tbuckley/cabot-search huggingface dataset:
Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies
Authors: Sina Naghshi, Omid Sadeghi, Walter C Willett, Ahmad Esmaillzadeh
Journal: BMJ (2020)

Abstract Objective To examine and quantify the potential dose-response relation between intake of total, animal, and plant protein and the risk of mortality from all causes, cardiovascular disease, and cancer. Design Systematic review and meta-analysis of prospective cohort studies. Data sources PubMed, Scopus, and ISI Web of Science until December 2019, and references of retrieved relevant articles. Study selection Prospective cohort studies that reported the risk estimates for all cause, cardiovascular, and cancer mortality in adults aged 18 or older. Data synthesis Random effects models were used to calculate pooled effect sizes and 95% confidence intervals for the highest versus lowest categories of protein intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between protein intake and mortality. Results 32 prospective cohort studies were included in the systematic review and 31 in the meta-analysis. During the follow-up period of 3.5 to 32 years, 113 039 deaths (16 429‬ from cardiovascular disease and 22 303‬ from cancer) occurred among 715 128 participants. Intake of total protein was associated with a lower risk of all cause mortality (pooled effect size 0.94, 95% confidence interval 0.89 to 0.99, I 2 =58.4%, P&lt;0.001). Intake of plant protein was significantly associated with a lower risk of all cause mortality (pooled effect size 0.92, 95% confidence interval 0.87 to 0.97, I 2 =57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% confidence interval 0.80 to 0.96, I 2 =63.7%, P=0.001), but not with cancer mortality. Intake of total and animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality. A dose-response analysis showed a significant inverse dose-response association between intake of plant protein and all cause mortality (P=0.05 for non-linearity). An additional 3% energy from plant proteins a day was associated with a 5% lower risk of death from all causes. Conclusions Higher intake of total protein was associated with a lower risk of all cause mortality, and intake of plant protein was associated with a lower risk of all cause and cardiovascular disease mortality. Replacement of foods high in animal protein with plant protein sources could be associated with longevity.
Characteristics and Risk Factors of Post-Infection Irritable Bowel Syndrome After Campylobacter Enteritis
Authors: Antonio Berumen, Ryan Lennon, Margaret Breen-Lyles, Jayne Griffith, Robin Patel, David Boxrud, Marijke Decuir, Gianrico Farrugia, Kirk Smith, Madhusudan Grover
Journal: Clinical Gastroenterology and Hepatology (2020)
AB0764 SAFETY OF SYSTEMIC CORTICOSTEROIDS IN A SHORT REGIMEN IN PATIENTS WITH PSORIATIC ARTHRITIS. RETROSPECTIVE ANALYSIS OF A LARGE OBSERVATIONAL COHORT.
Authors: L. Farran Ortega, M. Tormo Ratera, J. Lluch Pons, M. Mora, C. Marco Pascual, X. González Giménez, J. M. Nolla, J. Rodríguez
Journal: Annals of the Rheumatic Diseases (2020)

Background: There is controversy surrounding the use of systemic corticosteroids in psoriatic arthritis (PsA). It’s an accepted fact that the use of systemic corticosteroids can trigger severe flare-up of erythroderma or pustular psoriasis. Nevertheless, corticosteroids have been used to achieve faster improvement of joint symptoms of PsA. Objectives: To analyze the use of systemic corticosteroids at intermediate doses in a short regimen in patients with PsA, as well as the serious complications of psoriasis upon withdrawal. Methods: Retrospective analysis of an observational cohort of 453 patients from a university hospital, following a specific protocol from 1992 to 2019. The following variables have been collected: corticosteroid treatment (methylprednisolone ≤16mg /day in a slow tapering regimen in 2 months), demographic and disease factors, comorbidities that could be associated (diabetes mellitus, high blood pressure, severe infections) and serious complications of psoriasis (erythroderma or pustular psoriasis). To assess the activity of psoriasis, physician global assessment is mostly used and occasionally to a lesser extent body surface area and psoriasis area severity index. Statistical analysis (SPSS v.25): descriptive analysis, Chi-squared test for qualitative variables and t-student test for quantitative variables. Results: In our series, 35.98% (163/453) of patients have received short corticosteroid regimen at some point in follow-up care, of which 93.8% received concomitant treatment with disease modifying antirheumatic drugs (DMARD). Only 6.2% of the patients who received short corticosteroid regimen presented a flare-up of psoriasis, most of them mildly. No patient developed an erythroderma or severe pustular psoriasis. After analyzing the data, a greater use of this regimen of treatment has been observed in patients with dactylitis (44.6% with dactylitis vs 27.8% without dactylitis, p&lt;0.001) and a lower use of corticosteroids in axial PsA (14% of axial PsA vs 41% of non-axial PsA, p&lt;0.001). There were no significant differences in the use of corticosteroids in respect to sex, age, age of onset of PsA, duration of PsA or high blood pressure. Nor in factors of poor radiographic prognosis: number of damaged joints, mutilating PsA and carpitis. Conclusion: In our series, no patient developed an erythroderma or severe pustular psoriasis and most of the flare-ups of psoriasis were mild. The use of systemic corticosteroids at intermediate doses in a slow tapering regimen concomitantly with DMARD can be safely used in patients with PsA. References: None Disclosure of Interests: None declared
Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?
Authors: Chandra B. Mishra, Manisha Tiwari, Claudiu T. Supuran
Journal: Medicinal Research Reviews (2020)

Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H+ ions and play a crucial role in regulating many physiological processes. CAs are well-studied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.
Covid-19: Former civil service head criticises government’s response to crisis
Authors: Shaun Griffin
Journal: BMJ (2020)

The former head of the British civil service has criticised the government’s response to the covid crisis, saying that it had been distorted by political expediency and disadvantaged by unbalanced advice.

Gus O’Donnell made the comments on 22 July when giving evidence to the House of Lords public services committee’s inquiry into how covid-19 has affected public services and the lessons to be learnt from the lockdown.

“The covid crisis started as a health crisis, but our response has massive economic implications. The problem is that we have SAGE [the Scientific Advisory Group for Emergencies] stuffed full of biomedical scientists and no economists,” he said, adding that a cost-benefit framework was the “biggest thing that was …
Abstract 15470: When a Boy Becomes a Man: Should Adult ICD Criteria Apply to Boys With Duchenne Muscular Dystrophy?
Authors: Naomi J Kertesz, Anna Kamp, W. R Thompson, Andreas S Barth, Ian Law, Sarosh P Batlivala, Nancy Halnon, Anne Fournier, Christopher Spurney, Madoka Mori-Yoshimura, Larry W Markham, Linda Cripe
Journal: Circulation (2017)

Introduction: With increases in survival by addressing pulmonary complications, cardiomyopathy is a leading cause of mortality in Becker/Duchenne Muscular Dystrophy (DMD). The current adult ICD gui...
THU0026 A single nucleotide polymorphism on the il-10 locus defines an expression polymorphism and a possible risk factor to develop ra
Authors: LR Lard, JJ Schonkeren, E Pieterman, R Westendorp, FC Breedveld, TW Huizinga
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> IL-10 production differs between individuals. We have evaluated the IL-10 production in whole blood cultures with/without LPS. The comparison of monozygotic twins, sibs and unrelated individuals yielded an estimate of heritability of 70%. The IL-10 production was associated with haplotypes defined by alleles of CA-repeats. In line with these results we have demonstrated that the interindividual differences in production of mRNA encoding IL-10 are similar than the interindividual differences in IL-10 protein production. <h3>Objectives</h3> To define SNPs associated with common haplotypes, to study the association of IL-10 production with haplotypes/SNPs and to measure the distribution of IL-10 SNPs in RA versus controls. <h3>Methods</h3> DNA of high and low IL10 producers were sequenced. Subsequently, the association between LPS-induced IL-10 production and previously described panel was analysed. <h3>Results</h3> The following SNPs were identified: -3575 A to G, -2849 A to G, -2763 A to C and -1330 A to G. Previously we have identified 4 ancestral IL-10 haplotypes. The current SNP?s on: IL10.1 R3-AAAA-(IL10G)-GCC, IL10.2 R2-TGCG-(IL10G)-ACC, IL10.3 R2-AGAA-(IL10G)-GCC, and IL10.4 R2-TGCC-(IL10G)-ATA. To investigate whether these SNP?s were functional we analysed the LPS-induced IL-10 production of 161 healthy donors with a specific genotype: -3575: AA (n = 38) 1896 ng/ml, AT (n = 76) 3232 ng/ml, TT (n = 47) 3195 ng/ml. -2849: AA (n = 21) 2115 ng/ml, AG (n = 75) 2950 ng/ml, GG (n = 65) 3111 ng/ml (MW-test both p &lt; 0.05). Next, the analysis was repeated in a different group of donors: 135 partners of patients with SLE/MS: -3575: AA (n = 29) 4190 ng/ml, AT (n = 71) 4521 ng/ml, TT (n = 35) 4401 ng/ml (MW-test P = 0.6). -2849: AA (n = 26) 3845 ng/ml, AG (n = 41) 4577 ng/ml, GG (n = 68) 4543 ng/ml (MW?test P = 0.04, for G carrier versus non G: P = 0.02). Next, the distribution of -2849 SNP was compared in RA patients compared to controls. Control-Panels were 1) partners of MS-SLE patients and 2) organ donors. RA-patients were: 1) incident RA cases, 2) outpatient consecutive RA and 3) RA patients from our early arthritis cohort. Control 1) AA 27, AG 42, GG 71; 2) AA 16, AG 64, GG 88; RA patients 1) AA 3, AG 38, GG 51; 2) AA 24, AG 141, GG 152; 3) AA 16, AG 74, GG 91. Total chi-square: P = 0.0014. <h3>Conclusion</h3> We have previously found that the allele IL-10R3 microsatellite was less frequent in three ethnic groups of RA patients (Afro-americans p &lt; 0.01, English p &lt; 0.008 and Scottish p &lt; 0.02). The SNP that defines the haplotype on which R3 is located is also less prevalent in three groups of dutch RA compared to two groups of dutch controls. These data suggest that a high innate IL-10 production is a risk factor for RA. This may be due to the B-cell stimulating properties of IL-10.
Abstract #3280: INrf2/Nrf2 control of Drug-Induced Apoptosis
Authors: Suryakant Niture, Anil Jaiswal
Journal: Cancer Research (2009)

INrf2:Nrf2 serve as sensor of chemical and radiation induced oxidative and electrophilic stress. Nrf2 is a nuclear transcription factor that regulates expression and coordinated induction of a battery of defensive genes including detoxifying enzymes and antioxidant genes. This induction is a mechanism of critical importance in neutralizing the stressors and providing cellular protection leading to cell survival. Nrf2 degrades predominantly within the cytoplasm of the cells by the interaction of actin-bound cytosolic protein, INrf2 (inhibitor of Nrf2) or Keap1 (Kelch-like ECH-associated protein 1). INrf2 functions as a substrate adaptor protein for a Cul3-Rbx1-dependent E3 ubiquitin ligase complex to ubiquitinate and degrade Nrf2 thus maintaining a steady-state levels of Nrf2. In the present study, we investigated the role of INrf2/Nrf2 on drug-induced apoptosis. Over expression of INrf2 increased and Nrf2 decreased Etoposide-induced apoptosis in tetracycline inducible human kidney carcinoma HEK293 cells. Immunoprecipitation assays revealed that INrf2 interacted with Nrf2 and also with PGAM5/Bcl-XL complex through interaction with PGAM5. Over expression of INrf2 led to ubiquitination and degradation of Nrf2 and down regulation of anti-apoptotic Bcl2 gene expression. Over expression of INrf2 also led to degradation of PGAM5/Bcl-XL complex. The down regulation of Bcl2 and degradation of Bcl-XL led to increase in Bax and apoptosis. Over expression of Nrf2 or treatment of cells with antioxidant led to increased nuclear localization of Nrf2 and resistance to Etoposide-mediated apoptosis. This is through Nrf2 activation of Bcl2 and Bcl-XL gene expression. Increase in Bcl2 and Bcl-XL led to decrease in Bax and reduced apoptosis. Deletion mapping and transfection assays identified the antioxidant response element (ARE) that mediated Nrf2 induction of Bcl2 and Bcl-XL. These results led to conclusion that INrf2 increases and Nrf2 decreases drug-induced apoptosis by manipulating Bcl-XL degradation and expression of Bcl2 and Bcl-XL.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3280.
The role of non-invasive ventilation in weaning and decannulating critically ill patients with tracheostomy: A narrative review of the literature
Authors: Miguel Guia, Laura D Ciobanu, Jithin K Sreedharan, Mohamed E. Abdelrahim, Gil Gonçalves, Bruno Cabrita, Jaber S. Alqahtani, Jun Duan, Mohamad El-Khatib, Montserrat Diaz-Abad, Jakob Wittenstein, Habib M.R. Karim, Pradipta Bhakta, Paolo Ruggeri, Giancarlo Garuti, Karen E.A. Burns, Guy W. Soo Hoo, Raffaele Scala, Antonio Esquinas
Journal: Pulmonology (2020)

Invasive mechanical ventilation (IMV) is associated with several complications. Placement of a long-term airway (tracheostomy) is also associated with short and long-term risks for patients. Nevertheless, tracheostomies are placed to help reduce the duration of IMV, facilitate weaning and eventually undergo successful decannulation. We performed a narrative review by searching PubMed, Embase and Medline databases to identify relevant citations using the search terms (with synonyms and closely related words) "non-invasive ventilation", "tracheostomy" and "weaning". We identified 13 publications comprising retrospective or prospective studies in which non-invasive ventilation (NIV) was one of the strategies used during weaning from IMV and/or tracheostomy decannulation. In some studies, patients with tracheostomies represented a subgroup of patients on IMV. Most of the studies involved patients with underlying cardiopulmonary comorbidities and conditions, and primarily involved specialized weaning centres. Not all studies provided data on decannulation, although those which did, report high success rates for weaning and decannulation when using NIV as an adjunct to weaning patient off ventilatory support. However, a significant percentage of patients still needed home NIV after discharge. The review supports a potential role for NIV in weaning patients with a tracheostomy either off the ventilator and/or with its decannulation. Additional research is needed to develop weaning protocols and better characterize the role of NIV during weaning.
Second Generation Tyrosine Kinase Inhibitors (2G-TKI) in the Frontline Treatment of Elderly Patients with Chronic Myeloid Leukemia
Authors: Fabio Stagno, Roberto Latagliata, Mario Annunziata, Elisabetta Abruzzese, Fausto Castagnetti, Alessandra Iurlo, Monica Bocchia, Monica Crugnola, Nicola Sgherza, Attilio Guarini, Federica Sorà, Isabella Capodanno, Carmen Fava, Antonella Gozzini, Massimiliano Bonifacio, Sabrina Crescenzi Leonetti, Sara Galimberti, Costanzo Feo, Enrico Montefusco, Mario Tiribelli, Patrizia Pregno, Micaela Bergamaschi, Manuela Rizzo, Agostino Antolino, Endri Mauro, Antonella Russo Rossi, Bruno Martino, Raffaele Palmieri, Maria Rosaria Esposito, Maria Iovine, Paolo Danise, Antonello Sica, Paolo Vigneri, Massimo Breccia, Gianantonio Rosti, Robin Foa, Luigiana Luciano
Journal: Blood (2017)
Multidrug resistant tuberculosis
Authors: J. Millard, C. Ugarte-Gil, D. A. J. Moore
Journal: BMJ (2015)

#### The bottom line

Tuberculosis remains a major cause of morbidity and mortality globally, with an estimated nine million people developing the disease and 1.5 million deaths in 2013; equating to 4100 deaths a day.1 Nevertheless, considerable gains have been made in international tuberculosis control; incidence rates are decreasing (albeit slowly) and mortality has been reduced by 45% worldwide. The advent of multidrug resistant tuberculosis threatens this progress. In this review we detail the challenges faced globally in the diagnosis, treatment, and control of multidrug resistant tuberculosis and why this matters to high and low burden multidrug resistant tuberculosis settings alike.

#### Sources and selection criteria

We searched Medline, Embase, and Scielo with the terms “MDR TB”, “Tuberculosis, Multidrug-Resistant”. We also reviewed the World Health Organization Global Tuberculosis Report 2014 and other national tuberculosis programme reports. We included data from systematic reviews/meta-analyses, randomised controlled trials, and good quality observational studies focused on multidrug resistant tuberculosis.

Rifampicin and isoniazid form the backbone of conventional first line treatment for tuberculosis. Multidrug …
Abstract 13806: Blood Pressure Response to an Isometric Contraction Predicts Left Ventricular Hypertrophy
Authors: Andreas Pittaras, Peter F Kokkinos, Michael Doumas, Immanuel Samuel, Haralampos Grassos, Manolis Kallistratos, Leonidas Poulimenos, Georgia Pyriovoli, Dimitrios Gourlis, Athanasios Manolis, Konstantinos Imprialos, Konstantinos Stavropoulos, Charles Faselis
Journal: Circulation (2019)

Introduction: Left ventricular hypertrophy (LVH) is associated with a significant increase cardiovascular events. LVH is independent of blood pressure (BP) and other confounders. However, the prese...
Sirtuin activation targets IDH-mutant tumors
Authors: Julie J Miller, Alexandria Fink, Jack A Banagis, Hiroaki Nagashima, Megha Subramanian, Christine K Lee, Lisa Melamed, Shilpa S Tummala, Kensuke Tateishi, Hiroaki Wakimoto, Daniel P Cahill
Journal: Neuro-Oncology (2020)

Isocitrate dehydrogenase (IDH)-mutant tumors exhibit an altered metabolic state and are critically dependent upon nicotinamide adenine dinucleotide (NAD+) for cellular survival. NAD+ steady-state levels can be influenced by both biosynthetic and consumptive processes. Here, we investigated activation of sirtuin (SIRT) enzymes, which consume NAD+ as a coenzyme, as a potential mechanism to reduce cellular NAD+ levels in these tumors.The effect of inhibition or activation of sirtuin activity, using (i) small molecules, (ii) clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 gene editing, and (iii) inducible overexpression, was investigated in IDH-mutant tumor lines, including patient-derived IDH-mutant glioma lines.We found that Sirt1 activation led to marked augmentation of NAD+ depletion and accentuation of cytotoxicity when combined with inhibition of nicotinamide phosphoribosyltransferase (NAMPT), consistent with the enzymatic activity of SIRT1 as a primary cellular NAD+ consumer in IDH-mutant cells. Activation of Sirt1 through either genetic overexpression or pharmacologic Sirt1-activating compounds (STACs), an existing class of well-tolerated drugs, led to inhibition of IDH1-mutant tumor cell growth.Activation of Sirt1 can selectively target IDH-mutant tumors. These findings indicate that relatively nontoxic STACs, administered either alone or in combination with NAMPT inhibition, could alter the growth trajectory of IDH-mutant gliomas while minimizing toxicity associated with cytotoxic chemotherapeutic regimens.
Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity
Authors: Lucy Wanjiru Njunge, Andreanne Poppy Estania, Yao Guo, Wanqian Liu, Li Yang
Journal: Theranostics (2020)

Over the years, tumor progression locus 2 (TPL2) has been identified as an essential modulator of immune responses that conveys inflammatory signals to downstream effectors, subsequently modulating the generation and function of inflammatory cells. TPL2 is also differentially expressed and activated in several cancers, where it is associated with increased inflammation, malignant transformation, angiogenesis, metastasis, poor prognosis and therapy resistance. However, the relationship between TPL2-driven inflammation, tumorigenesis and tumor immunity has not been addressed. Here, we reconcile the function of TPL2-driven inflammation to oncogenic functions such as inflammation, proliferation, apoptosis resistance, angiogenesis, metastasis, immunosuppression and immune evasion. We also address the controversies reported on TPL2 function in tumor-promoting inflammation and tumorigenesis, and highlight the potential role of the TPL2 adaptor function in regulating the mechanisms leading to pro-tumorigenic inflammation and tumor progression. We discuss the therapeutic implications and limitations of targeting TPL2 for cancer treatment. The ideas presented here provide some new insight into cancer pathophysiology that might contribute to the development of more integrative and specific anti-inflammatory and anti-cancer therapeutics.
Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase
Authors: Rosario Pivonello, Maria Fleseriu, John Newell-Price, Xavier Bertagna, James Findling, Akira Shimatsu, Feng Gu, Richard Auchus, Rattana Leelawattana, Eun Jig Lee, Jung Hee Kim, André Lacroix, Audrey Laplanche, Paul O'Connell, Libuse Tauchmanova, Alberto M Pedroncelli, Beverly M K Biller
Journal: The Lancet Diabetes & Endocrinology (2020)