tbuckley/cabot-search huggingface dataset:
Plasma Biomarkers of Inflammation and Angiogenesis Predict Cerebral Cavernous Malformation Symptomatic Hemorrhage or Lesional Growth
Authors: Romuald Girard, Hussein A. Zeineddine, Janne Koskimäki, Maged D. Fam, Ying Cao, Changbin Shi, Thomas Moore, Rhonda Lightle, Agnieszka Stadnik, Kiranj Chaudagar, Sean Polster, Robert Shenkar, Ryan Duggan, David Leclerc, Kevin J. Whitehead, Dean Y. Li, Issam A. Awad
Journal: Circulation Research (2018)

The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers with prior disease severity.We hypothesize that a panel of 24 candidate plasma biomarkers, with a reported role in the physiopathology of cerebral cavernous malformations, may predict subsequent clinically relevant disease activity.Plasma biomarkers were assessed in nonfasting peripheral venous blood collected from consecutive cerebral cavernous malformation subjects followed for 1 year after initial sample collection. A first cohort (N=49) was used to define the best model of biomarker level combinations to predict a subsequent symptomatic lesional hemorrhagic expansion within a year after the blood sample. We generated the receiver operating characteristic curves and area under the curve for each biomarker individually and each weighted linear combination of relevant biomarkers. The best model to predict lesional activity was selected as that minimizing the Akaike information criterion. In this cohort, 11 subjects experienced symptomatic lesional hemorrhagic expansion (5 bleeds and 10 lesional growths) within a year after the blood draw. Subjects had lower soluble CD14 (cluster of differentiation 14; P=0.05), IL (interleukin)-6 (P=0.04), and VEGF (vascular endothelial growth factor; P=0.0003) levels along with higher plasma levels of IL-1β (P=0.008) and soluble ROBO4 (roundabout guidance receptor 4; P=0.03). Among the 31 weighted linear combinations of these 5 biomarkers, the best model (with the lowest Akaike information criterion value, 25.3) was the weighted linear combination including soluble CD14, IL-1β, VEGF, and soluble ROBO4, predicting a symptomatic hemorrhagic expansion with a sensitivity of 86% and specificity of 88% (area under the curve, 0.90; P<0.0001). We then validated our best model in the second sequential independent cohort (N=28).This is the first study reporting a predictive association between plasma biomarkers and subsequent cerebral cavernous malformation disease clinical activity. This may be applied in clinical prognostication and stratification of cases in clinical trials.
Kidney-targeted inhibition of protein kinase C-α ameliorates nephrotoxic nephritis with restoration of mitochondrial dysfunction
Authors: Nino Kvirkvelia, Malgorzata McMenamin, Marie Warren, Ravirajsinh N. Jadeja, Sai Karthik Kodeboyina, Ashok Sharma, Wenbo Zhi, Paul M. O’Connor, Raghavan Raju, Rudolf Lucas, Michael P. Madaio
Journal: Kidney International (2018)
Indian paediatrician arrested over deaths of dozens of children gets bail after campaign to free him
Authors: Dinsa Sachan
Journal: BMJ (2018)

A doctor whose arrest in connection with the deaths of more than 70 children at a hospital in India and that led to a public campaign to free him has been granted bail.

Kafeel Khan, a paediatrician at a hospital in Gorakhpur, Uttar Pradesh, was arrested in September last year after more than 70 children died in Gorakhpur’s Baba Raghav Das Medical College Hospital within a week last August.1

A government probe found that the hospital had run out of oxygen cylinders and that this had led to the deaths, mostly in the hospital’s neonatal and encephalitis wards.2 Delivery of oxygen cylinders had been disrupted because suppliers hadn’t …
P460The new approach for nanoparticles detection using flow cytometry
Authors: A Golovkin, K Kondratov, V Kishenko, A Fedorov, I Kudryavtsev, M Belyakova, T Vavilova, O Sirotkina
Journal: Cardiovascular Research (2018)

HfcMSC were seeded on NT2repCT 3D scaffolds at the bottom of 50 ml test tubes.After 2-8 weeks the scaffolds were frozen and sectioned.Immunohistochemistry was used to assess expression of cell markers and formation of extracellular matrix.Results: HfcMSC attach to NT2repCT through focal adhesions, form networks, survive and proliferate for at least 8 weeks.The cells grow in vessel-like structures expressing alpha smooth muscle actin, CD31 and Laminin alpha 4 and 5. Laminin expression co-localized with dense staining of heparan sulfate, indicating formation of basal membranes. Conclusion:We have shown that hfcMSC can be cultured on artificial spider silk and are capable of producing specific laminins important in healing and angiogenesis.To enhance cardiac tissue recovery after a myocardial infarction supportive tissue and angiogenesis are very important.The study of supportive cells in a relevant in vitro model can both enhance our basic knowledge and provide better ways for in vitro assessment of drug effects and toxicity.
Collagen proportionate área is an independent predictor of long term outcome in patients with alcoholic liver disease
Authors: M.G. Misas, A. Koutsoumarakis, Y. Huang, M. Thiele, A. Hall, C. Covelli, E. Buzzetti, L.I. Prat, D. Roccarina, S. Detlefsen, T.V. Luong, G. Jeffrey, M. Pinzani, E. Tsochatzis
Journal: Journal of Hepatology (2018)
Scintigraphic and Sonographic Findings of Subcapsular Cortical Necrosis in a Transplanted Kidney
Authors: Bulent Yazici, Emrah Gunay, Aysegül Akgün, Sait Sen, Suha Sureyya Ozbek
Journal: Clinical Nuclear Medicine (2018)

Renal transplant scintigraphy, performed in a 23-year-old man who had renal graft from a living donor, showed nearly normal perfusion and moderately low function of the graft. But the margins of the graft were blurred, and it was interestingly appearing enlarged late in the study. Ultrasound demonstrated a hypoechoic rim surrounding the whole kidney. Biopsy revealed necrosis besides normal cortical tissue. Necrosis was thought to be limited to the subcapsular cortical area. It should be considered that these scintigraphic findings could be due to greatly reduced and delayed perfusion of edematous subcapsular necrotic area of the graft even in normal perfusion images.
Impact of molecular tumor board on late-stage gastrointestinal malignancies at a tertiary center.
Authors: Timothy Lewis Cannon, Jo-Ellen Murphy, Jennifer Carter, Donald L. Trump, Sheryl Krevsky Elkin, Anam Asif, Laura Knopp, John Milburn Jessup
Journal: Journal of Clinical Oncology (2018)

483 Background: Inova Schar Cancer Institute formed a molecular tumor board in early 2016 to identify treatment options for patients with gastrointestinal malignances based on molecular testing and to track outcomes. Methods: From March 2016 to June 2017, 78 patients with advanced gastrointestinal malignancies were presented at our molecular tumor board. The most common mutations, the percentage of patients who received targeted therapies, responded to targeted therapies, died or went on hospice prior to receiving a recommended therapy, and had an available Association of Molecular Pathology Tier 1 or Tier 2 recommendation available were reviewed retrospectively. We also compared the overall survival of patients who received a new treatment after MTB compared to those who did not. N-of-One, Inc. provided curation of molecular testing and participated in the MTB. Results: 78 patients with gastrointestinal cancers were presented between March 2016 and June 2017. Thirteen (19%) patients received targeted therapy and 31% had partial response, 15% had Stable Disease, and 54% had progression of disease. 12 patients (15%) died or went on hospice before recommendations could start and 11 patients (14%) are waiting to start recommended therapy. 38 (49%) patients did not have a mutation that prompted a MTB recommendation. Median OS of the 33 patients who started a new therapy (including chemotherapy or unrelated clinical trials) after MTB was 15.3 months vs. 11.5 months in 40 patients who continued current therapy (P = 0.016 Wilcoxon). The three most common mutations detected were TP53, KRAS, and APC. The majority of cases had more than one variant. 18% of cases had a variant classified as Tier 1; 74% of cases had a variant with the highest AMP classification of Tier 2. Conclusions: The majority of patients with Gastrointestinal malignancies presented to the Inova MTB had a finding that supported a molecularly-guided therapy, with a small but meaningful number of partial responses. Barriers to the use of molecular guided therapy included molecular testing and presentation at a late disease stage, and alternative chemotherapeutic options.
Risk and outcome of hepatitis B virus reactivation during chronic hepatitis C treatment with direct-acting antivirals in patients with HCV-related advanced fibrosis: a single-center experience
Authors: R. D’ambrosio, E. Degasperi, A. Aghemo, M. Borghi, R. Perbellini, S.D. Nicola, G. Lunghi, P. Lampertico
Journal: Journal of Hepatology (2018)
Association Between Early Postoperative Acetaminophen Exposure and Acute Kidney Injury in Pediatric Patients Undergoing Cardiac Surgery
Authors: Sara L. Van Driest, Edmund H. Jooste, Yaping Shi, Leena Choi, Leon Darghosian, Kevin D. Hill, Andrew H. Smith, Prince J. Kannankeril, Dan M. Roden, Lorraine B. Ware
Journal: JAMA Pediatrics (2018)

Acute kidney injury (AKI) is a common and serious complication for pediatric cardiac surgery patients associated with increased morbidity, mortality, and length of stay. Current strategies focus on risk reduction and early identification because there are no known preventive or therapeutic agents. Cardiac surgery and cardiopulmonary bypass lyse erythrocytes, releasing free hemoglobin and contributing to oxidative injury. Acetaminophen may prevent AKI by reducing the oxidation state of free hemoglobin.To test the hypothesis that early postoperative acetaminophen exposure is associated with reduced risk of AKI in pediatric patients undergoing cardiac surgery.In this retrospective cohort study, the setting was 2 tertiary referral children's hospitals. The primary and validation cohorts included children older than 28 days admitted for cardiac surgery between July 1, 2008, and June 1, 2016. Exclusion criteria were postoperative extracorporeal membrane oxygenation and inadequate serum creatinine measurements to determine AKI status.Acetaminophen exposure in the first 48 postoperative hours.Acute kidney injury based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (increase by ≥0.3 mg/dL from baseline or at least 1.5-fold more than the baseline [to convert to micromoles per liter, multiply by 88.4]) in the first postoperative week.The primary cohort (n = 666) had a median age of 6.5 (interquartile range [IQR], 3.9-44.7) months, and 341 (51.2%) had AKI. In unadjusted analyses, those with AKI had lower median acetaminophen doses than those without AKI (47 [IQR, 16-88] vs 78 [IQR, 43-104] mg/kg, P < .001). In logistic regression analysis adjusting for age, cardiopulmonary bypass time, red blood cell distribution width, postoperative hypotension, nephrotoxin exposure, and Risk Adjustment for Congenital Heart Surgery score, acetaminophen exposure was protective against postoperative AKI (odds ratio, 0.86 [95% CI, 0.82-0.90] per each additional 10 mg/kg). Findings were replicated in the validation cohort (n = 333), who had a median age of 14.1 (IQR, 3.9-158.2) months, and 162 (48.6%) had AKI. Acetaminophen doses were 60 (95% CI, 40-87) mg/kg in those with AKI vs 70 (95% CI, 45-94) mg/kg in those without AKI (P = .03), with an adjusted odds ratio of 0.91 (95% CI, 0.84-0.99) for each additional 10 mg/kg.These results indicate that early postoperative acetaminophen exposure may be associated with a lower rate of AKI in pediatric patients who undergo cardiac surgery. Further analysis to validate these findings, potentially through a prospective, randomized trial, may establish acetaminophen as a preventive agent for AKI.
Abstract 16087: A Propensity Matched Comparison of a Hybrid Approach of Percutaneous Coronary Intervention Followed by Minimally Invasive Valve Surgery versus Conventional Median Sternotomy Coronary Artery Bypass Graft Plus Valve Surgery
Authors: Andres M Pineda, Christos G Mihos, Solomon C Yang, Orlando Santana, Joseph Lamelas, Nirat Beohar
Journal: Circulation (2014)

Introduction: A hybrid approach of PCI followed by minimally invasive valve surgery (MIVS) has been recently introduced as an alternative for patients with concomitant coronary artery and valvular heart disease. Hypothesis: A hybrid approach might be better than the conventional median sternotomy CABG plus valve surgery for such patients. Methods: We retrospectively evaluated 525 consecutive patients with concomitant coronary artery and valvular heart disease who underwent surgical intervention at our institution between January 2009 and April 2014. A propensity score matching was performed to adjust for differences between the hybrid and the conventional groups. Results: A total of 63 patients who underwent a hybrid approach were propensity score-matched with a cohort of 63 conventional approach patients. There were no differences in the baseline characteristics (Table). Most patients in the hybrid group had drug-eluting stents (83%) placed for single (44.4%) or dual (50.8%) vessel disease, and within a median of 40 days, underwent single (87%) or double (13%) valve surgery. There was no difference in the type of valve surgery between the groups. Post-operatively, patients in the hybrid group had significantly shorter intensive care unit length of stay, fewer packed red blood cell units transfused, and a decreased incidence of re-intubation, prolonged ventilation, and acute kidney injury. There was no difference between the groups in other post-operative complications, including cerebrovascular accidents, re-operation for bleeding, atrial fibrillation, and 30-day mortality. At long-term follow-up (mean 29 months) the overall all-cause mortality was 9.5%, and the Kaplan-Meier estimated 5-year survival rates were similar (85 vs 90%, p =0.45). Conclusions: A hybrid approach of PCI followed by MIVS is associated with a decreased morbidity, and similar short and long-term survival when compared with conventional median sternotomy CABG plus valve surgery.
IFN-free DAA treatment of cirrhotic HCV patients with or without history of HCC: a multicenter prospective trial in Italy
Authors: A. Sangiovanni, E. Alimenti, M. Barone, L.S. Belli, E. Biganzoli, G. Borgia, M. Brunacci, M. Brunetto, R. D’ambrosio, S. Fargion, R. Filomia, M. Gambato, R. Gattai, E.G. Giannini, S. Maimone, L. Marzi, F. Oliveri, G. Pellegatta, G. Raimondo, M.G. Rumi, F.P. Russo, I. Serio, N. Terreni, L. Valenti, E. Villa, P. Lampertico
Journal: Journal of Hepatology (2018)
Estrogen receptors orchestrate cell growth and differentiation to facilitate liver regeneration
Authors: Ta-Lun Kao, Yu-Ping Kuan, Wei-Chung Cheng, Wei-Chun Chang, Long-Bin Jeng, Shuyuan Yeh, Wen-Lung Ma
Journal: Theranostics (2018)

Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships. Human hepatic progenitors (HepRG cells) and mouse Hepa1-6 hepatocytes were used to elucidate molecular interactions and functions. Results: This paper demonstrated that estrogen signals orchestrate hepatic repopulation and differentiation via distinct transcriptome patterns governed by ERα or ERβ. Cell repopulation pathway was associated with the ERα-transcriptome, but cell differentiation and metabolic function were associated with the ERβ transcriptome. Mechanistic studies linking ERs interactomes and transcriptomes discovered that ERα-Chd1 interaction promoted cell growth by upregulating Ssxb6, Crygc, and Cst1; and, ERβ-Ube3a interaction facilitated hepatic progenitor cell differentiation to hepatocytes and cholangiocytes, specifically by upregulating Ifna5. Conclusions: ERα and ERβ orchestrate liver cell proliferation and differentiation respectively, thereby promoting LR.
The development of the diabetes liver fibrosis score: A new prediction model to detect advanced fibrosis in diabetics with nonalcoholic fatty liver disease
Authors: A. Singh, R. Lopez, A. Vigni, E. Lawitz, F. Poordad, A. Scott, T. Okubote, M. Scott, M. Mansouri, N. Alkhouri
Journal: Journal of Hepatology (2018)
Two pathways, one patient; UK asthma guidelines
Authors: Stephen J Fowler, Paul M O’Byrne, Roland Buhl, Dominick Shaw
Journal: Thorax (2018)

The first widely disseminated ‘asthma guideline’ came out of Australia and New Zealand in 1989,1 followed shortly by the British Thoracic Society (BTS) in 1990,2 the United States National Heart, Lung, and Blood Institute Expert Panel Report in 19913 and the Global Initiative for Asthma (GINA) strategy document in 1995.4 All have benefited from regular updates, the BTS collaborating with the Scottish Intercollegiate Guideline Network (SIGN) since 2003, most recently in 2016.5 Each new iteration of the asthma guidelines was written by experts in the field and based on best available evidence. It is not known whether these guidelines (or any others) have improved the care of people with asthma; asthma prevalence has continued to rise (although it may now have plateaued), and deaths overall have not fallen, although this statistic is driven entirely by an ageing population, as deaths in England from asthma in the young have in fact dropped dramatically.6 It is likely, however, that guidelines have reduced variation in diagnosis and treatment of this complex disease.

In 2013, the National Institute for Health and Clinical Excellence (NICE) joined the guideline party, with a new approach that included consideration of health economics as well as clinical effectiveness. Their rationale included concerns that deaths were not falling, drug costs were rising and over-diagnosis and under-diagnosis still a significant issue. While the strength of evidence for each of these points varies (drug costs are rising across all areas of medicine, and over-diagnosis rates of 30% have been demonstrated repeatedly, even in recently diagnosed individuals7), all healthcare professionals involved in the care of people with asthma would recognise that each of these issues do need careful consideration. However, what had not been established was whether these failures were …
Black Phosphorus Hydrogels: Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy (Adv. Healthcare Mater. 7/2018)
Authors: Chenyang Xing, Shiyou Chen, Meng Qiu, Xin Liang, Quan Liu, Qingshuang Zou, Zhongjun Li, Zhongjian Xie, Dou Wang, Biqin Dong, Liping Liu, Dianyuan Fan, Han Zhang
Journal: Advanced Healthcare Materials (2018)

In article number 1701510, Liping Liu, Han Zhang, and co-workers demonstrate that green and injectable composite hydrogels based on cellulose and Black Phosphorus (BP) nanosheets (BPNSs) are of great efficiency for photothermal therapy (PTT) against cancer. The cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility.
MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1
Authors: Nina Schmolka, Pedro H. Papotto, Paula Vargas Romero, Tiago Amado, Francisco J. Enguita, Ana Amorim, Ana F. Rodrigues, Katrina E. Gordon, Ana S. Coroadinha, Mark Boldin, Karine Serre, Amy H. Buck, Anita Q. Gomes, Bruno Silva-Santos
Journal: Science Immunology (2018)

γδ T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27-) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- T cells in vitro and in vivo. On the basis of biochemical purification of Argonaute 2-bound miR-146a targets, we identified Nod1 to be a relevant mRNA target that regulates γδ T cell plasticity. In line with this, Nod1-deficient mice lacked multifunctional IL-17+ IFN-γ+ γδ27- cells and were more susceptible to Listeria monocytogenes infection. Our studies establish the miR-146a/NOD1 axis as a key determinant of γδ T cell effector functions and plasticity.
Effective multicomponent interventions in comparison to active control and no interventions on physical capacity, cognitive function and instrumental activities of daily living in elderly people with and without mild impaired cognition – A systematic review and network meta-analysis
Authors: Marina Bruderer-Hofstetter, Anne-Kathrin Rausch-Osthoff, André Meichtry, Thomas Münzer, Karin Niedermann
Journal: Ageing Research Reviews (2018)
Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope
Authors: Kannan Tharakaraman, Satoru Watanabe, Kuan Rong Chan, Jia Huan, Vidya Subramanian, Yok Hian Chionh, Aditya Raguram, Devin Quinlan, Megan McBee, Eugenia Z. Ong, Esther S. Gan, Hwee Cheng Tan, Anu Tyagi, Shashi Bhushan, Julien Lescar, Subhash G. Vasudevan, Eng Eong Ooi, Ram Sasisekharan
Journal: Cell Host & Microbe (2018)
Adiposity, body composition and ventricular–arterial stiffness in the elderly: the Atherosclerosis Risk in Communities Study
Authors: Miguel M. Fernandes‐Silva, Amil M. Shah, Brian Claggett, Susan Cheng, Hirofumi Tanaka, Odilson M. Silvestre, Wilson Nadruz, Barry A. Borlaug, Scott D. Solomon
Journal: European Journal of Heart Failure (2018)