Digital Commons Network^™

A Draft Human Pangenome Reference, Wen-Wei Liao, Haley J Abel, Robert S Fulton, Chad Tomlinson, Lucinda L Antonacci-Fulton, Sarah Cody, Allison A Regier, Ting Wang, Et Al.

2020-Current year OA Pubs

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals

Neighborhood Deprivation And Association With Neonatal Intensive Care Unit Mortality And Morbidity For Extremely Premature Infants, Brynne A Sullivan, Ayush Doshi, Pavel Chernyavskiy, Ameena Husain, Alexandra Binai, Rakesh Sahni, Karen D Fairchild, J Randall Moorman, Colm P Travers, Zachary A Vesoulis

2020-Current year OA Pubs

IMPORTANCE: Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.

OBJECTIVE: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 …

First-In-Human Phase Ib Trial Of M9241 (Nhs-Il12) Plus Avelumab In Patients With Advanced Solid Tumors, Including Dose Expansion In Patients With Advanced Urothelial Carcinoma, Julius Strauss, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: In preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.

METHODS: In the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg …

A Randomized, Open-Label Study Of The Tolerability And Efficacy Of One Or Three Daily Doses Of Ivermectin Plus Diethylcarbamazine And Albendazole (Ida) Versus One Dose Of Ivermectin Plus Albendazole (Ia) For Treatment Of Onchocerciasis, Nicholas O. Opoku, Nicole Fetcho, Kerstin Fischer, Peter U. Fischer, Charles W. Goss, Augustine R. Hong, Daphne Lew, Gary J. Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis.

METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with …

Chemotherapy-Induced Toxicities: An Imaging Primer, Nikhil S. Patil, Natasha Larocque, Christian B. Van Der Pol, Carlos Torres, Demetrios A. Raptis, Michael N. Patlas

2020-Current year OA Pubs

The Coronavirus Disease of 2019 (COVID-19) pandemic has caused significant delays in the delivery of cancer treatments in Canada. As cancer treatment and imaging volumes return to normal, radiologists will encounter more cases of chemotherapy-induced toxicities. These toxicities have varied appearances on imaging, and can affect multiple organ systems. The purpose of this review is to offer a unified resource for general radiologists regarding the imaging appearances of chemotherapy-induced toxicities.

Blockade Of Trpv Channels By Intracellular Spermine, Grigory Maksaev, Peng Yuan, Colin G Nichols

2020-Current year OA Pubs

The Vanilloid thermoTRP (TRPV1-4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two …

Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva

2020-Current year OA Pubs

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant …

Association Of Sex With Neurobehavioral Markers Of Executive Function In 2-Year-Olds At High And Low Likelihood Of Autism, Tanya St John, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored.

OBJECTIVE: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL …

Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman

2020-Current year OA Pubs

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD. Our screen identifies 15 genetic enhancers of αSyn-induced progressive locomotor dysfunction, including knockdown of fly homologs of GBA …

Identifying Regions Of Interest In Mammogram Images, Shu Jiang, Jiguo Cao, Graham A. Colditz

2020-Current year OA Pubs

Screening mammography is the primary preventive strategy for early detection of breast cancer and an essential input to breast cancer risk prediction and application of prevention/risk management guidelines. Identifying regions of interest within mammogram images that are associated with 5- or 10-year breast cancer risk is therefore clinically meaningful. The problem is complicated by the irregular boundary issue posed by the semi-circular domain of the breast area within mammograms. Accommodating the irregular domain is especially crucial when identifying regions of interest, as the true signal comes only from the semi-circular domain of the breast region, and noise elsewhere. We address …

Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby

2020-Current year OA Pubs

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, …

Quantitative Determination Of Slc2a1 Variant Functional Effects In Glut1 Deficiency Syndrome, Naeimeh Tayebi, Brian Leon-Ricardo, Kevin Mccall, Elvisa Mehinovic, Kristin Engelstad, Vincent Huynh, Tychele N Turner, Judy Weisenberg, Liu L Thio, Paul Hruz, Robin S B Williams, Darryl C De Vivo, Vincent Petit, Gabe Haller, Christina A Gurnett

2020-Current year OA Pubs

OBJECTIVE: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.

METHODS: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD …

Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al.

2020-Current year OA Pubs

BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy.

METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to …

Treatment And Disposal Practices Of Pharmaceutical Effluent Containing Potential Antibiotic Residues In Two States In India And Perceptions Of Various Stakeholders On Contribution Of Pharmaceutical Effluent To Antimicrobial Resistance: A Qualitative Study, Anita Kotwani, Ajita Kapur, Mihir Chauhan, Sumanth Gandra

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance (AMR) is a looming pandemic, demanding prompt actions to avert catastrophic consequences. Effluents from pharmaceutical industries containing antimicrobial residues could serve as one of the entry points of these drugs to the environment. This qualitative study explores the treatment and disposal practices of pharmaceutical effluent (PE) containing potential antibiotic residues (ARs) by interviewing major stakeholders. In addition, we assessed their knowledge and perception on contribution of PE to AMR.

METHODS: The study was conducted in the two Indian states, Haryana and Telangana and at the federal level. Data was collected by semi-structured in-depth interviews of 29 participants …

A Phase 1 First-In-Human Study Of Gs-0189, An Anti-Signal Regulatory Protein Alpha (Sirpα) Monoclonal Antibody, In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (Nhl), Mayur Narkhede, Nancy L Bartlett, Sami Ibrahimi, Leslie Popplewell, Anna Seto, Jamie Bates, Yeonju Lee, Vaishnavi Ganti, Ling Han, Tianling Chen, Manish R Patel

2020-Current year OA Pubs

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS-0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); …

Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.

2020-Current year OA Pubs

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …

Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill

2020-Current year OA Pubs

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes …

Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi

2020-Current year OA Pubs

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, …

Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen

2020-Current year OA Pubs

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …

Belimumab Versus Anifrolumab In Adults With Systemic Lupus Erythematosus: An Indirect Comparison Of Clinical Response At 52 Weeks, Binod Neupane, Pragya Shukla, Mahmoud Slim, Amber Martin, Michelle Petri, George K. Bertsias, Alfred H J Kim, Antonis Fanouriakis, Roger A. Levy, Deven Chauhan, Nick Ballew

2020-Current year OA Pubs

OBJECTIVE: To generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices.

METHODS: The SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated with an indirect treatment comparison. The evidence base consisted of randomised trials that were compiled through a systemic literature review.A feasibility assessment was performed to comprehensively compare the eligible trials and to determine the most appropriate indirect treatment comparison analysis method. A multilevel network meta-regression (ML-NMR) was implemented that adjusted for differences across trials in four baseline characteristics: SLE Disease Activity Index-2K, anti-double-stranded DNA antibody positive, low …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Grant V Bochicchio, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

Usefulness Of The Lupus Low Disease Activity State As A Treatment Target In Childhood-Onset Sle, Ellen M. Cody, Bridget E. Wilson, Ekemini A. Ogbu, Jennifer L. Huggins, Chen Chen, Tingting Qiu, Tracy V. Ting, Francisco Flores, Bin Huang, Hermine I. Brunner

2020-Current year OA Pubs

OBJECTIVE: Treat-to-target (T2T) strategies are advocated to improve prognosis in childhood-onset SLE (cSLE). Proposed T2T states include SLEDAI score of

METHODS: Longitudinal data from 165 patients enrolled in the Cincinnati Lupus Registry were included. LN presence was based on renal biopsy, and patients were followed up until 18 years of age.

RESULTS: The 165 patients (LN: 45, white: 95) entered the registry within a median of 0 (IQR: 0-1) year post diagnosis and were followed up for a median of 4 (IQR: 2-5) years during which 80%, 92% and 94% achieved LLDAS, low-CS and SLEDAI-LD. Patients with LN were significantly …

Leveraging Innovation To Mitigate Risk During Heart Surgery, Marc R Moon, Puja Kachroo

2020-Current year OA Pubs

No abstract provided.

Influence Of Genomic Landscape On Cancer Immunotherapy For Newly Diagnosed Ovarian Cancer: Biomarker Analyses From The Imagyn050 Randomized Clinical Trial, Charles N Landen, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.

PATIENTS AND METHODS: Patients with newly diagnosed ovarian cancer were randomized to either atezolizumab or placebo with standard chemotherapy and bevacizumab. Programmed death-ligand 1 (PD-L1) status of tumor-infiltrating immune cells (IC) was determined centrally (VENTANA SP142 assay). Genomic alterations, including deleterious BRCA1/2 alterations, genomic loss of heterozygosity (gLOH), tumor mutation burden (TMB), and microsatellite instability (MSI), were evaluated using the FoundationOne assay. HRD was defined as gLOH ≥ 16%, regardless of BRCA1/2 mutation status. Potential associations …

Genomic Complexity Predicts Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Hormone Receptor-Positive (Hr+)/Her2-Negative Metastatic Breast Cancer, Andrew A Davis, Jingqin Luo, Rama Suresh, Foluso O Ademuyiwa, Caron Rigden, Timothy P Rearden, Katherine Clifton, Katherine Weilbaecher, Ashley Frith, Tracy Summa, Brittney Haas, Shana Thomas, Leonel F Hernandez-Aya, Lindsay L Peterson, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance.

EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome …

Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu

2020-Current year OA Pubs

Identifying complete response (CR) after rectal cancer preoperative treatment is critical to deciding subsequent management. Imaging techniques, including endorectal ultrasound and MRI, have been investigated but have low negative predictive values. By imaging post-treatment vascular normalization using photoacoustic microscopy, we hypothesize that co-registered ultrasound and photoacoustic imaging will better identify complete responders. In this study, we used

Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang

2020-Current year OA Pubs

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …

Examining Mental Health, Education, Employment, And Pain In Sickle Cell Disease, Kelly M Harris, Liliana Preiss, Taniya Varughese, Anna Bauer, Cecelia L Calhoun, Marsha Treadwell, Rita Masese, Jane S Hankins, Faiz Ahmed Hussain, Jeffrey Glassberg, Cathy L Melvin, Robert Gibson, Allison A King, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

IMPORTANCE: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain.

OBJECTIVE: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD.

DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022.

MAIN …

Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint

2020-Current year OA Pubs

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …

The Natural History Of Curve Behavior After Brace Removal In Adolescent Idiopathic Scoliosis: A Literature Review, Scott Luhmann, Daphna Zaaroor-Regev, Vidyadhar V Upasani, Harry Shufflebarger

2020-Current year OA Pubs

PURPOSE: Brace treatment is the most common nonoperative treatment to prevent curve progression in adolescent idiopathic scoliosis (AIS). The goal of this review and analysis is to characterize curve behavior after completion of brace treatment and to identify factors that may facilitate the estimation of long-term curve progression.

METHOD: A review of the English language literature was completed using the MEDLINE (PUBMED) database of publications after 1990 until September 2020. Studies were included if they detailed a minimum of 1 year post-brace removal follow-up of AIS patients. Data retrieved from the articles included Cobb angle measurements of the major curves …