tbuckley/cabot-search huggingface dataset:
Polygenic Risk and Progression to Bipolar or Psychotic Disorders Among Individuals Diagnosed With Unipolar Depression in Early Life
Authors: Katherine L. Musliner, Morten D. Krebs, Clara Albiñana, Bjarni Vilhjalmsson, Esben Agerbo, Peter P. Zandi, David M. Hougaard, Merete Nordentoft, Anders D. Børglum, Thomas Werge, Preben B. Mortensen, Søren D. Østergaard
Journal: American Journal of Psychiatry (2020)

The authors investigated the associations between polygenic liability and progression to bipolar disorder or psychotic disorders among individuals diagnosed with unipolar depression in early life.A cohort comprising 16,949 individuals (69% female, 10-35 years old at the first depression diagnosis) from the iPSYCH Danish case-cohort study (iPSYCH2012) who were diagnosed with depression in Danish psychiatric hospitals from 1994 to 2016 was examined. Polygenic risk scores (PRSs) for major depression, bipolar disorder, and schizophrenia were generated using the most recent results from the Psychiatric Genomics Consortium. Hazard ratios for each disorder-specific PRS were estimated using Cox regressions with adjustment for the other two PRSs. Absolute risk of progression was estimated using the cumulative hazard.Patients were followed for up to 21 years (median=7 years, interquartile range, 5-10 years). The absolute risks of progression to bipolar disorder and psychotic disorders were 7.3% and 13.8%, respectively. After mutual adjustment for the other PRSs, only the PRS for bipolar disorder predicted progression to bipolar disorder (adjusted hazard ratio for a one-standard-deviation increase in PRS=1.11, 95% CI=1.03, 1.21), and only the PRS for schizophrenia predicted progression to psychotic disorders (adjusted hazard ratio=1.10, 95% CI=1.04, 1.16). After adjusting for PRSs, parental history still strongly predicted progression to bipolar disorder (adjusted hazard ratio=5.02, 95% CI=3.53, 7.14) and psychotic disorders (adjusted hazard ratio=1.63, 95% CI=1.30, 2.06).PRSs for bipolar disorder and schizophrenia are associated with risk for progression to bipolar disorder or psychotic disorders, respectively, among individuals diagnosed with depression; however, the effects are small compared with parental history, particularly for bipolar disorder.
Abstract 12670: Comparison Of A Novel Method Vs The Friedewald Equation For Low Density Lipoprotein Cholesterol Estimation In Patients With Hypertriglyceridemia
Authors: Aparna Sajja, Vasanth Sathiyakumar, Jihwan Park, Vincent Pallazola, Eliseo Guallar, Mariano Lazo, Steven R Jones, Seth S Martin
Journal: Circulation (2019)

Introduction: Clinicians often receive the lab message that LDL-C could not be calculated if TG level is 400-499 mg/dL, given concern for chylomicrons. Reflexing to direct LDL-C assays in this sett...
Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis
Authors: Debra T. Choi, Jessica A. Davila, Shubhada Sansgiry, Eric David, Hardeep Singh, Hashem B. El-Serag, Yvonne Hsiao-Fan Sada
Journal: Clinical Gastroenterology and Hepatology (2020)
Sustained depletion of FXIII-A by inducing acquired FXIII-B deficiency
Authors: Amy W. Strilchuk, Scott C. Meixner, Jerry Leung, Nooshin S. Safikhan, Jayesh A. Kulkarni, Hannah M. Russell, Roy van der Meel, Michael R. Sutherland, A. Phillip Owens, Joseph S. Palumbo, Edward M. Conway, Edward L. G. Pryzdial, Pieter R. Cullis, Christian J. Kastrup
Journal: Blood (2020)
Fast processes of nanoparticle blood clearance: Comprehensive study
Authors: Ivan V. Zelepukin, Alexey V. Yaremenko, Mikhail V. Yuryev, Aziz B. Mirkasymov, Ilya L. Sokolov, Sergey M. Deyev, Petr I. Nikitin, Maxim P. Nikitin
Journal: Journal of Controlled Release (2020)
Antibody targeting of phosphatidylserine produces a cytokine microenvironment that enhances innate anti-tumor immune responses
Authors: Monica Friedrich, Claudia Guevara, Daniel Falcon, Kristifer Garcia, Cristy Bautista, Connie Chang, Bruce Freimark
Journal: Cancer Research (2008)

4079  Anionic phospholipids, principally phosphatidylserine (PS), become exposed on the external surface of vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. PS exposure on cells (e.g. during apoptosis) causes macrophages to produce anti-inflammatory cytokines, leading to the engulfment of the dying cells without induction of inflammation. In the present study, we evaluate the ability of a panel of chimeric and human antibodies to exert anti-tumor effects through various mechanisms, including ADCC on cellular targets expressing PS and modulation of pro-inflammatory cytokines and chemokine production. In the presence of antibodies that target PS, human peripheral blood mononuclear cells mediate specific killing of human tumor cells treated with paclitaxel or etoposide and enhance the production of TNFα by human monocytes in vitro. In addition, preliminary data indicate that bavituximab modulates the production of tumor-derived chemokines in vitro. Current studies are in progress to evaluate the anti-tumor response of chimeric and human anti-PS antibodies in NOD/SCID mice. Single-dose pharmacokinetic analysis of bavituximab in NOD/SCID mice was similar to previous studies conducted in immune competent rats and non-human primates. These data suggest that multiple cellular and cytokine/chemokine responses in the tumor microenvironment may contribute to the anti-tumor activities of bavituximab.
The Effects of High-Protein Diets on Kidney Health and Longevity
Authors: Gang-Jee Ko, Connie M. Rhee, Kamyar Kalantar-Zadeh, Shivam Joshi
Journal: Journal of the American Society of Nephrology (2020)

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to
A Machine Learning Approach to Understanding Patterns of Engagement With Internet-Delivered Mental Health Interventions
Authors: Isabel Chien, Angel Enrique, Jorge Palacios, Tim Regan, Dessie Keegan, David Carter, Sebastian Tschiatschek, Aditya Nori, Anja Thieme, Derek Richards, Gavin Doherty, Danielle Belgrave
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The mechanisms by which engagement with internet-delivered psychological interventions are associated with depression and anxiety symptoms are unclear. <h3>Objective</h3> To identify behavior types based on how people engage with an internet-based cognitive behavioral therapy (iCBT) intervention for symptoms of depression and anxiety. <h3>Design, Setting, and Participants</h3> Deidentified data on 54 604 adult patients assigned to the Space From Depression and Anxiety treatment program from January 31, 2015, to March 31, 2019, were obtained for probabilistic latent variable modeling using machine learning techniques to infer distinct patient subtypes, based on longitudinal heterogeneity of engagement patterns with iCBT. <h3>Interventions</h3> A clinician-supported iCBT-based program that follows clinical guidelines for treating depression and anxiety, delivered on a web 2.0 platform. <h3>Main Outcomes and Measures</h3> Log data from user interactions with the iCBT program to inform engagement patterns over time. Clinical outcomes included symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder-7 [GAD-7]); PHQ-9 cut point greater than or equal to 10 and GAD-7 scores greater than or equal to 8 were used to define depression and anxiety. <h3>Results</h3> Patients spent a mean (SD) of 111.33 (118.92) minutes on the platform and completed 230.60 (241.21) tools. At baseline, mean PHQ-9 score was 12.96 (5.81) and GAD-7 score was 11.85 (5.14). Five subtypes of engagement were identified based on patient interaction with different program sections over 14 weeks: class 1 (low engagers, 19 930 [36.5%]), class 2 (late engagers, 11 674 [21.4%]), class 3 (high engagers with rapid disengagement, 13 936 [25.5%]), class 4 (high engagers with moderate decrease, 3258 [6.0%]), and class 5 (highest engagers, 5799 [10.6%]). Estimated mean decrease (SE) in PHQ-9 score was 6.65 (0.14) for class 3, 5.88 (0.14) for class 5, and 5.39 (0.14) for class 4; class 2 had the lowest rate of decrease at −4.41 (0.13). Compared with PHQ-9 score decrease in class 1, the Cohen<i>d</i>effect size (SE) was −0.46 (0.014) for class 2, −0.46 (0.014) for class 3, −0.61 (0.021) for class 4, and −0.73 (0.018) for class 5. Similar patterns were found across groups for GAD-7. <h3>Conclusions and Relevance</h3> The findings of this study may facilitate tailoring interventions according to specific subtypes of engagement for individuals with depression and anxiety. Informing clinical decision needs of supporters may be a route to successful adoption of machine learning insights, thus improving clinical outcomes overall.
OP0061 Recombinant osteoprotegerin (opg) regulates bone erosions and osteoclast numbers in a schedule-dependent manner in joints of male lewis rats with adjuvant arthritis
Authors: U Feige, G Campagnuolo, B Bolon
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Our laboratory has shown that bone destruction in the Lewis rat model of adjuvant arthritis (AdA) can be significantly reduced by daily administration of recombinant human osteoprotegerin (rhOPG) if treatment is initiated at the onset of clinical arthritis.<sup>1</sup> <h3>Objectives</h3> The current study was performed to assess the ability of rhOPG to spare bone using an abbreviated dosing schedule. <h3>Methods</h3> AdA was induced in male Lewis rats (8 weeks old, n = 6/group) on Day 0; clinical arthritis (indicated by hind paw swelling) developed on Day 9. Arthritic animals received rhOPG (daily s.c. bolus of 4 mg/kg) by one of four schedules: no rhOPG (Group 1, control for AdA induction); daily rHOPG, Days 9 to 15 (Group 2, control for rhOPG efficacy); early intervention, Days 9 to 11 (Group 3); or delayed intervention, Days 13 to 15 (Group 4). Rats were necropsied on Day 16, and bone mineral density [BMD] of bones in the tibiotarsal (ankle) joint was measured by DEXA (dual X-ray absorptiometry). Next, sections of formalin-fixed, decalcified, paraffin-embedded hind paws were stained by an indirect immunohistochemical method to detect cathepsin K, an osteoclast marker. Histopathologic scores to assess lesion severity (given below as group means ± standard deviation) were acquired for inflammation, bone erosion, and osteoclast numbers using tiered, semi-quantitative grading scales. <h3>Results</h3> Joints of vehicle-treated arthritic animals (Group 1) exhibited measurable loss of BMD as well as extensive inflammation (4.0 ± 0), skeletal erosion (4.5 ± 0.5), and osteoclast production (4.0 ± 0). As noted previously,<sup>2</sup> rhOPG therapy throughout the 7-day clinical course of AdA (Group 2) preserved BMD and almost completely inhibited erosions (1.2 ± 0.4) and osteoclastogenesis (0.8 ± 0.8) but did not modify the extent of inflammation (3.7 ± 0.5). Early initiation of rhOPG treatment (Group 3) yielded similar retention of BMD as well as reductions in erosion (1.2 ± 0.4) and osteoclast (1.7 ± 0.5) scores. However, in comparison to Groups 2 and 3, delayed rhOPG administration (Group 4) protected BMD and lowered the mean osteoclast score (2.0 ± 0.3) but was significantly less effective in preventing erosions (2.5 ± 1.4). <h3>Conclusion</h3> Our data indicate that early intervention with a bone-sparing agent such as rhOPG is needed to obtain the greatest clinical benefit with respect to protecting skeletal integrity in arthritic joints but also show that delayed rhOPG therapy can reduce the loss of joint BMD even in the presence of severe inflammation. <h3>References</h3> Kong, et al. Nature 1999;402:304 Feige, et al. Ann Rheum Dis. 2000;59(Suppl I):148
Over-expression of IL-6 can contribute to tumor growth by altered promoter methylation and gene expression in human cholangiocarcinoma.
Authors: Hania Wehbe, Roger Henson, Fanyin Meng, Janna Mize-Berge, Molly Lang, Tushar Patel
Journal: Cancer Research (2006)

5127  Background: Cholangiocarcinomas are cancers of the biliary tract that arise in the setting of chronic biliary tract inflammation. The inflammation-associated cytokine IL-6 is over-expressed in cholangiocarcinoma, and promotes tumor growth. However the mechanisms by which over-expression of IL-6 contributes to tumor growth or formation remain unknown. Recently, IL-6 has been shown to regulate activity of DNA methyltransferases. By altering DNA methylation, IL-6 could regulate gene expression. Thus, our aim was to assess the effect of IL-6 over-expression on gene expression, and to identify potential target genes that are epigenetically regulated. Methods: Mz-ChA-1, malignant human cholangiocarcinoma cells were stably transfected to over-express IL-6. Stable transfectants or their respective controls were treated with 0 or 5 μM 5’-Azacytidine, an inhibitor of DNA methylation. Tumor cell growth was assessed by cell proliferation assays, and anchorage independent growth in soft agar. Genomic DNA was isolated and analyzed for 5-methyl-cytosine content. Methylation of selected gene promoters was assessed using the TransSignal Methylation Array. Gene expression was assessed by microarray analysis using Affymetrix U133A chips, and analyzed using GeneSifter. The expression of the receptor for the biliary epithelial mitogen EGF was assessed by Western blot analysis. Results: Treatment with 5’-Azacytidine decreased Mz-ChA-1 cell proliferation and growth in soft agar. 5’-Azacytidine decreased methylcytosine in controls, but not in IL-6 over-expressing cells. Moreover, 5’-Azacytidine did not alter cell proliferation or growth in soft agar in IL-6 over-expressing cells. Thus, overexpression of IL-6 prevented the effects of 5’-Azacytidine on tumor cell growth. The expression of several genes was altered in cells over-expressing IL-6. An increased methylation of the promoters of several genes such as survivin, HoxA2 and caspase 8 was observed in IL-6 over-expressing cells. However, promoter methylation of several oncogenes such as K-ras and Rb was not observed. The expression of the EGF receptor was decreased by 5’-Azacytidine, but was increased by IL-6 over-expression. Summary and Conclusion: Over-expression of IL-6 can modulate gene expression and tumor cell growth by altering gene-specific methylation and expression of growth regulatory pathways such as those involving the EGF receptor. Moreover, enhanced IL-6 expression may decrease the sensitivity of tumor cells to methylation inhibitors. We conclude that dysregulation of promoter methylation and gene expression is an important mechanism by which IL-6 contributes to tumor progression. These observations provide a mechanism by which persistent cytokine stimulation can promote tumor growth.
The Hydrocortisone vs Pasireotide in Reducing Pancreatic Surgery Complications Noninferiority Trial
Authors: Alfred Adiamah, Anisa Kushairi, Dhanwant Gomez
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2
Authors: Zhiqiang Zheng, Vanessa Marthe Monteil, Sebastian Maurer-Stroh, Chow Wenn Yew, Carol Leong, Nur Khairiah Mohd-Ismail, Suganya Cheyyatraivendran Arularasu, Vincent Tak Kwong Chow, Raymond Tzer Pin Lin, Ali Mirazimi, Wanjin Hong, Yee-Joo Tan
Journal: Eurosurveillance (2020)

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.
The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol in Diabetes
Authors: Ronald B. Goldberg, Neil J. Stone, Scott M. Grundy
Journal: Diabetes Care (2020)

The American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines recently published its 2018 recommendations on management of LDL cholesterol (LDL-C) in people with diabetes. For primary prevention, moderate-intensity statin therapy is recommended for those aged 40–75 years, with a preference for high-intensity statin treatment for older subjects and for those with higher estimated risk or risk-enhancing factors following a patient-clinician discussion. Statin therapy may be reasonable in adults &amp;lt;40 years or &amp;gt;75 years of age where there is less evidence for benefit. For people with diabetes and established atherosclerotic cardiovascular disease, high-intensity statin therapy is recommended. The majority of these subjects have very high risk, and an LDL-C goal of &amp;lt;70 mg/dL is recommended. If this target is not achieved, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor may be added.
FRI0195 Pupillocynetic activity of substance p in systemic sclerosis (ssc)
Authors: A Del Rosso, L Bertinotti, M Messori, U Pietrini, R Sicuteri, A Messori, M Fanciullacci, M Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In SSc a dysfunction of peripheral nervous system (PNS) has been showed. SP instillation in human eye induces a cholinergic-independent pupil miosis via specific receptors on neuroirideal junction. <h3>Objectives</h3> In order to study PNS function in SSc, we assessed by pupillometry pupil basal diameters and pupil ability to respond to SP instillation in SSc patients and in controls. <h3>Methods</h3> 32 SSc patients [17 with limited (lSSc) and 15 with diffuse SSc (dSSc)] and 30 controls underwent pupillometry for evaluating basal iris diameters in both eyes. Then, SP was instilled in one eye [treated eye (TE)] and placebo in the other eye [not treated eye (NTE)] and the pupil response to SP instillation was assessed both in TE and in NTE. In order to verify the existence of a dose-dependence activity of SP, two different SP concentrations (10–3 and 10–5 M) were tested separately. For both eyes, t0 (pupil basal diameter) and AUC (iris pharmacological response to SP instillation) were considered. 2-tailed t-test was used to compare TE with NTE within groups and SSc with HC. ANOVA, Scheffè and Dunnett post-hoc tests were utilised to compare lSSc, dSSc and HC. <h3>Results</h3> At t0, basal pupillary diameters of SSc resulted significantly minor in respect to HC (p &lt; .001) and significant differences between lSSc and dSSc and HC (p &lt; .05), but not between dSSc and HC, were found. Significant differences between SSc and controls were found in the response to SP 10–3 and 10–5, both for TE and for NTE (p &lt; .05 in all cases). The TE of lSSc showed a significant major miosis to SP 10–3 and 10–5 instillation vs dSSc and controls (p &lt; .05), whereas in the TE of dSSc pupillary miosis was not different from controls. In NTE, a significantly different miosis between lSSc and controls was induced by both SP concentrations (p &lt; .001), while a significant difference between lSSc and dSSc was found only when SP 10–3 M was used (p = .002). In dSSc, the instillation of SP 10–3, but not of SP 10–5 M, induced in NTE a more intense miosis in respect to controls NTE (p = .004). The comparison between TE and NTE was significantly different in controls (p &lt; .001), but not in lSSc and in dSSc. <h3>Conclusion</h3> Our results show that lSSc is characterised by the involvement of neuroirideal junction. In fact, the irideal basal diameter is reduced, and SP induces a more intense miosis in respect both to dSSc and to HC. The lack of difference between TE and NTE could be due to a dysfunction of peripheral nervous system, more likely involving central control mechanisms.
Correction: S100A6 is a critical regulator of hematopoietic stem cells
Authors: Tan Hooi Min Grahn, Abhishek Niroula, Ákos Végvári, Leal Oburoglu, Maroulio Pertesi, Sarah Warsi, Fatemeh Safi, Natsumi Miharada, Sandra Capellera-Garcia, Kavitha Siva, Yang Liu, Emma Rörby, Björn Nilsson, Roman A. Zubarev, Stefan Karlsson
Journal: Leukemia (2020)
A Phase I/II Study of Veliparib (ABT-888) in Combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer
Authors: Michael J. Pishvaian, Hongkun Wang, Aiwu Ruth He, Jimmy J. Hwang, Brandon G. Smaglo, Sunnie S. Kim, Benjamin A. Weinberg, Louis M. Weiner, John L. Marshall, Jonathan R. Brody
Journal: Clinical Cancer Research (2020)

Up to 17% of patients with pancreatic ductal adenocarcinoma (PDAC) harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as