tbuckley/cabot-search huggingface dataset:
Fabrication and characterization of biodegradable Mg-Zn-Y-Nd-Ag alloy: Microstructure, mechanical properties, corrosion behavior and antibacterial activities
Authors: Yashan Feng, Shijie Zhu, Liguo Wang, Lei Chang, Yachen Hou, Shaokang Guan
Journal: Bioactive Materials (2018)

Magnesium (Mg), a potential biodegradable material, has drawn wide attention in the bone reconstruction field. However, Mg alloys, served as the bone graft substitution, remain a clinical challenge, the antibacterial activity of which is required to be enhanced. Here, we prepared biodegradable magnesium Mg-Zn-Y-Nd-Ag and then had it been further densified by extruding. The microstructure evolution of the as-cast and as-extruded Mg- Zn-Y-Nd-Ag was characterized using optical microscope and X-ray diffraction analyses (XRD). The results showed that the microstructure of the as-cast alloys was mainly dendrites, between which, the second phase was mainly distributed; with the increase of Ag additions, grain structure was further refined as well as the increase of amount of the second phase. After the extrusion, the grains were further refined. Microhardness tests indicated that both of the increase of Ag content and the extrusion process improved the microhardness of the alloys, specially the later. A systematic investigation of the in vivo antibacterial capability of Staphylococcus aurous and Escherichia coli was performed, and the results of which indicated that all Mg-Zn-Y-N-xAg (x = 0.2, 0.4, 0.6, 0.8) alloys exhibited certain antibacterial property, which would increased with the increase of Ag content. Taken all together, the antimicrobial property of the as-extruded alloy containing 0.4 wt% Ag exhibited the relatively better antimicrobial properties and mechanical property with the relatively small loss in corrosion resistance, which suggested the potential utility of as-extruded Mg-Zn-Y-N-0.4Ag in treating orthopedic infections.
Changes in liver function following real-world transarterial chemoembolization (TACE) in US patients (pts) with hepatocellular carcinoma (HCC): The LiverT study.
Authors: Rebecca A. Miksad, Sadahisa Ogasawara, Fang Xia, Marc Mardoche Fellous, Fabio Piscaglia
Journal: Journal of Clinical Oncology (2018)

441 Background: Acute elevations of serum transaminases and bilirubin after TACE are commonly observed in pts with HCC. However, real-world incidence of chronic liver damage after TACE is unclear. LiverT is a retrospective, observational study to assess potential chronic deterioration of liver function of HCC pts after a single TACE in US real-world practice. Methods: Eligible HCC pts underwent index TACE between Jan 1, 2010 and Mar 31, 2016 and did not undergo repeat/additional HCC treatment in the subsequent 90 days. Pts were identified from Optum’s integrated database using standard codes. At least one laboratory value was required within 30 days prior to index TACE (baseline = latest value within period) and 30–90 days after TACE (chronic period = latest value within period). Due to lack of universally accepted liver function deterioration criteria, clinically meaningful changes in laboratory parameters were predefined by experts (Table). Subgroup analyses explored the impact of HCC etiology, diabetes status, anticoagulation use, and presence of portal vein thrombosis. Results: Of 5142 Optum TACE pts, 572 (11%) were eligible; exclusions were primarily due to lack of HCC diagnostic code and laboratory availability; 411 (72%) were male and median age was 62 yrs. Although lower than acute liver deterioration (0–29 days post-TACE), 30–90 day chronic liver deterioration varied by parameter and ranged from 15% to 31% (Table). Overall, sub-groups showed similar patterns. Conclusions: We report real-world chronic deterioration of liver function 30–90 days after a single TACE in a cohort of HCC pts. Limitations include missing data, small sample size, and difficulty establishing causation. Subsequent HCC treatments may be limited by liver function; therefore, further characterization of post-TACE chronic deterioration of liver function for HCC is important. [Table: see text]
The participatory dimension of individual responsibility
Authors: Sofia Bonicalzi, Mattia Gallotti
Journal: Behavioral and Brain Sciences (2018)

Abstract Collaborativism is the view that moral reasoning is better when it is socially embedded. We propose that, when people take part in dialogic exchanges, they align in ways that open up novel avenues for sharing values and rationality criteria and, therefore, for exercising responsible agency. The hypothesis that collaborative interactions unfold through the alignment of minds and bodies helps articulate Doris's participatory approach to morality.
Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non–Small Cell Lung Cancer
Authors: Lorena Ostios-Garcia, Jennifer Faig, Giulia C. Leonardi, Anika E. Adeni, Safiya J. Subegdjo, Christine A. Lydon, Deepa Rangachari, Mark S. Huberman, Kartik Sehgal, Meghan Shea, Paul A. VanderLaan, Matthew P. Cheng, Francisco M. Marty, Sarah P. Hammond, Daniel B. Costa, Mark M. Awad
Journal: Journal of Thoracic Oncology (2018)
Abstract 17922: Scleroderma Associated Pulmonary Arterial Hypertension is Associated With a High Prevalence of Aortic Stenosis
Authors: Vikram Gurtu, Adam Kinnaird, Linda Webster, Evangelos Michelakis
Journal: Circulation (2016)

Introduction:  Traditional risk factors for aortic stenosis (AS) include age, male sex, hypertension, smoking, and dyslipidemia, while inflammation and increased bone morphogenetic protein (BMP) signaling have been implicated in disease progression. BMP signaling is suppressed in pulmonary arterial hypertension (PAH), and these patients are usually younger at the time of diagnosis, mostly female, and typically do not have traditional AS risk factors. On the other hand, PAH, and particularly scleroderma associated PAH (Scl-PAH) patients, have a high burden of systemic inflammation.   Hypothesis:  Following serial clinical observations, we hypothesized that the prevalence of AS would be higher in patients with Scl-PAH or idiopathic PAH (iPAH) compared to the normal population, where it is observed in 1% of women and 1.5% of men 65-75yo and in even less (0.6%) of patients 55-65yo.   Methods:  We reviewed ECHO and clinical data from a prospective database in our pulmonary hypertension clinic since 2002. This included Scl-PAH (n=116), iPAH (n=99), and chronic thromboembolic pulmonary hypertension (CTEPH, as a control group, n=98). The presence of AS, grade of disease, aortic valve area, peak aortic jet velocity and maximum aortic pressure gradient were analyzed.   Results:  In Scl-PAH vs iPAH vs CTEPH groups, the mean age was 55.8±1.3 vs 54.8±1.7 vs 59.9±1.7 years; the %females was, 87.1% vs 68.7% vs 61%; the mean PA pressure by catheterization was 34.8±2.4 vs 49.3±1.6 vs 43.1±1.2 mmHg, respectively. AS was present in 13.8% of Scl-PAH vs 6.1% of iPAH and 4.1% of CTEPH patients. The rate of progression of AS in Scl-PAH was 0.42m/s/year, a rate that in the general population is associated with worse outcomes.   Conclusions:  Patients with Scl-PAH may be a previously unidentified high-risk group for AS development, with high prevalence and fast progression rates. The AS risk is particularly high in these younger and mostly female patients considering the typical absence of known AS risk factors in Scl-PAH. If our data are confirmed in larger and multicenter cohorts, they would suggest a need for increased awareness for AS in Scl-PAH patients, whose serious co-morbidities and PAH-therapies (vasodilators, transplantation) can significantly complicate the management of AS.
BEACON CRC study safety lead-in (SLI) in patients with <i>BRAF</i><sup>V600E</sup> metastatic colorectal cancer (mCRC): Efficacy and tumor markers.
Authors: Eric Van Cutsem, Pieter-Jan Cuyle, Sanne Huijberts, Rona Yaeger, Jan H. M. Schellens, Elena Elez, Josep Tabernero, Marwan Fakih, Clara Montagut, Marc Peeters, Jayesh Desai, Takayuki Yoshino, Fortunato Ciardiello, Harpreet Singh Wasan, Scott Kopetz, Kati Maharry, Janna Christy-Bittel, Ashwin Gollerkeri, Axel Grothey
Journal: Journal of Clinical Oncology (2018)

627 Background: The SLI of the BEACON CRC phase 3 study assessed the safety and efficacy of the combination of the BRAF inhibitor encorafenib (ENCO) + MEK inhibitor binimetinib (BINI) + anti-EGFR antibody cetuximab (CETUX) in pts with BRAF V600E -mutant mCRC after 1 or 2 prior regimens. CEA and CA19-9 are tumor markers that are widely used to monitor the effectiveness of systemic therapies for mCRC; here we report on the association of CEA and CA19-9 changes while on treatment with clinical outcomes in pts from the SLI. Methods: Pts in the SLI received the triplet of ENCO 300 mg QD + BINI 45 mg BID + CETUX 400 mg/m 2 (initial dose) then 250 mg/m 2 QW in 28-day cycles. Pts were evaluated for safety, radiographic response, and change in tumor markers CEA and CA19-9. Results: 30 pts were treated. The triplet was generally well tolerated, and adverse events were consistent with known BRAF, MEK, and EGFR inhibitor toxicities. The rate of severe skin toxicities (grade 3/4) was lower than generally observed for CETUX in mCRC. Of the 29 pts with a BRAF V600E mutation, the median time on study treatment was 5.6 mo (range, 1.0–9.3 mo), and 22 (76%) remained on study treatment at the time of data cutoff. The confirmed overall response rate (ORR) was 41%, with 1 complete and 11 partial responses. In addition, 9 pts had prolonged stable disease (SD) up to 9.3 mo.CEA and CA19-9 were analyzed in 28 pts. CEA and CA19-9 decreased in 96% and 82% of these pts, respectively. Among 15 pts with treatment duration ≥5.6 mo, median/mean % decreases were 97%/79% for CEA and 92%/82% for CA19-9 in confirmed responders (n=6). Respective decreases in pts with prolonged SD (n=9) were similar: 84%/68% for CEA and 89%/68% for CA19-9. Updated safety, efficacy, and tumor marker results will be provided. Conclusions: ENCO + BINI + CETUX is generally well tolerated and has encouraging clinical activity in BRAF V 600E mCRC, with a confirmed ORR of 41%. In pts with study treatment duration ≥5.6 mo, the tumor markers CEA and CA19-9 decreased markedly and to the same degree in responders vs pts with prolonged SD, providing additional evidence of the meaningful clinical activity of this regimen. Clinical trial information: NCT02928224.
Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension
Authors: Yuichi Tamura, Carole Phan, Ly Tu, Morane Le Hiress, Raphaël Thuillet, Etienne-Marie Jutant, Elie Fadel, Laurent Savale, Alice Huertas, Marc Humbert, Christophe Guignabert
Journal: Journal of Clinical Investigation (2018)

Pulmonary arterial hypertension (PAH) is characterized by a progressive accumulation of pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterioles leading to the narrowing of the lumen, right heart failure, and death. Although most studies have supported the notion of a role for IL-6/glycoprotein 130 (gp130) signaling in PAH, it remains unclear how this signaling pathway determines the progression of the disease. Here, we identify ectopic upregulation of membrane-bound IL-6 receptor (IL6R) on PA-SMCs in PAH patients and in rodent models of pulmonary hypertension (PH) and demonstrate its key role for PA-SMC accumulation in vitro and in vivo. Using Sm22a-Cre Il6rfl/fl, which lack Il6r in SM22A-expressing cells, we found that these animals are protected against chronic hypoxia-induced PH with reduced PA-SMC accumulation, revealing the potent pro-survival potential of membrane-bound IL6R. Moreover, we determine that treatment with IL6R-specific antagonist reverses experimental PH in two rat models. This therapeutic strategy holds promise for future clinical studies in PAH.
Thomas Martin Richards
Authors: Keith Richards, Sara Richards
Journal: BMJ (2018)

Thomas Martin Richards (“Tom”) was born near Vienna, one of two boys. He was very much a self made man, being sent to school in England at a young age without parents in the country. He learnt the language and developed the desire to help others from an early age. He was intelligent, hardworking, good at sport, and a private individual with a mischievous sense of humour. He studied medicine at St Thomas’ Hospital, London, where he graduated in 1954, gaining the special surgery prize (obstetrics) in his final year. He also regularly played hockey, tennis, and squash for the hospital, which stood him in good stead when looking for a place to settle and become a town GP. He had also been in the army and a ship’s surgeon for a while and settled in England, …
Mitochondria Bound to Lipid Droplets Have Unique Bioenergetics, Composition, and Dynamics that Support Lipid Droplet Expansion
Authors: Ilan Y. Benador, Michaela Veliova, Kiana Mahdaviani, Anton Petcherski, Jakob D. Wikstrom, Essam A. Assali, Rebeca Acín-Pérez, Michaël Shum, Marcus F. Oliveira, Saverio Cinti, Carole Sztalryd, William D. Barshop, James A. Wohlschlegel, Barbara E. Corkey, Marc Liesa, Orian S. Shirihai
Journal: Cell Metabolism (2018)
Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition
Authors: Ramesh P Arasaradnam, Steven Brown, Alastair Forbes, Mark R Fox, Pali Hungin, Lawrence Kelman, Giles Major, Michelle O’Connor, Dave S Sanders, Rakesh Sinha, Stephen Charles Smith, Paul Thomas, Julian R F Walters
Journal: Gut (2018)

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.
The application of CAR-T cell therapy in hematological malignancies: advantages and challenges
Authors: Zijun Zhao, Yu Chen, Ngiambudulu M. Francisco, Yuanqing Zhang, Minhao Wu
Journal: Acta Pharmaceutica Sinica B (2018)

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.
Innate valuation, existential framing, and one head for multiple moral hats
Authors: Bree Beal, Philippe Rochat
Journal: Behavioral and Brain Sciences (2018)

Abstract We support John Doris's criticism of “reflectivism” but identify three shortcomings: (1) his neglect of humans' evolved predispositions and tendencies, (2) his failure to appreciate that identity and responsibility arise first from parsing our world ontologically, in a process we call “existential framing,” and (3) a potentially alarming implication of his “dialogic” model of identity formation: if identity is negotiated across diverse social situations, why isn't dissociative identity disorder more common?
Recurrent rate of high-risk adenoma after screening colonoscopy.
Authors: Bunchorn Siripongpreeda, Pornpeera Jitpratoom, Watanya Chaiwong, Wipra Worasawate, Kanlayarat Leesuksawat, Kulwadee Suthivaiyakit, Thaniya Sricharunrat, Narongchai Teerayathanakul, Prassanee Sattarungsee, Jirapa Prarom, Pinitporn Khanpaeng, Gaidganok Sornsamdang, Kasiruck Wittayasak, Kamonwan Soonklang
Journal: Journal of Clinical Oncology (2014)

e14617 Background: Screening colonoscopy has not been routinely offered in Thailand despite the increasing occurrence of colorectal cancer (CRC) in the country. We previously reported the results of 1,404 colonoscopic screening of Thai individuals aged 50-65 years, revealing the prevalence of CRC and high-risk adenoma of 1.28% and 7%, respectively. This study aimed to evaluate the 3-year surveillance results of high-risk adenoma cases diagnosed at baseline. Methods: After screening colonoscopy and intervention at baseline, the cases with a history of high-risk (>1 cm, high-grade dysplasia, villous adenoma, or tubulovillous adenoma) or multiple adenoma (≥ 3 polyps) were identified. All cases received a second colonoscopy 3 years apart. Fecal immunochemical test (FIT) was also performed before each colonoscopy. Results: Of 98 cases with high-risk or multiple adenoma at baseline, eighty-four cases underwent second colonoscopy, whereas 14 cases did not. Of those 84 cases, one patient (1.19%) was found to have intramucosal adenocarcinoma and 40 cases (47.62%) had recurrent adenomatous polyp(s). Fourteen of the primary high-risk group continued to have a high-risk or multiple adenoma. FIT was positive in 3 of the recurrent high-risk cases and also positive in the carcinoma case. FIT was negative in 68 out of the 84 cases. The sensitivity and specificity of FIT in predicting any adenomatous lesions or cancer were 21.95% and 83.72%, respectively. Conclusions: The rate of recurrent adenomatous polyps or new malignant lesion development in 3 years after having a high-risk or multiple adenoma at baseline screening colonoscopy is very high. Short term follow-up with second colonoscopy in such cases is strongly recommended. Although FIT could identify the new CRC case in this study, its ability to detect any recurrent polyps is low.
An Evaluation of Function of Multicopy Noncoding RNAs in Mammals Using ENCODE/FANTOM Data and Comparative Genomics
Authors: Marc P Hoeppner, Elena Denisenko, Paul P Gardner, Sebastian Schmeier, Anthony M Poole
Journal: Molecular Biology and Evolution (2018)

Mammalian diversification has coincided with a rapid proliferation of various types of noncoding RNAs, including members of both snRNAs and snoRNAs. The significance of this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as a result of random retrotransposition. Hindering progress in our understanding of such observations is the difficulty in establishing function for the diverse features that have been identified in our own genome. Projects such as ENCODE and FANTOM have revealed a hidden world of genomic expression patterns, as well as a host of other potential indicators of biological function. However, such projects have been criticized, particularly from practitioners in the field of molecular evolution, where many suspect these data provide limited insight into biological function. The molecular evolution community has largely taken a skeptical view, thus it is important to establish tests of function. We use a range of data, including data drawn from ENCODE and FANTOM, to examine the case for function for the recent copy number expansion in mammals of six evolutionarily ancient RNA families involved in splicing and rRNA maturation. We use several criteria to assess evidence for function: conservation of sequence and structure, genomic synteny, evidence for transposition, and evidence for species-specific expression. Applying these criteria, we find that only a minority of loci show strong evidence for function and that, for the majority, we cannot reject the null hypothesis of no function.
Impact of intravascular thrombosis on failure of radial arterial catheters in critically ill patients: a nested case-control study
Authors: Yvan Fleury, Diego Arroyo, Caroline Couchepin, Helia Robert-Ebadi, Marc Righini, Johannes A. Lobrinus, Bara Ricou, Nathalie Delieuvin Schmitt, Angèle Gayet-Ageron
Journal: Intensive Care Medicine (2018)
Tackling socioeconomic inequalities and non-communicable diseases in low-income and middle-income countries under the Sustainable Development agenda
Authors: Louis W Niessen, Diwakar Mohan, Jonathan K Akuoku, Andrew J Mirelman, Sayem Ahmed, Tracey P Koehlmoos, Antonio Trujillo, Jahangir Khan, David H Peters
Journal: The Lancet (2018)
The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia
Authors: Jingwei Sim, Andrew S. Cowburn, Asis Palazon, Basetti Madhu, Petros A. Tyrakis, David Macías, David M. Bargiela, Sandra Pietsch, Michael Gralla, Colin E. Evans, Thaksaon Kittipassorn, Yu C.J. Chey, Cristina M. Branco, Helene Rundqvist, Daniel J. Peet, Randall S. Johnson
Journal: Cell Metabolism (2018)

Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia.
Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial
Authors: Masatoshi Kudo, Kazuomi Ueshima, Osamu Yokosuka, Sadahisa Ogasawara, Shuntaro Obi, Namiki Izumi, Hiroshi Aikata, Hiroaki Nagano, Etsuro Hatano, Yutaka Sasaki, Keisuke Hino, Takashi Kumada, Kazuhide Yamamoto, Yasuharu Imai, Shouta Iwadou, Chikara Ogawa, Takuji Okusaka, Fumihiko Kanai, Kohei Akazawa, Ken-ichi Yoshimura, Philip Johnson, Yasuaki Arai, Masatoshi Kudo, Kazuomi Ueshima, Osamu Yokosuka, Sadahisa Ogasawara, Shuntaro Obi, Namiki Izumi, Hiroshi Aikata, Hiroaki Nagano, Etsuro Hatano, Yutaka Sasaki, Keisuke Hino, Takashi Kumada, Kazuhide Yamamoto, Yasuharu Imai, Shouta Iwadou, Chikara Ogawa, Takuji Okusaka, Fumihiko Kanai, Kohei Akazawa, Ken-ichi Yoshimura, Philip Johnson, Yasuaki Arai
Journal: The Lancet. Gastroenterology & hepatology (2018)