Digital Commons Network^™

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.

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 …

Pedicle Screw Placement In The Cervical Vertebrae Using Augmented Reality-Head Mounted Displays: A Cadaveric Proof-Of-Concept Study, Miguel A Ruiz-Cardozo, Karma Barot, Samuel Brehm, Tim Bui, Karan Joseph, Michael Ryan Kann, Gabriel Trevino, Michael Olufawo, Som Singh, Alexander T Yahanda, Alexander Perdomo-Pantoja, Magalie Cadieux, Camilo A Molina, Et Al.

2020-Current year OA Pubs

BACKGROUND: The accurate and safe positioning of cervical pedicle screws is crucial. While augmented reality (AR) use in spine surgery has previously demonstrated clinical utility in the thoracolumbar spine, its technical feasibility in the cervical spine remains less explored.

PURPOSE: The objective of this study was to assess the precision and safety of AR-assisted pedicle screw placement in the cervical spine.

STUDY DESIGN: In this experimental study, 5 cadaveric cervical spine models were instrumented from C3 to C7 by 5 different spine surgeons. The navigation accuracy and clinical screw accuracy were evaluated.

METHODS: Postprocedural CT scans were evaluated for clinical …

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 …

Three Techniques For 360-Degree Gonioscopy-Assisted Transluminal Trabeculotomy With Itrack Advance, Sean Smith, Jessie Wang, Shivani Kamat, Arsham Sheybani, Ian Patterson, Mary Qiu

2020-Current year OA Pubs

PURPOSE: 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) is a safe and effective angle-based intervention to lower IOP. Use of the iTrack Advance allows the surgeon to efficiently advance the microcatheter in one continuous motion with a slider, an improvement upon previous techniques in which microcatheters or sutures which had to be manually threaded through Schlemm's canal with microforceps. This report demonstrates three variations in surgical technique for successful 360-degree GATT using the iTrack Advance.

OBSERVATIONS: The first technique requires retrieval of the tip of the microcatheter and requires an assistant to hold the gonioprism. The second method also requires retrieval of …

Optimizing Topical Drop Efficacy With Proper Eyelid Positioning, Yu Xia, Nathaniel A Blecher, Philip L Custer, Erin G Sieck

2020-Current year OA Pubs

PURPOSE: To report the observation that the efficacy of topical glaucoma treatment improved after surgical correction of ectropion in a 71-year-old male with a known history of glaucoma.

OBSERVATIONS: The patient initially presented for tearing and lid malposition and was found to have bilateral elevated intraocular pressures (IOP) in addition to bilateral lower eyelid ectropion. IOP control was initially prioritized over ectropion repair, with IOP remaining elevated despite topical glaucoma treatment and selective laser trabeculoplasty. Sequential unilateral ectropion repair was then carried out, with topical glaucoma treatment resumed after the first repair. It was observed that the IOP improved with …

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 …

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 …

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 …

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 …

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 …

General Versus Interventional Gastroenterologists: A Comparative Analysis Of Follow-Up Outcomes After Endoscopic Mucosal Resection Of Colorectal Polyps, Mahmoud Y. Madi, Yassine Kilani, Hayden Rotramel, Michelle Baliss, Jill Elwing, Gregory Sayuk, Ahmad Bazarbashi

2020-Current year OA Pubs

Introduction Colorectal cancer (CRC) represents a major global health burden, significantly impacting mortality rates and healthcare systems worldwide. CRC screening through colonoscopy enables early detection and removal of precancerous polyps. While standard polypectomy suffices for small polyps, larger ones require endoscopic mucosal resection (EMR). Though post-EMR surveillance is crucial for preventing recurrence, it remains unclear whether follow-up by general gastroenterologists yields comparable outcomes to surveillance by interventional specialists. This distinction carries significant implications for resource allocation, particularly given the limited availability of interventional gastroenterologists whose expertise is needed for other complex procedures. Our study examines this unexplored question by comparing …

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 …

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 …

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 …

Development And Validation Of A Prechiasmatic Mouse Model Of Subarachnoid Hemorrhage To Measure Long-Term Cognitive Deficits, Deepti Diwan, Jogender Mehla, James W Nelson, James D Quirk, Sheng-Kwei Song, Sarah Cao, Benjamin Meron, Aminah Mostofa, Gregory J Zipfel

2020-Current year OA Pubs

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced …

Fibrolytic Vaccination Against Adam12 Reduces Desmoplasia In Preclinical Pancreatic Adenocarcinomas, Jing Chen, David Denardo, Et Al.

2020-Current year OA Pubs

A hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12

Subcutaneous Ocrelizumab In Multiple Sclerosis: Results Of The Phase 1b Ocarina I Study, Scott D Newsome, Robert T Naismith, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).

METHODS: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 …

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, …

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 …

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 …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Rachel L Henson, Beau Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

METHODS: We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium-Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Genomic Insights For Personalised Care In Lung Cancer And Smoking Cessation: Motivating At-Risk Individuals Toward Evidence-Based Health Practices, Tony Chen, Giang Pham, Louis Fox, Alex T Ramsey, Laura J Bierut, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes.

METHODS: We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardised PRS distributions across all ancestries. We validated our PRSs in 561,776 individuals of diverse ancestry …