tbuckley/cabot-search huggingface dataset:
Abstract P285: Sociodemographic and Metabolic Risk Characteristics Associated with Metabolic Weight Categories in the Women's Health Initiative
Authors: Amber R Cordola Hsu, Susan L Ames, Bin Xie, Darleen V Peterson, Lorena Garcia, Scott B Going, Nathan D Wong, Hoda Anton-Culver
Journal: Circulation (2020)

Introduction: To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women. Hypothesis: We assessed the hypothesis that postmenopausal women with metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) were more likely to have adverse risk factors as compared to those with metabolically healthy normal weight (MHNW). Methods: The Women’s Health Initiative (WHI) enrolled 161,808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n=19,412). Normal weight was defined as a body-mass index (BMI) ≥18.5 and &lt;25 kg/m 2 and waist circumference (WC) &lt;88 cm and overweight/obesity as a BMI &gt; 25 kg/m 2 or WC &gt; 88 cm. Metabolically healthy was based on &lt;2 and metabolically unhealthy &gt; 2 traits: triglycerides &gt; 150 mg/dl, systolic blood pressure (BP) &gt; 130 mmHg or diastolic BP &gt; 85 mmHg or antihypertensives or diuretics, fasting glucose &gt; 100 mg/dl or diabetes medication, and HDL-cholesterol &lt;50 mg/dl. Multinomial logistic regression with generalized link logit function provided the odds ratio (ORs) of MHNW, MUHNW, MHO and MUHO. Results: The table shows the ORs of risk factors and biomarkers. Among the 19,412 participants, 2,369 (12.2%) had prevalent diabetes and a mean age of 63.3 ± 0.05 (SEM). Advanced age was associated with a greater odds of MUHNW and a lower odds of MHO as compared to the MHNW after adjusting for covariates. African-Americans were associated with a decreased likelihood of MUHNW and MUHO, while Hispanics were associated with a decreased likelihood of MHO and MUHO as compared to MHNW. Low-income had a greater odds of MUHNW, yet high-income had a lower odds of MHO or MUHO. Total cholesterol, insulin and C-reactive protein were associated with a greater odds of MUHNW, MUHO or MHO. Conclusions: Advanced age, ethnicity, income and biomarkers are important indicators of metabolic weight categories among postmenopausal women.
Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons
Authors: Chloé Berland, Enrica Montalban, Elodie Perrin, Mathieu Di Miceli, Yuko Nakamura, Maud Martinat, Mary Sullivan, Xue S. Davis, Mohammad Ali Shenasa, Claire Martin, Stefania Tolu, Fabio Marti, Stephanie Caille, Julien Castel, Sylvie Perez, Casper Gravesen Salinas, Chloé Morel, Jacob Hecksher-Sørensen, Martine Cador, Xavier Fioramonti, Matthias H. Tschöp, Sophie Layé, Laurent Venance, Philippe Faure, Thomas S. Hnasko, Dana M. Small, Giuseppe Gangarossa, Serge H. Luquet
Journal: Cell Metabolism (2020)
Strengths and weaknesses of dosimetry used in studies of low-dose radiation exposure and cancer
Authors: R D Daniels, G Kendall, I Thierry-Chef, M S Linet, H M Cullings
Journal: JNCI Journal of the National Cancer Institute (2020)

Background  A monograph systematically evaluating recent evidence on the dose-response relationship between low-dose ionizing radiation exposure and cancer risk required a critical appraisal of dosimetry methods in 26 potentially informative studies.  Methods  The relevant literature included studies published in 2006-2017. Studies comprised case-control and cohort designs examining populations predominantly exposed to sparsely ionizing radiation, mostly from external sources, resulting in average doses of no more than 100 mGy. At least two dosimetrists reviewed each study and appraised the strengths and weaknesses of the dosimetry systems used, including assessment of sources and effects of dose estimation error. An overarching concern was whether dose error might cause the spurious appearance of a dose-response where none was present.  Results  The review included 8 environmental, 4 medical, and 14 occupational studies that varied in properties relative to evaluation criteria. Treatment of dose estimation error also varied among studies, although few conducted a comprehensive evaluation. Six studies appeared to have known or suspected biases in dose estimates. The potential for these biases to cause a spurious dose-response association was constrained to three case-control studies that relied extensively on information gathered in interviews conducted after case ascertainment.  Conclusions  The potential for spurious dose-response associations from dose information appeared limited to case-control studies vulnerable to recall errors that may be differential by case status. Otherwise, risk estimates appeared reasonably free of a substantial bias from dose estimation error. Future studies would benefit from a comprehensive evaluation of dose estimation errors, including methods accounting for their potential effects on dose-response associations.
A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon- α2a as first-line therapy in metastatic renal cell carcinoma
Authors: B. Escudier, P. Koralewski, A. Pluzanska, A. Ravaud, S. Bracarda, C. Szczylik, C. Chevreau, M. Filipek, B. Melichar, N. Moore
Journal: Journal of Clinical Oncology (2007)

3 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumor angiogenesis by targeting VEGF. In relapsed RCC, BEV improved time to progression compared with placebo (2.5 vs. 4.8 months). A phase III trial was conducted to evaluate the efficacy and safety of BEV in combination with interferon (IFN)-a2a as first-line treatment in metastatic (m) RCC. The final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS) are presented. Methods: Nephrectomized patients with clear cell mRCC, KPS of =70%, no CNS metastases and adequate organ function received IFN- a2a (x3/week at a recommended dose of 9 MIU for up to 1 year) plus BEV (10mg/kg q2w) or placebo until disease progression. Tumor assessments were performed every 8 weeks until week 32 and 12 weekly thereafter. Patients were stratified according to country and Motzer score. Results: Between June 2004 and October 2006, 649 patients were randomized (641 treated) at 101 centers in 18 countries. The treatment arms were well balanced for prognostic factors. At the data cutoff, 505 progression events had occurred, 111 patients remained on treatment, 287 had discontinued (discontinuations due to AEs were 12% with IFN vs. 28% with IFN-a2a/BEV), and 251 died. BEV-related side effects were generally mild and consistent with previous observations. The addition of BEV to IFN-a2a significantly increased PFS (10.2 vs. 5.4 mo) (HR=0.63; p&lt;0.0001) and objective tumor response rate (30.6% vs. 12.4%; p&lt;0.0001). A trend toward improved OS was observed with the addition of BEV to IFN-a2a (p=0.0670). Conclusions: BEV improves PFS when combined with IFN-a2a in mRCC. No unexpected safety events were observed. [Table: see text] [Table: see text]
Abstract 12630: Genetic Association of Arterial Stiffness Index With Incident Coronary Artery Disease and Congestive Heart Failure
Authors: Seyedeh M Zekavat, Mary Haas, Krishna Aragam, Connor Emdin, Amit V Khera, Derek Klarin, Hongyu Zhao, Pradeep Natarajan
Journal: Circulation (2018)

Introduction: Arterial stiffness index (ASI) is a noninvasive, rapid measurement extracted from finger infrared analysis. ASI has been independently associated with cardiovascular disease risk in m...
Coronavirus disease 2019 (covid-19): a guide for UK GPs
Authors: Mohammad S Razai, Katja Doerholt, Shamez Ladhani, Pippa Oakeshott
Journal: BMJ (2020)

What you need to know• Consider covid-19 infection in anyone with a new continuous cough, temperature ≥37.8 o C, flu like illness, pneumonia, or breathlessness • Any person with a new continuous cough and/or high temperature must self-isolate for seven days from the onset of symptoms, and asymptomatic household members should stay at home for 14 days • Triage all patients online or by phone to assess the need for face-to-face appointments.Use remote consultations when possible • When seeing patients suspected to have covid-19 who are unwell and require in-person assessment, wear personal protective equipment (PPE) and separate the consultation in time or place from other patients in the surgery.Subject to local risk assessment, PPE may also be indicated for routine medical work, regardless of the patient's status, in settings where there is sustained transmission of covid-19 • GP surgeries should develop protocols for managing patients with possible infection, including triaging remotely, postponing non-urgent services, isolation procedures, PPE provision, seeking specialist advice, decontamination, and collaborating with community services The UK recorded its first confirmed case of acute respiratory infection due to coronavirus disease 2019 (covid-19) on 31 January 2020 and initially responded by quarantining at-risk individuals to contain the spread of infection.However, when covid-19 cases increased and containment was no longer effective, the UK moved to a delay phase of the response on 12 March 2020.Executive agencies Public Health England (PHE), 1 Health Protection Scotland (HPS), and NHS England have since published updated guidance for healthcare providers on managing patients suspected to have covid-19.Guidance for the public and health professionals varies internationally, depending partly on risk levels and healthcare systems, and is being regularly updated.This article offers a practical guide for GPs and others working in UK primary care on when to suspect covid-19 and how to respond.It is based on current UK guidance at the time of publication and was updated on 3 April 2020.We recommend readers consult the latest guidance (box 1). Box 1: Essential resourcesCovid-19: latest case definition, investigation, and initial clinical management of possible cases: https://www.gov.uk/government/publications/wuhan-novel-coronavirusinitial-investigation-of-possible-cases/investigation-and-initial-clinicalmanagement-of-possible-cases-of-wuhan-novel-coronavirus-wn-covinfection
Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial
Authors: Michael J Pishvaian, Edik M Blais, Jonathan R Brody, Emily Lyons, Patricia DeArbeloa, Andrew Hendifar, Sam Mikhail, Vincent Chung, Vaibhav Sahai, Davendra P S Sohal, Sara Bellakbira, Dzung Thach, Lola Rahib, Subha Madhavan, Lynn M Matrisian, Emanuel F Petricoin
Journal: The Lancet Oncology (2020)
Activation of the Liver X Receptor Pathway Inhibits HBV Replication in Primary Human Hepatocytes
Authors: Jing Zeng, Daitze Wu, Hui Hu, John A.T. Young, Zhipeng Yan, Lu Gao
Journal: Hepatology (2020)

Hepatitis B virus (HBV) infection is ranked among the top health priorities worldwide. Accumulating evidence suggests that HBV infection and replication are closely associated with liver metabolism. The liver X receptors (LXRs), which belong to the superfamily of nuclear hormone receptors, are important physiological regulators of lipid and cholesterol metabolism. However, the association between the LXR pathway and HBV infection remains largely unclear.In this study, the antiviral activity of LXR agonists was investigated using multiple HBV cellular models. We observed that in HBV-infected primary human hepatocytes (PHHs), synthetic LXR agonists (T0901317, GW3965, and LXR-623), but not an LXR antagonist (SR9238), potently inhibited HBV replication and gene expression, as demonstrated by substantial reductions in viral RNA, DNA, and antigen production following agonist treatment. However, covalently closed circular DNA (cccDNA) levels were not significantly reduced by the agonists. In addition, no rebound in viral replication was observed after treatment withdrawal, indicating a long-lasting inhibitory effect. These results suggest that LXR agonists decrease the transcriptional activity of cccDNA. In contrast, no significant anti-HBV effect was observed in HepG2-derived cell lines. Interestingly, LXR agonist treatment strongly reduced cholesterol 7α-hydroxylase 1 (CYP7A1) mRNA levels. Knockdown of CYP7A1 gene expression with small interfering RNA inhibited HBV activity in PHHs, suggesting CYP7A1 as a potential factor contributing to the antiviral effects of LXR agonists.We found that activation of the LXR pathway with synthetic LXR agonists could elicit potent anti-HBV activity in PHHs, possibly through sustained suppression of cccDNA transcription. Our work highlights the therapeutic potential of targeting the LXR pathway for the treatment of chronic HBV infection.
Vaccination with a CEA epitope mimic leads to reduced growth of tumor transplants
Authors: K. Brämswig, R. Knittelfelder, S. Gruber, A. B. Riemer, R. Kammerer, W. Zimmermann, R. Horvat, C. C. Zielinski, O. Scheiner, E. Jensen-Jarolim
Journal: Journal of Clinical Oncology (2007)

3076 Background: The carcinoembryonic antigen (CEA) is a glycoprotein which is overexpressed on nearly 50% of all human tumors. We aimed to establish an active immunotherapy by replacing the poorly immunogenic glycoprotein with highly immunogenic peptides. Methods: Col-1 is a monoclonal antibody directed against CEA on tumor cells. To generate structural mimics of the Col-1 epitope, we used the Col-1 antibody and the biopanning method in order to select immunreactive peptide mimotopes from random phage libraries. Subsequently, immunogenicity of a selected mimotope was examined in BALB/c mice. We assessed antibody-dependent cytotoxicity (ADDC) and complement-dependent cytotoxicity (CDC) mediated by the induced antibodies on CEA expressing HT29 cells. Furthermore, after immunisation the BALB/c mice were transplanted subcutaneously with Meth-A/CEA tumor cells. Results: All peptides selected were exclusively recognized by the anti-CEA antibody. In addition, true mimicry of the peptides with the natural antigen was confirmed by competition ELISA using purified human CEA. The best mimotope was chosen for synthesis in a multiple antigenic peptide (MAP) configuration rendering, therefore, a multiple antigenic mimotope (MAM). BALB/c mice immunized with the MAM developed antibodies against the immunogen and the original antigen CEA. In vitro, the anti-mimotope antibodies were capable of inducing high specific lysis of CEA-expressing HT29 cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Moreover, after s.c tumor transplantation no tumor growth was seen in MAM immunized mice, compared to the groups receiving a control mimotope or the naïve group. The CEA-mimotope immunized group showed a capsuled necrotic region without tumor cells but granulocytes and limited vascularisation. The non treated group showed tumor cells in different proliferation stages and neovascularisation. Conclusions: We conclude that the Col-1 epitope of the glycoprotein CEA can be translated into an immunogenic peptide mimic. The mimotope-induced antibodies recognize CEA and do effectively inhibit growth of CEA positive tumors. Based on these findings we suggest that generated mimotopes are candidates for active immunotherapy of CEA- expressing tumors. No significant financial relationships to disclose.
Abstract P210: Associations Of Early Parental Feeding Concerns And Behaviors With Child’s Dietary Intakes Throughout Childhood
Authors: Veronique Gingras, Karen M Switkowski, Sheryl L Rifas-Shiman, Sabrina Faleschini, Emily Oken, Marie-France Hivert
Journal: Circulation (2020)

Introduction: Parental feeding behaviors have been found to be associated with dietary intakes and weight status in children, although the longitudinal associations of parental feeding behaviors in early life with diet later in childhood have been scarcely studied. Hypothesis: We hypothesized that parental feeding restriction, pressure to eat, and concerns about child’s weight would be associated with poorer diet quality throughout childhood. Methods: Among 1172 mother-child pairs from Project Viva, we examined associations of parental feeding behaviors at 2 years assessed via questions from the Child Feeding Questionnaire (behaviors dichotomized as yes vs. no) with diet quality in early (mean: 3.2, SD 0.2 years; n=1076) and mid-childhood (mean: 7.8, SD 0.7 years; n=993) assessed via food frequency questionnaires. We used linear regression models adjusted for socio-demographic characteristics, maternal and paternal body mass index, and maternal diet quality in pregnancy. Results: At 2 years postpartum, 47% of parents pressured/encouraged their child to eat more, 8% restricted their intakes, 15% were concerned about their child being overweight and 7% about their child being underweight. Parental pressure to eat at 2 years was associated with higher child intake of fruit juice (β 0.17 serving/day; 95% CI 0.01, 0.34) and snack foods (0.12 serving/day; 0.01, 0.22) in early childhood and with lower youth healthy eating index score (-1.32 points; -2.54, -0.10; score from 0 to 85 points) in mid-childhood. Parental feeding restriction at 2 years was associated with lower intake of sugar-sweetened beverages (-0.17 serving/day; -0.27, -0.06) in early childhood and with lower intake of dairy (-0.29 serving/day; -0.56, -0.02) in mid-childhood. Parental concerns about their child being underweight was associated with lower youth healthy eating index score (-2.18 points; -4.30, -0.05; score from 0 to 95 points) in early childhood while concerns about their child being overweight was associated with higher intakes of red and processed meat (0.14 serving/day; 0.04, 0.23) in early childhood and higher intake of baked products in mid-childhood (0.07 serving/day; 0.01, 0.13). Conclusions: We found that early parental feeding behaviors may have a modest contribution to dietary intakes throughout childhood. However, only a few associations persisted after adjusting for socio-economic and parental characteristics and effect sizes were modest. Strategies to improve diet quality in children might need to focus on the broader family and socio-economic context.
Early life factors for endometriosis: a systematic review
Authors: Karolína Olšarová, Gita D Mishra
Journal: Human Reproduction Update (2020)

Abstract BACKGROUND Despite its high prevalence and health burden, many aspects of endometriosis remain unclear, including risk factors and the underlying biological mechanisms. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition. To date, however, much of the evidence from studies on early life exposures and diagnosed endometriosis appears mixed and difficult to assess. OBJECTIVE AND RATIONALE This study aims to provide a systematic review of the epidemiologic evidence on early life factors associated with the subsequent diagnosis of endometriosis. In utero and early life exposures have previously been linked to a range of adult health outcomes, including infertility. SEARCH METHODS A systematic review of case–control, cross-sectional and cohort studies was conducted using the search terms ‘endometriosis’[MeSH] AND (‘risk factors’[MeSH] OR ‘protective factors’[MeSH]) AND (‘in utero’, ‘fetal’, ‘neonatal, ‘perinatal’, ‘developmental origins’, ‘early life’, ‘childhood’ OR ‘life course’) in Embase, PubMed and Scopus databases. The review included articles published in English until 10 June 2018 with original data from studies with diagnosed endometriosis. The quality of primary studies was evaluated using the Newcastle–Ottawa Scale by both authors independently. Due to the degree of inconsistency in the measurements and study methods, a qualitative assessment of findings was undertaken rather than meta-analysis. OUTCOMES The search retrieved 70 records without duplicates that contained 20 records on human case–control, cross-sectional or cohort studies, from which 11 papers/studies were selected based on their assessment score. The majority of studies found that women born with low birthweight (&amp;lt;2.5 kg or &amp;lt;5.5 lb) were more likely to be diagnosed with endometriosis. For other early life factors, the evidence is mixed or limited, with further research needed on the association of endometriosis with preterm birth, in utero exposure to diethylstilbestrol and to maternal smoking, passive smoking in early life, and infant formula feeding (compared with breastfeeding). WIDER IMPLICATIONS While the weight of evidence points to low birthweight as a risk factor for diagnosis of endometriosis, future research is warranted on this and other key early life exposures where the findings are mixed to provide more robust evidence and for insights on potential causal pathways. Such research, however, needs to address current methodological issues, such as the use of prospective data from large population-based studies, better diagnostic methods to confirm disease free status, more consistent definitions of variables and consideration of potential biological mechanisms to guide the analyses. The improvements will advance the future synthesis of evidence to support clinically relevant risk assessment for a more timely diagnosis and treatment of endometriosis.
WHO guidance on multidrug-resistant tuberculosis treatment: using and communicating the evidence
Authors: Dennis Falzon, Holger J. Schünemann, Matteo Zignol, Fuad Mirzayev, Tereza Kasaeva
Journal: European Respiratory Journal (2020)

From the authors :L. Guglielmetti and co-workers acknowledge that methods used by the World Health Organization (WHO) to develop guidance have improved policies on multidrug-resistant tuberculosis (MDR-TB) in recent years. However, they express some concerns about the interpretation and communication of evidence in the 2019 WHO consolidated guidelines for drug-resistant TB treatment [1]. WHO MDR-TB treatment guidelines detail how evidence and other considerations are used to develop recommendations <http://bit.ly/35qSrZT>