tbuckley/cabot-search huggingface dataset:
Vitamin D supplementation in pregnancy and early infancy in relation to gut microbiota composition and <i>C. difficile</i> colonization: implications for viral respiratory infections
Authors: Kelsea M. Drall, Catherine J. Field, Andrea M. Haqq, Russell J. de Souza, Hein M. Tun, Nadia P. Morales-Lizcano, Theodore B. Konya, David S. Guttman, Meghan B. Azad, Allan B. Becker, Diana L. Lefebvre, Piush J. Mandhane, Theo J. Moraes, Malcolm R. Sears, Stuart E. Turvey, Padmaja Subbarao, James A. Scott, Anita L Kozyrskyj
Journal: Gut Microbes (2020)

In Canada and the US, the infant diet is supplemented with vitamin D via supplement drops or formula. Pregnant and nursing mothers often take vitamin D supplements. Since little is known about the impact of this supplementation on infant gut microbiota, we undertook a study to determine the association between maternal and infant vitamin D supplementation, infant gut microbiota composition and Clostridioides difficile colonization in 1,157 mother-infant pairs of the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study over 2009–2012. Logistic and MaAsLin regression were employed to assess associations between vitamin D supplementation, and C. difficile colonization, or other gut microbiota, respectively. Sixty-five percent of infants received a vitamin D supplement. Among all infants, infant vitamin D supplementation was associated with a lower abundance of genus Megamonas (q = 0.01) in gut microbiota. Among those exclusively breastfed, maternal prenatal supplementation was associated with lower abundance of Bilophila (q = 0.01) and of Lachnospiraceae (q = 0.02) but higher abundance of Haemophilus (q = 0.02). There were no differences in microbiota composition with vitamin D supplementation among partially and not breastfed infants. Neither infant nor maternal vitamin D supplementation were associated with C. difficile colonization, after adjusting for breastfeeding status and other factors. However, maternal consumption of vitamin-D fortified milk reduced the likelihood of C. difficile colonization in infants (adjustedOR: 0.40, 95% CI: 0.19–0.82). The impact of this compositional difference on later childhood health, especially defense against viral respiratory infection, may go beyond the expected effects of vitamin D supplements and remains to be ascertained.
Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control
Authors: Franziska S Rathjens, Alica Blenkle, Lavanya M Iyer, Anke Renger, Fahima Syeda, Claudia Noack, Andreas Jungmann, Matthias Dewenter, Karl Toischer, Ali El-Armouche, Oliver J Müller, Larissa Fabritz, Wolfram-Hubertus Zimmermann, Laura C Zelarayan, Maria-Patapia Zafeiriou
Journal: Cardiovascular Research (2020)

Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias.
West Nile virus in humans, Greece, 2018: the largest seasonal number of cases, 9 years after its emergence in the country
Authors: Danai Pervanidou, Annita Vakali, Theano Georgakopoulou, Takis Panagiotopoulos, Eleni Patsoula, George Koliopoulos, Constantina Politis, Kostas Stamoulis, Elpida Gavana, Styliani Pappa, Maria Mavrouli, Maria Emmanouil, George Sourvinos, Andreas Mentis, Athanassios Tsakris, Christos Hadjichristodoulou, Sotirios Tsiodras, Anna Papa
Journal: Eurosurveillance (2020)

BackgroundHuman cases of West Nile virus (WNV) infection are recorded since 2010 in Greece, with seasonal outbreaks occurring almost annually. Enhanced surveillance has been implemented since 2010, to promptly characterise cases' temporal and geographical distribution and inform authorities for implementation of appropriate measures (mosquito control, health education, blood safety).AimWe describe the epidemiology of WNV human infections in Greece focusing on the 2018 season.MethodsThe National Public Health Organization advised physicians to test all suspect WNV infection cases and refer samples to reference laboratories. Laboratories notified diagnosed cases on a daily basis. Treating physicians, patients, and infected blood donors were interviewed within 48 hours after diagnosis and the probable infection location was identified. Hospitalised cases were followed up until discharge.ResultsA total of 317 autochthonous WNV infection cases were diagnosed in 2018. Among them, 243 cases had neuroinvasive disease (WNND), representing a 23% increase of WNND cases compared with 2010, the previous most intense season. There were 51 deaths. Cases started occurring from week 22, earlier than usual. Both rural and urban areas were affected, with 86 (26% of the total) municipalities belonging to seven (54% of the total) regions recording cases. Two major epicentres were identified in Attica and Central Macedonia regions.ConclusionsThe largest number of human cases of WNV infection ever recorded in Greece occurred in 2018, with a wide geographical distribution, suggesting intense virus circulation. Enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.
Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial
Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James C. H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Maria Rosario García Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander Spira, Scott N. Gettinger, Marcello Tiseo, Huamao M. Lin, Neeraj Gupta, Michael J. Hanley, Quanhong Ni, Pingkuan Zhang, Sanjay Popat
Journal: Journal of Clinical Oncology (2020)

Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events).Patients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected.Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69).Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.
Disparities in Cancer Outcomes Due to COVID-19—A Tale of 2 Cities
Authors: Onyinye D. Balogun, Vivian J. Bea, Erica Phillips
Journal: JAMA Oncology (2020)

A Tale of 2 CitiesThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the disease coronavirus 2019 (COVID-19), has ravaged the United States since the first case was documented in Washington State in January 2020.By early March, the first case of COVID-19 was confirmed in New York.From the very first case to present day, it has become increasingly clear that densely populated cities bear the brunt of this disease.In New York City as of July 7, 2020, approximately 214 000 cases and 18 000 deaths have been documented.While COVID-19 has had a worldwide impact, suspicions about its disproportionate effects on minority populations have now been confirmed with the release of data stratified by race and ethnicity.Within New York, we are witnessing 2 distinct trajectories and risk groups defined along the lines of race and socioeconomic status.As of July 7, 2020, the age-adjusted death rate for Hispanic and Black patients is twice that of White patients. 1Additionally, the Bronx, Queens, and Brooklyn each have twice the number of cases per 100 000 individuals as Manhattan and 3 to 4 times the number of cases as Staten Island.The reasons for these disparities have been discussed at length and include rates of preexisting comorbidities, a majority of the population employed in essential bluecollar jobs, living conditions, health literacy, and access to health care. 2 The impact of these changes on already wellestablished cancer care disparities is unknown but potentially devastating.At this time, oncologists have had to make difficult decisions weighing the benefits of treatment against the risks of COVID-19 infection and the increased risk of death among patients with cancer.Surgeries have been postponed, and chemotherapy and radiotherapy regimens have been delayed or altered to expedite treatment and minimize risk of exposure to coronavirus.It remains unclear the extent to which active or prior cancer diagnosis influences one's risk of COVID-19 infection.In a study of 1099 Chinese patients, cancer patients comprised 1% of COVID-19 cases.However, in initial reports from New York City, patients with cancer represent 6% of COVID-19 cases and 8% to 9% of those deemed critically ill or requiring mechanical ventilation.Moreover, patients with non-small cell lung cancer comprised more than half of COVID-19 cancer cases, suggesting differing susceptibilities based on the primary disease. 3ationwide, the breast cancer mortality rate is 40% higher for Black patients compared with White patients.In New York City, this inequity has worsened over time, increasing from 19% to 27% between 2005 to 2014.Similarly, the cervical cancer mortality rate is 23% higher for Hispanic women and 71% higher for Black women as well as for those residing in poorer neighbor-
AB0014 Tumour necrosis factor-alpha in patients with systemic lupus erythematosus
Authors: AG Borodin, AA Baranov, EL Nassonov, NG Klukvina
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> <h3>Methods</h3> To obtain information about the involvement of tumour necrosis factor-alpha (TNF-a) in the pathophysiology of SLE this cytokine was measured, by an enzyme linked immunosorbent assay, in sera from 109 patients (pts) with systemic lupus erythematosus (SLE) (44 men and 65 women). The results were compared with 20 healthy subjects. The mean level of TNF-alpha was 84,4+ 43,2 pg/ml in males (0–859 pg/ml) and 11+7,4 pg/ml in females (0–192,2 pg/ml). The difference between male and female cohorts was significant (p &lt; 0,002). The mean level of TNF-alpha was 0,6+0,8 (0–8,5 pg/ml) in donors. Patients of both groups (males and females) had a significantly higher serum TNF-alpha than control subjects (p &lt; 0,001). <h3>Results</h3> TNF-alpha was found positive (more than 3s.d. above the mean in normal controls) in 17 females (26%), 36 males (81,8%) in pts with SLE compared to 1 person (5%) of normal controls (p &lt; 0,05). Data differed statistically between patients in male and female groups and controls. The raised level of TNF-alpha was defined as low, moderate and high positive. We have found the low-positive TNF-alpha in 2 pts (3%), the moderate-positive in 8 pts (12%) and the high-positive in 7 pts (10%) in females. We found significant positive correlation between TNF-alpha and ESR (p &lt; 0,02), arthritis (p &lt; 0,01), capillaritis (p &lt; 0,01), lymphadenopathy (p &lt; 0,001); the negative correlation was observed with serum albumin (p &lt; 0,02) in females. The level of TNF-alpha was the low-positive in 2 pts (4,5%), the moderate-positive in 8 pts (18,1%), the high-positive in 26 pts (59%) in males. There was a positive correlation between TNF-alpha and SLAM index (p &lt; 0,01), SLEDAI (p &lt; 0,06), antiphospholipid syndrome (p &lt; 0,01), IgG-anticardiolipin antibodies (p &lt; 0,03) in male group. <h3>Conclusion</h3> There are differences between the level, the clinical value of TNF-alpha in male and female cohorts of pts with SLE. The measurement of TNF-alpha maybe a useful tool for monitoring disease activity, in the male cohort especially.
The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation
Authors: Alexander Hooftman, Stefano Angiari, Svenja Hester, Sarah E. Corcoran, Marah C. Runtsch, Chris Ling, Melanie C. Ruzek, Peter F. Slivka, Anne F. McGettrick, Kathy Banahan, Mark M. Hughes, Alan D. Irvine, Roman Fischer, Luke A.J. O’Neill
Journal: Cell Metabolism (2020)
Guiding Clinical Decisions Through Predictive Risk Rules
Authors: Benjamin A. Goldstein, Armando D. Bedoya
Journal: JAMA Network Open (2020)

Matthew M. Churpek, MD, MPH, PhD; Kyle A. Carey, MPH; Dana P. Edelson, MD, MS; Tripti Singh, MBBS; Brad C. Astor, PhD; Emily R. Gilbert, MD; Christopher Winslow, MD; Nirav Shah, MD, MPH; Majid Afshar, MD, MSCR; Jay L. Koyner, MD
Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study
Authors: Nicklas Vinter, Qiuxi Huang, Morten Fenger-Grøn, Lars Frost, Emelia J Benjamin, Ludovic Trinquart
Journal: BMJ (2020)

Abstract Objective To assess temporal trends in the association between newly diagnosed atrial fibrillation and death. Design Community based cohort study. Setting Framingham Heart Study cohort, in 1972-85, 1986-2000, and 2001-15 (periods 1-3, respectively), in Framingham, MA, USA. Participants Participants with no atrial fibrillation, aged 45-95 in each time period, and identified with newly diagnosed atrial fibrillation (or atrial flutter) during each time period. Main outcome measures The main outcome was all cause mortality. Hazard ratios for the association between time varying atrial fibrillation and all cause mortality were calculated with adjustment for time varying confounding factors. The difference in restricted mean survival times, adjusted for confounders, between participants with atrial fibrillation and matched referents at 10 years after a diagnosis of atrial fibrillation was estimated. Meta-regression was used to test for linear trends in hazard ratios and restricted mean survival times over the different time periods. Results 5671 participants were selected in time period 1, 6177 in period 2, and 6174 in period 3. Adjusted hazard ratios for all cause mortality between participants with and without atrial fibrillation were 1.9 (95% confidence interval 1.7 to 2.2) in time period 1, 1.4 (1.3 to 1.6) in period 2, and 1.7 (1.5 to 2.0) in period 3 (P trend =0.70). Ten years after diagnosis of atrial fibrillation, the adjusted difference in restricted mean survival times between participants with atrial fibrillation and matched referents decreased by 31%, from −2.9 years (95% confidence interval −3.2 to −2.5) in period 1, to −2.1 years (−2.4 to −1.8) in period 2, to −2.0 years (−2.3 to −1.7) in period 3 (P trend =0.03). Conclusions No evidence of a temporal trend in hazard ratios for the association between atrial fibrillation and all cause mortality was found. The mean number of life years lost to atrial fibrillation at 10 years had improved significantly, but a two year gap compared with individuals without atrial fibrillation still remained.
<i>Notes from the Field:</i> Multidrug-Resistant Tuberculosis Among Workers at Two Food Processing Facilities — Ohio, 2018–2019
Authors: Amish Talwar, Rebekah Stewart, Sandy P. Althomsons, Jessica Rinsky, David A. Jackson, Maria E. Galvis, Philip Graham, Moises A. Huaman, James Karrer, Karthik Kondapally, Sarah Mitchell, Jonathan Wortham, Sietske de Fijter
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

MDR TB is a form of tuberculosis caused by M. tuberculosis resistant to isoniazid and rifampin, two cornerstone drugs used in the first-line TB treatment regimen.
Poster Session 2: Hepatitis C: Approved Therapeutic Agents
Journal: Hepatology (2014)

Objectives: Sofosbuvir (SOF) is the first nucleotide polymerase inhibitor with pan-genotypic activity and a high barrier to resistance.Efficacy and safety have been demonstrated in five phase III clinical trials of SOF administered with either ribavirin (R) or a combination of pegylated interferon alfa and ribavirin (PR).SOF is also the first all-oral 24-week option available for patients unsuitable for interferon (UI).This analysis evaluated the cost-effectiveness of SOF in treatment-naïve (TN) genotype (GT) 1/4/5/6 and GT 2 and 3 patients who are TN, treatment-experienced (TE), interferon eligible (IE) and UI, in the UK.Methods: A Markov model followed a cohort of 10,000 patients over lifetime, with approximately 20% initiating treatment at the compensated cirrhotic stage.SOF/PR for 12 weeks was compared to telaprevir, boceprevir, PR and no treatment (NT); SOF/PR achieved 90% cure rates with only 12 weeks of treatment with no adverse drug reactions above those for PR.For patients UI SOF/RBV for either 12 or 24 weeks was compared to NT.The analysis took the perspective of the National Health Service.Results: SOF, including interferon-free regimens, was shown to be cost-effective across all genotypes (£17,981/ QALY).This is particularly the case for GT1 (£18,533/QALY) and GT3 (£18,450/QALY) which account for almost 90% of the patients infected with HCV in the UK.The 12-week interferon-free regimen is also highly cost-effective for GT2 with a combined ICER of £12,180/QALY.For the low-prevalent GT 4/5/6 SOF/PR is cost-effective at a £30,000/QALY threshold.These cost-effective combined ICERs remain valid in sensitivity analysis.Conclusions: SOF-based regimens are a cost-effective alternative to the current standard of care for HCV.SOF represents a major breakthrough in the treatment of HCV, making successful HCV cure a realistic possibility with the potential to reduce the long-term disease and economic burden of HCV to the public health system.
Genomic Predictors of Progression-Free Survival Among Patients with Relapsed or Refractory Multiple Myeloma Treated with Carfilzomib and Dexamethasone or Bortezomib and Dexamethasone in the Phase 3 Endeavor Trial
Authors: Robert J Pelham, Xuguang Hu, Philippe Moreau, Albert Oriol, Hang Quach, Tibor Kovacsovics, Jonathan J Keats, Shibao Feng, Amy S. Kimball, Meletios A. Dimopoulos
Journal: Blood (2017)
Effect of 6 Months of Flash Glucose Monitoring in Youth With Type 1 Diabetes and High-Risk Glycemic Control: A Randomized Controlled Trial
Authors: Sara E. Boucher, Andrew R. Gray, Esko J. Wiltshire, Martin I. de Bock, Barbara C. Galland, Paul A. Tomlinson, Jenny A. Rayns, Karen E. MacKenzie, Huan Chan, Shelley Rose, Benjamin J. Wheeler
Journal: Diabetes Care (2020)

OBJECTIVE To investigate whether intermittently scanned continuous glucose monitoring (isCGM) significantly improves glycemic control compared with capillary self-monitored blood glucose (SMBG) in youth with type 1 diabetes and high-risk glycemic control. RESEARCH DESIGN AND METHODS This multicenter 6-month randomized, controlled, parallel-arm trial included 64 participants aged 13–20 years with established type 1 diabetes and glycated hemoglobin (HbA1c) ≥9% (≥75 mmol/mol). Participants were allocated to 6-month intervention (isCGM; FreeStyle Libre; Abbott Diabetes Care, Witney, U.K.) (n = 33) or control (SMBG; n = 31) using minimization. The primary outcome was the difference in change in HbA1c from baseline to 6 months. RESULTS There was no evidence of a difference between groups for changes in HbA1c at 6 months (adjusted mean 0.2% greater improvement for isCGM [95% CI −0.9 to 0.5] [−2.1 mmol/mol (95% CI −9.6 to 5.4)]; P = 0.576). However, glucose-monitoring frequency was 2.83 (95% CI 1.72–4.65; P &amp;lt; 0.001) times higher in the isCGM group compared with that in the SMBG group at 6 months. The change in the Diabetes Treatment Satisfaction Questionnaire mean item score also favored isCGM at 6 months (P = 0.048), with no significant differences between groups for fear of hypoglycemia and quality of life (both general and diabetes specific) (all P &amp;gt; 0.1). CONCLUSIONS For youth with high-risk glycemic control, isCGM led to improvements in glucose testing frequency and diabetes treatment satisfaction. However, these did not translate to greater improvement in glycemic control over usual care with SMBG at 6 months.
Targeting transforming growth factor-β receptors in pulmonary hypertension
Authors: Christophe Guignabert, Marc Humbert
Journal: European Respiratory Journal (2020)

The transforming growth factor-β (TGF-β) superfamily includes several groups of multifunctional proteins that form two major branches, namely the TGF-β–activin–nodal branch and the bone morphogenetic protein (BMP)–growth differentiation factor (GDF) branch. The response to the activation of these two branches, acting through canonical (small mothers against decapentaplegic (Smad) 2/3 and Smad 1/5/8, respectively) and noncanonical signalling pathways, are diverse and vary for different environmental conditions and cell types. An extensive body of data gathered in recent years has demonstrated a central role for the cross-talk between these two branches in a number of cellular processes, which include the regulation of cell proliferation and differentiation, as well as the transduction of signalling cascades for the development and maintenance of different tissues and organs. Importantly, alterations in these pathways, which include heterozygous germline mutations and/or alterations in the expression of several constitutive members, have been identified in patients with familial/heritable pulmonary arterial hypertension (PAH) or idiopathic PAH (IPAH). Consequently, loss or dysfunction in the delicate, finely-tuned balance between the TGF-β–activin–nodal branch and the BMP–GDF branch are currently viewed as the major molecular defect playing a critical role in PAH predisposition and disease progression. Here we review the role of the TGF-β–activin–nodal branch in PAH and illustrate how this knowledge has not only provided insight into understanding its pathogenesis, but has also paved the way for possible novel therapeutic approaches.
In Familial ALS, Antisense Agent Reduces Disease-Related Proteins
Authors: Jennifer Abbasi
Journal: JAMA (2020)

An investigational antisense oligonucleotide drug improved cerebrospinal fluid (CSF) levels of the protein responsible for up to a fifth of familial amyotrophic lateral sclerosis (ALS) cases among people of European origin, researchers reported in the New England Journal of Medicine.