tbuckley/cabot-search huggingface dataset:
How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence
Authors: Damian Best, Alison Avenell, Siladitya Bhattacharya
Journal: Human Reproduction Update (2017)

The prevalence of obesity is increasing worldwide, with a corresponding increase in overweight and obese patients referred with infertility. This systematic review aimed to determine whether non-surgical weight reduction strategies result in an improvement in reproductive parameters affected by obesity, e.g. delayed time to pregnancy, oligozoospermia and azoospermia. No prior reviews have examined this within the general fertility population, or in both sexes.Our objective was to answer the question: 'In overweight and obese women, men and couples seeking fertility treatment, what non-surgical weight-loss interventions have been used, and how effective are they at weight loss and improving reproductive outcomes?'An electronic search of MEDLINE, EMBASE and the Cochrane Library was performed for studies between January 1966 and March 2016. Text word and MESH search terms used related to infertility, weight and barriers to weight loss. Inclusion criteria were an intervention to change lifestyle evaluated in any study design in participants of either gender with an unfulfilled desire to conceive. Studies were excluded if they included participants not attempting pregnancy, with illnesses that might cause weight fluctuations, or studies evaluating bariatric surgery. Two reviewers performed data extraction and quality assessment using the Cochrane Risk of Bias Tool for randomized trials, and a ratified checklist (ReBIP) for non-randomized studies.A total of 40 studies were included, of which 14 were randomised control trials. Primary outcomes were pregnancy, live birth rate and weight change. In women, reduced calorie diets and exercise interventions were more likely than control interventions to result in pregnancy [risk ratio 1.59, 95% CI (1.01, 2.50)], and interventions resulted in weight loss and ovulation improvement, where reported. Miscarriage rates were not reduced by any intervention.Overweight and obese persons seeking fertility should be educated on the detrimental effects of fatness and the benefits of weight reduction, including improvement in pregnancy rates. A combination of a reduced calorie diet, by reducing fat and refined carbohydrate intake, and increased aerobic exercise should form the basis of programmes designed for such individuals. A lack of randomized studies in men and couples, and studies evaluating barriers to undertaking weight loss in infertile populations is evident, and future research should examine these issues further.
Abstract 51: Thymosin β4 Targets Wisp1 to Protect Cardiomyocytes in AngII- induced Cardiac Hypertrophy
Authors: Sudhiranjan Gupta, Li Li, Rakesh Guleria, Kenneth M Baker
Journal: Circulation Research (2015)

Background: Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocytes hypertrophy is currently unknown. The purpose of this study is to dissect the cardio-protective mechanism of Tβ4 in Ang II induced cardiac hypertrophy. Methods: Rat neonatal cardiomyocytes with or without Tβ4 pretreatment were stimulated with Ang II and expression of cell sizes, hypertrophy marker genes and Wnt signaling components was evaluated by quantitative real-time PCR, western blotting and fluorescent microscopy. Selected target gene Wisp-1 was either overexpressed or silenced by siRNA transfections in neonatal cardiomyocytes and effect of Tβ4 in Ang II-induced cardiac hypertrophy was evaluated. Results: Pre-treatment of Tβ4 resulted in reduction of cell sizes, hypertrophy marker genes and WNT-associated gene expression and levels induced by Ang II in cardiomyocytes. Tβ4 pretreatment also resulted in an increase in the expression of antiapoptotic proteins and reduction of Bax/BCl 2 ratio in the cardiomyocytes. Wisp-1 overexpression promotes cardiac hypertrophy and was reversed by pretreatment with Tβ4. Knocking down of Wisp1 partly rescue the cells from hypertrophic response after Tβ4 treatment. Conclusion: This is the first report that demonstrates the effect of Tβ4 on cardiomyocytes hypertrophy and its capability to selectively target Wisp-1 in neonatal cardiomyocytes thus preventing cell death, thereby, protecting the myocardium. Wisp-1 promotes the cardiac hypertrophy which was prevented by Tβ4 treatment.
THU0266 Damage indexes in patients with systemic lupus erythematosus and secondary antiphospholipid syndrome: diaps vs slicc/acr damage index
Authors: D Potarniche, D Mazilu, I Saulescu, A Borangiu, L Groseanu, C Constantinescu, V Vlad, F Berghea, V Bojinca, D Opris-Belinski, A Balanescu, D Predeteanu, R Ionescu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are systemic autoimmune diseases that have overlaping irreversible organ damages. Since SLICC/ACR Damage Index (SDI) misses key features of APS, the Damage Index in patients with Thrombotic Antiphospholipid Syndrome (DIAPS) was proposed. <h3>Objectives</h3> To assess the differences in indexes available for measuring organ damage in a cohort of patients with SLE and secondary APS. <h3>Methods</h3> Clinical records of patients with SLE and secondary APS were reviewed. Data on medical history and clinical manifestations were collected. The two damage indexes, SDI and DIAPS, were applied. Comparison between the two indexes was done for each organ system affected. <h3>Results</h3> Sixty five clinical charts were reviewed, 5 had been excluded for incomplete information. SDI and DIAPS was recorded in 60 patients. Patient9s mean age was 45.05±14.61 years, with mean disease duration of 9.47±6.96 years. Mean SDI in our cohort was 4,15±2.58 and mean DIAPS – 4.08±3.41. SDI correlated significant to DIAPS (R=0.826, p&lt;0.000). Neuropsyhiatric manifestations were found in 25 patients (41.7%). Their mean SDI value was 4.92±2.73 and DIAPS value of 5.52±3.47. DIAPS value was higher in the subgroup of patients with neuropsyhiatric (p=0.006) and respiratory system damage (p=0.037). This difference was not observed regarding SDI value. DIAPS value correlated significantly to neurological (R=0.397, p=0.002) and pulmonary damage (R=0.364, p=0.004), but not to SDI value. No diferrences were observed between the two scores regarding perypheral vascular manifestation (DIAPS p=0.221, SDI p=0.136) and renal involvement (DIAPS p=0.062, SDI p=0.078). <h3>Conclusions</h3> SDI may underestimate APS related damage in patients with SLE and secondary regarding neurological and pulmonary organ involvement. Given the implications for high morbidity and mortality, DIAPS may be the appropriate damage score to be used. <h3>References</h3> P. Alba et al. Organ Damage and Quality of Life in Antiphospholipid Syndrome. Current Rheumatology Reports. February 2016, 18:7. Barbhaiya et al. Utility of the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index for Antiphospholipid Antibody (aPL) Positive Patients. [abstract]. Arthritis Rheum 2011;63 Suppl 10:7. <h3>Disclosure of Interest</h3> None declared
Biochemical Surrogate Markers of Hemolysis Do Not Correlate with Directly Measured Erythrocyte Survival in Sickle Cell Anemia
Authors: Charles T. Quinn, Eric P. Smith, Shahriar Arbabi, Paramjit Khera, Christopher J. Lindsell, Omar Niss, Clinton H Joiner, Robert S. Franco, Robert M. Cohen
Journal: Blood (2016)
Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development
Authors: Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S. Shivatare, Bryan Briney, James E. Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R. Burton
Journal: Immunity (2017)
AB0413 Induction and progression of subcutaneous nodulosis in rheumatoid arthritis patients treated with tocilizumab
Authors: R Talotta, A Batticciotto, MC Ditto, MC Gerardi, D Ventura, P Sarzi Puttini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tocilizumab (TCZ) is a monoclonal antibody (moAb) directed against the IL-6 receptor approved for moderate-to severe rheumatoid arthritis (RA) treatment. Some authors have reported a beneficial effect of TCZ in preventing lung and subcutaneous nodulosis in RA patients. On the contrary, to our knowledge no data concerning the acceleration of subcutaneous nodulosis under TCZ therapy are currently available. <h3>Objectives</h3> We report a small case series of 5 RA patients experimenting an evident worsening of subcutaneous nodulosis during the treatment with intravenous tocilizumab. <h3>Methods</h3> Our cohort included 5 patients (1 male and 4 females, mean age ± Standard Deviation (SD) 64±10.6 years, mean disease duration ± SD 21.8±10.9 years). Four patients were rheumatoid factor and anti-citrullinated peptide antibodies positive. Each patient had been previously treated with several conventional and biologic drugs. At the time of observation, three subjects were practicing methotrexate (MTX), two patients were taking hydroxychloroquine (HCQ) and one patient was taking prednisone. Intravenous tocilizumab 8 mg/kg every 4 weeks was administered for a mean ± SD of 43.4±32.4 months, with a good disease control in 3 cases. All the patients had a previous history of subcutaneous nodulosis that considerably worsened during the treatment with tocilizumab. Patients experimented the development of new subcutaneous nodules localized at the fingers, elbows or the inframammary fold, tending to ulceration. The management of this medical event included the tapering of MTX, the administration of steroids, the addition of HCQ, the use of antibiotics and surgery. However, neither pharmacological nor surgical treatment was completely effective, as nodules tended to recur and to increase in number and dimensions. <h3>Results</h3> To our knowledge this is the first report describing an accelerated subcutaneous nodulosis in a small cohort of RA patients treated with tocilizumab. <h3>Disclosure of Interest</h3> None declared
Nanochip Turns Skin Into a Bioreactor
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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A Recombinant Fragment of Human Surfactant Protein D Suppresses Basophil Activation and T-Helper Type 2 and B-Cell Responses in Grass Pollen–induced Allergic Inflammation
Authors: Asif S. Qaseem, Iesha Singh, Ansar A. Pathan, Janice A. Layhadi, Rebecca Parkin, Fedina Alexandra, Stephen R. Durham, Uday Kishore, Mohamed H. Shamji
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Recombinant fragment of human surfactant protein D (rfhSP-D) has been shown to suppress house dust mite– and Aspergillus fumigatus–induced allergic inflammation in murine models.Objectives: We sought to elucidate the effect of rfhSP-D on high-affinity IgE receptor– and CD23-mediated, grass pollen–induced allergic inflammatory responses.Methods: rfhSP-D, containing homotrimeric neck and lectin domains, was expressed in Escherichia coli BL21(λDE3)pLysS cells. Peripheral blood mononuclear cells and sera were obtained from individuals with grass pollen allergy (n = 27). The effect of rfhSP-D on basophil activation and histamine release was measured by flow cytometry. IgE-facilitated allergen binding and presentation were assessed by flow cytometry. T-helper cell type 2 (Th2) cytokines were measured in cell culture supernatants. The effect of rfhSP-D on IgE production by B cells when stimulated with CD40L, IL-4, and IL-21 was also determined.Measurements and Main Results: rfhSP-D bound to Phleum pratense in a dose- and calcium-dependent manner. Allergen-induced basophil responsiveness and histamine release were inhibited in the presence of rfhSP-D, as measured by CD63, CD203c (P = 0.0086, P = 0.04205), and intracellularly labeled diamine oxidase (P = 0.0003, P = 0.0148). The binding of allergen–IgE complexes to B cells was reduced by 51% (P = 0.002) in the presence of rfhSP-D. This decrease was concomitant with reduction in CD23 expression on B cells (P < 0.001). rfhSP-D suppressed allergen-driven CD27−CD4+CRTh2+ T-cell proliferation (P < 0.01), IL-4, and IL-5 levels (all P < 0.01). Moreover, rfhSP-D inhibited CD40L/IL-4– and IL-21–mediated IgE production (77.12%; P = 0.02) by B cells.Conclusions: For the first time, to our knowledge, we show that rfhSP-D inhibited allergen-induced basophil responses at a single-cell level and suppressed CD23-mediated facilitated allergen presentation and Th2 cytokine production. In addition, rfhSP-D inhibited IgE synthesis by B cells, which is also a novel observation.
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor–Modified T Cells Engineered to Secrete Checkpoint Inhibitors
Authors: Si Li, Natnaree Siriwon, Xiaoyang Zhang, Shuai Yang, Tao Jin, Feng He, Yu Jeong Kim, John Mac, Zhengfei Lu, Sijie Wang, Xiaolu Han, Pin Wang
Journal: Clinical Cancer Research (2017)

Purpose: Despite favorable responses of chimeric antigen receptor (CAR)-engineered T-cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR T cells secreting checkpoint inhibitors (CPI) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model.Experimental Design: To evaluate the effector function and expansion capacity of CAR.αPD1-T cells in vitro, we measured the production of IFNγ and T-cell proliferation following antigen-specific stimulation. Furthermore, the antitumor efficacy of CAR.αPD1-T cells, CAR T cells, and CAR T cells combined with anti-PD-1 antibody was determined using a xenograft mouse model. Finally, the underlying mechanism was investigated by analyzing the expansion and functional capacity of TILs.Results: Human anti-PD-1 CPIs secreted by CAR.αPD1-T cells efficiently bound to PD-1 and reversed the inhibitory effect of PD-1/PD-L1 interaction on T-cell function. PD-1 blockade by continuously secreted anti-PD-1 attenuated the inhibitory T-cell signaling and enhanced T-cell expansion and effector function both in vitro and in vivo In the xenograft mouse model, we demonstrated that the secretion of anti-PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival.Conclusions: With constitutive anti-PD-1 secretion, CAR.αPD1-T cells are more functional and expandable, and more efficient at tumor eradication than parental CAR T cells. Collectively, our study presents an important and novel strategy that enables CAR T cells to achieve better antitumor immunity, especially in the treatment of solid tumors. Clin Cancer Res; 23(22); 6982-92. ©2017 AACR.
Abstract 289: Transcriptomic Analysis of Inter- and Intra-patient Variation in Human iPSCs: Platform for Precision Medicine to Predict Drug Toxicity
Authors: Elena Matsa, Paul W Burridge, Kun-Hsing Yu, Haodi Wu, Vittavat Termglinchan, Chun Liu, Praveen Shukla, Nazish Sayed, Ioannis Karakikes, Michael P Snyder, Joseph C Wu
Journal: Circulation Research (2016)

Rapid improvements in human induced pluripotent stem cell (hiPSC) differentiation methodologies have allowed previously unattainable access to high-purity, patient-specific cardiomyocytes (CMs) for use in disease modeling, cardiac regeneration, and drug testing. In the present study, we investigate the ability of hiPSC-derived cardiomyocytes (hiPSC-CMs) to reflect the donor’s genetic identity and serve as preclinical functional readout platforms for precision medicine. We used footprint-free Sendai virus to create two separate hiPSC clones from the fibroblasts of five different individuals lacking known mutations associated with cardiovascular disease. Whole genome expression profiling of hiPSC-CMs showed that inter-patient variation was greater than intra-patient variation, thereby verifying that reprogramming and cardiac differentiation technologies can preserve patient-specific gene expression signatures. Gene ontologies (GOs) accounting for inter-patient variation were mostly metabolic or epigenetic. Toxicology analysis based on gene expression profiles predicted patient-specific susceptibility of hiPSC-CMs to cardiotoxicity, and functional assays using drugs targeting key regulators in pathways predicted to produce cardiotoxicity showed inter-patient differential responses in hiPSC-CMs. Our data suggest that hiPSC-CMs can be used in vitro to predict and help prevent patient-specific drug-induced cardiotoxicity, potentially enabling personalized patient consultation in the future.
AB0303 Does comorbidity adversely impact on treatment response in patients with rheumatoid arthritis
Authors: CD Hughes, N Gullick
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The burden of comorbid illness in Rheumatoid Arthritis is high. Whilst there can be coincidental existence of comorbidity, it can be attributed to the disease process itself or therapeutic agents. Recent EULAR guidelines recommend reporting, screening and prevention of six common co-morbidities (cardiovascular, malignancy, infections, gastrointestinal, osteoporosis, depression). Limited research is available evaluating the impact of comorbidity on disease response following biologic treatment. <h3>Objectives</h3> To analyse retrospective data from the King9s College Hospital (KCH) Virtual Biologic Clinic (VBC) to assess the impact of comorbidity on disease response following treatment with biologics. <h3>Methods</h3> Retrospective patient note review data was collected for patients referred to the VBC from May 2013 to July 2016. The following data was recorded: age, sex, disease duration, smoking status, BMI, presence or absence of Anti CCP antibody +/-Rheumatoid factor and the six specified comorbidities. Disease Activity Score in 28 joints (DAS28) at time of referral for biologic and within 6 months of commencing treatment was also recorded in order to calculate treatment response. The impact of comorbidity and disease variables on 6 month EULAR response were analysed using logistic regression (SPSS version 23). <h3>Results</h3> The database contained 150 patients. 18 patients were excluded due to no follow-up DAS28, leaving 132 for analysis. Mean age and disease duration were 58 years and 10.45 years respectively. Comorbidity was present in 70% of patients. 70% of patients achieved a EULAR moderate response (improvement of &gt;1.2 of DAS28) and 36% of this group achieved EULAR good response (DAS28&lt;3.2). The most prevalent comorbidities were infection, cardiovascular disease and depression. Logistic regression analysis was run analysing EULAR moderate response against presence of comorbidity and dataset variables (age, gender, serostatus, baseline DAS, HAQ and polypharmacy). The resulting model was not statistically significant (p=0.975). Logistic regression analysis looking at EULAR good response against presence of comorbidity was also not statistically significiant (p=0.149). Analysis looking at EULAR good response against three variables (HAQ, baseline DAS and serostatus) was found to be statistically significant (p&lt;0.001) <h3>Conclusions</h3> Comorbidities were present in the majority of patients assessed (70%). Results show no significant relationship between EULAR moderate response or EULAR good response and the presence of comorbidity. Lower HAQ, lower baseline DAS28 and seronegativity contribute towards good treatment response.The limitations of this study include gaps in clinical records, absence of patient reported questionnaires, and small size of database. <h3>Disclosure of Interest</h3> None declared
AB0868 Is it appropriate to discontinue colchicine therapy in gout patients in remission?
Authors: Y İnan Özdem, N Kanıtez Alpay, S Çelik, S Öner Yılmaz, C Bes
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Colchicine can reduce the risk of recurrent attacks and it is an appropriate first-line gout attack prophylaxis therapy. There is limited data in the literature about duration of colchicine treatment in patients with gout disease. <h3>Objectives</h3> In this study, we aimed to investigate the frequency of gout attacks between patients with colchicine treatment and patients who are colchicine terminated. <h3>Methods</h3> 54 gout patients under colchicine treatment were enrolled to the study. The subjects were divided into 2 groups. Group 1 (n=19) was consisted of patients whom colchicine therapy was terminated because of remission for three months; group 2 (n=35) was consisted of patients on colchicine treatment. Groups were compared according to the existing of newly gout attacks after the 3rd month. Baseline and the third months of the uric acid levels were also analyzed in each group. <h3>Results</h3> The body mass indexes, the disease intervals, the number of the attacks, and the duration of the attacks were not significantly different (p&gt;0.05 for all) (Table 1). Compared to the group 2, the newly gout attacks were not found to be different in group 1 for 3 months (p&gt;0.05) (Table 1). The uric acid levels were significantly decreased both in two groups (both p&lt;0.05) (Table 2). <h3>Conclusions</h3> The colchicine is the mainstay treatment for gout disease. It not only prevents the attacks of the gouts also prevents the development of uric acid nephropathy that exaggerates the kidney disease in gout patients. This study showed that, in gout patients in remission, termination of the colchicine treatment does not affect the development of the new attacks as shown similar attacks were also observed in non-terminated patients. <h3>Disclosure of Interest</h3> None declared