thibadeau, Stephanie M D Rau, John D E Barks, Ronald D Chervin

2020-Current year OA Pubs

No abstract provided.

Pathogenicity And Virulence Of Human Respiratory Syncytial Virus: Multifunctional Nonstructural Proteins Ns1 And Ns2, Trudy N Merritt, Jingjing Pei, Daisy W Leung

2020-Current year OA Pubs

Human respiratory syncytial virus (hRSV) is a major cause of lower respiratory tract infections in young children, the elderly, and immunocompromised. Despite its discovery over 60 years ago and the global impact on human health, limited effective prophylactic or therapeutic options have been available for hRSV infections. This has largely been attributed to the legacy of vaccine failure in the 1960s using a formalin-inactivated RSV , which led to enhancement of disease post exposure to hRSV infection and hampered subsequent development of vaccine candidates. Recent FDA approval of vaccines for older adults and pregnant individuals are major advancements but leaves …

Cxcr3-Cxcl11 Signaling Restricts Angiogenesis And Promotes Pericyte Recruitment, Jihui Lee, Megan E. Goeckel, Allison Levitas, Sarah Colijn, Jimann Shin, Anna Hindes, Geonyoung Mun, Zarek Burton, Bharadwaj Chintalapati, Ying Yin, Javier Abello, Lilianna Solnica-Krezel, Amber N. Stratman

2020-Current year OA Pubs

BACKGROUND: Endothelial cell (EC)-pericyte interactions are known to remodel in response to hemodynamic forces; yet there is a lack of mechanistic understanding of the signaling pathways that underlie these events. Here, we have identified a novel signaling network regulated by blood flow in ECs-the chemokine receptor CXCR3 (CXC motif chemokine receptor 3) and one of its ligands, CXCL11 (CXC motif chemokine ligand 11)-that delimits EC angiogenic potential and promotes pericyte recruitment to ECs during development.

METHODS: We investigated the role of CXCR3 on vascular development using both 2- and 3-dimensional in vitro assays, to study EC-pericyte interactions and EC behavioral …

The Brief Mind Wandering Three-Factor Scale (Bmw-3), Anna-Lena Schubert, Gidon T Frischkorn, Kathrin Sadus, Matthew S Welhaf, Michael J Kane, Jan Rummel

2020-Current year OA Pubs

In recent years, researchers from different fields have become increasingly interested in measuring individual differences in mind wandering as a psychological trait. Although there are several questionnaires that allow for an assessment of people's perceptions of their mind wandering experiences, they either define mind wandering in a very broad sense or do not sufficiently separate different aspects of mind wandering. Here, we introduce the Brief Mind Wandering Three-Factor Scale (BMW-3), a 12-item questionnaire available in German and English. The BMW-3 conceptualizes mind wandering as task-unrelated thought and measures three dimensions of mind wandering: unintentional mind wandering, intentional mind wandering, and …

Identifying Dose Constraints For The Parotid Ducts To Minimize Patient-Reported Xerostomia: Is Conventional Mean Dose Sparing Of The Parotid Glands Sufficient?, Manal Ahmidouch, Shiva K Das, Tong Zhu, Colette Shen, Lawrence B Marks, Bhishamjit S Chera, David V Fried

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The aim of this study was to identify dose constraints for the parotid ducts that limit patient-reported xerostomia and estimate whether these constraints are achieved during conventional parotid gland sparing radiation therapy (PGS-RT).

METHODS AND MATERIALS: Thirty-eight oropharyngeal squamous cell carcinoma patients were treated prospectively on trial with MRI sialography-guided parotid duct sparing radiation therapy (PDS-RT). PDS-RT explicitly minimizes dose to the parotid ducts in addition to PGS-RT. Parotid duct dose constraints were identified that distinguished patients reporting high and low rates of xerostomia. Atlas-based parotid duct contours were generated on a retrospective cohort of similar patients …

Vasa Previa In Singleton Pregnancies: Diagnosis And Clinical Management Based On An International Expert Consensus, Yinka Oyelese, Anthony Odibo, Et Al.

2020-Current year OA Pubs

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies.

OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique.

STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a …

Solid-State Nmr Compositional Analysis Of Sputum From People With Cystic Fibrosis, Kathy Duong, Evan Moss, Courtney Reichhardt

2020-Current year OA Pubs

People with the genetic disease cystic fibrosis (CF) often have chronic airway infections and produce airway secretions called sputum. A better understanding of sputum composition is desired in order to track changes in response to CF therapeutics and to improve laboratory models for the study of CF airway infections. The glycosylated protein mucin is a primary component. Along with extracellular DNA, mucin gives rise to the high viscoelasticity of sputum, which inhibits airway clearance and is thought to promote chronic airway infections in people with CF. Past studies of sputum composition identified additional biomolecular components of sputum including other proteins, …

Cannabidiol Prescribing In The United States: An Analysis Of Real-World Data, Binx Yezhe Lin, Chloe Lessard, Yifan Li, Lisa Gong, Ruth Ling, Pallawi Jyotsana, Jacob Steinle, Jacob T Borodovsky, Fábio A Nascimento, Kevin Y Xu

2020-Current year OA Pubs

BACKGROUND: Off-label prescribing of Epidiolex® (pharmaceutical cannabidiol) comes with both potential benefits and risks for patients. The aims of this study were to: (1) identify the percentage of people prescribed Epidiolex® who do not have diagnostic indications for Epidiolex® (Lennox Gastaut Syndrome [LGS], Dravet Syndrome [DS], and Tuberous Sclerosis Complex [TSC]) and (2) examine potential co-prescribing of medications that may interact with Epidiolex®.

METHOD: Using TriNetX analytics, a web-based database of de-identified electronic health records spanning >110 million people in the United States, we analyzed 4214 people receiving Epidiolex® in 2022. We computed the number of people prescribed Epidiolex® who …

A Genetically Inducible Endothelial Niche Enables Vascularization Of Human Kidney Organoids With Multilineage Maturation And Emergence Of Renin Expressing Cells, Joseph C Maggiore, Haojia Wu, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. …

Mucosal Single-Cell Profiling Of Crohn's-Like Disease Of The Pouch Reveals Unique Pathogenesis And Therapeutic Targets, Siyan Cao, Khai M Nguyen, Kaiming Ma, Xiaotang Du, Xiuli Liu, Alina Ulezko Antonova, Richard P Rood, Anas Gremida, Chien-Huan Chen, Alexandra Gutierrez, Deborah C Rubin, Martin H Gregory, Mate Gergely, Guadalupe Oliva Escudero, Katherine Huang, Natalia Jaeger, Marina Cella, Rodney D Newberry, Nicholas O Davidson, Matthew A Ciorba, Parakkal Deepak, Marco Colonna

2020-Current year OA Pubs

BACKGROUND & AIMS: The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses.

METHODS: Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

2020-Current year OA Pubs

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Review And Metabolomic Profiling Of Unsolved Case Reveals Newly Reported Autosomal Dominant Congenital Disorder Of Glycosylation, Type Iw Formerly Thought To Only Be An Autosomal Recessive Condition, Kimberly M Ezell, Yutaka Furuta, Devin Oglesbee, Eniko K Pivnick, David Rinker, Jonathan H Sheehan, Rory J Tinker, Rizwan Hamid, Joy D Cogan, Lynette Rives, Serena Neumann, Brian Corner, Mary Koziura, John A Phillips 3rd, Undiagnosed Diseases Network

2020-Current year OA Pubs

Autosomal dominant congenital disorder of glycosylation (CDG) type Iw (OMIM# 619714) is caused by a heterozygous mutation in the

Kras Mutations In Endometrial Cancers: Possible Prognostic And Treatment Implications, Karolina A Kilowski, Martin F Dietrich, Joanne Xiu, Yasmine Baca, Andrew Hinton, Sarfraz Ahmad, Thomas J Herzog, Premal Thaker, Robert W Holloway

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Patients with recurrent or metastatic endometrial cancer (EC) have poor prognoses with limited therapeutic options following immunotherapy or immunochemotherapy treatments. Inhibitors of KRAS mutations (KRAS-mut) have shown efficacy in early solid tumor studies, but data in EC are lacking. This study describes the frequency of KRAS-mut relative to other oncogenic alterations in EC to identify genomic characteristics of KRAS-mut tumors that could lead to novel therapeutic options.

METHODS: A molecular database of 7870 ECs was queried for presence of oncogenic mutations and immunotherapy biomarkers. Comparisons were performed using Fisher-Exact/ChiSquare (p-values) and adjusted for multiple tests by Benjamini-Hochberg (q) and …

Acral Fibrochondromyxoid Tumor: A Clinicopathologic And Molecular Genetic Study Of 37 Cases, Carina A Dehner, Jonathan C Baker, John S A Chrisinger, Et Al.

2020-Current year OA Pubs

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that …

Stereotactic Body Radiation Therapy For Palliative Reirradiation Of Acrometastasis In The Hand From Breast Cancer, Thomas R Mazur, H Michael Gach, Joshua P Schiff, Laura L Ochoa, Michael J Naughton, Imran Zoberi

2020-Current year OA Pubs

No abstract provided.

Molecular Imaging In Experimental Pulmonary Fibrosis Reveals That Nintedanib Unexpectedly Modulates Ccr2 Immune Cell Infiltration, Hasan Farooq, Hannah P Luehmann, Jeffrey R Koenitzer, Gyu Seong Heo, Deborah H Sultan, Devesha H Kulkarni, Sean P Gunsten, Rekha M Sashti, Tao Huang, Amanda R Keller, Kory J Lavine, Jeffrey J Atkinson, Laura M Wingler, Yongjian Liu, Steven L Brody

2020-Current year OA Pubs

BACKGROUND: Pulmonary fibrosis is a challenging clinical problem with lung pathology featuring immune cell infiltrates, fibroblast expansion, and matrix deposition. Molecular analysis of diseased lungs and preclinical models have uncovered C-C chemokine receptor type 2 (CCR2)+ monocyte egress from the bone marrow into the lung, where they acquire profibrotic activities. Current drug treatment is focused on fibroblast activity. Alternatively, therapeutic targeting and monitoring CCR2+ cells may be an effective patient management strategy.

METHODS: Inhibition of CCR2+ cells and, as a benchmark, the clinical antifibrotic agent, nintedanib, were used in mouse lung fibrosis models. Lungs were evaluated directly for CCR2+ cell …

Development Of A Deep Learning Algorithm For Paneth Cell Density Quantification For Inflammatory Bowel Disease, Liang-I Kang, Kathryn Sarullo, Jon N Marsh, Liang Lu, Pooja Khonde, Changqing Ma, Talin Haritunians, Angela Mujukian, Emebet Mengesha, Dermot P B Mcgovern, Thaddeus S Stappenbeck, S Joshua Swamidass, Ta-Chiang Liu

2020-Current year OA Pubs

BACKGROUND: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation. Our aim was to use DL to quantify PCs for use as a quantitative biomarker.

METHODS: A retrospective cohort of whole slide images (WSI) of ileal tissue samples from patients with/without inflammatory bowel disease (IBD) was used for the study. A pathologist-annotated training set …