tbuckley/cabot-search huggingface dataset:
Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation
Authors: Alexander S. Caldwell, Gavin T. Campbell, Kelly M. T. Shekiro, Kristi S. Anseth
Journal: Advanced Healthcare Materials (2017)

While microporous scaffolds are increasingly used for regenerative medicine and tissue repair applications, the most common techniques to fabricate these scaffolds use templating or top‐down fabrication approaches. Cytocompatible bottom‐up assembly methods afford the opportunity to assemble microporous systems in the presence of cells and create complex polymer‐cell composite systems in situ. Here, microgel building blocks with clickable surface groups are synthesized for the bottom‐up fabrication of porous cell‐laden scaffolds. The facile nature of assembly allows for human mesenchymal stem cells to be incorporated throughout the porous scaffold. Particles are designed with mean diameters of ≈10 and 100 µm, and assembled to create varied microenvironments. The resulting pore sizes and their distribution significantly alter cell morphology and cytoskeletal formation. This microgel‐based system provides numerous tunable properties that can be used to control multiple aspects of cellular growth and development, as well as providing the ability to recapitulate various biological interfaces.
EXPEDITION-I: efficacy and safety of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 infection and compensated cirrhosis
Authors: X. Forns, S. Lee, J. Valdes, S. Lens, R. Ghalib, H. Aguilar, F. Felizarta, T. Hassanein, H. Hinrichsen, D. Rincon, R. Morillas, S. Zeuzem, Y. Horsmans, D. Nelson, Y. Yu, T. Pilot-Matias, C.-W. Lin, F. Mensa
Journal: Journal of Hepatology (2017)
Drop-out rate due to HCC progression is not affected by HCV eradication with DAAs in patients awaiting liver transplantation
Authors: S. Shalaby, A. Zanetto, A. Vitale, A. Ferrarese, I. Bortoluzzi, M. Gambato, M. Senzolo, G. Germani, C. Mescoli, A. Romano, E. Gringeri, G. Zanus, P. Angeli, U. Cillo, P. Burra, F.P. Russo
Journal: Journal of Hepatology (2017)
Patients with severe mental illness have greatly increased cardiovascular risk, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Patients with severe mental illness, including schizophrenia, bipolar disorder, and major depressive disorder, have 53% higher odds of cardiovascular disease (CVD) than matched controls without these conditions, a large meta-analysis has found.1

Life expectancy in people with severe mental illness is shorter by 10.0-17.5 years than among the general population, and CVD is one of the major contributors to early deaths. Previous studies have shown increased risk of CVD in people with severe …
The effect of directly acting antivirals treatment on inflammatory status in HCV-infected patients, including those with recurrence of HCV-infection after liver transplantation: preliminary results of a prospective monocentric pilot study
Authors: B. Lattanzi, S. Baroncelli, L. Palmisano, C.M. Galluzzo, Z. Michelini, M. Lupo, A. De Santis, S.G. Corradini, G. Mennini, M. Rossi, M. Merli
Journal: Journal of Hepatology (2017)
Global Reprogramming of Host Kinase Signaling in Response to Fungal Infection
Authors: Aseem Pandey, Sheng Li Ding, Qing-Ming Qin, Rahul Gupta, Gabriel Gomez, Furong Lin, Xuehuan Feng, Luciana Fachini da Costa, Sankar P. Chaki, Madhu Katepalli, Elizabeth D. Case, Erin J. van Schaik, Tabasum Sidiq, Omar Khalaf, Angela Arenas, Koichi S. Kobayashi, James E. Samuel, Gonzalo M. Rivera, Robert C. Alaniz, Sing-Hoi Sze, Xiaoning Qian, William J. Brown, Allison Rice-Ficht, William K. Russell, Thomas A. Ficht, Paul de Figueiredo
Journal: Cell Host & Microbe (2017)

Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities. Deletion of Prkaa1, the gene encoding AMPKα1, in monocytes results in resistance to fungal colonization of mice. Finally, the recruitment of AIC components to nascent Cryptococcus-containing vacuoles (CnCVs) regulates the intracellular trafficking and replication of the pathogen. These findings demonstrate that host AIC regulatory networks confer susceptibility to infection and establish a proteomic resource for elucidating host mechanisms that regulate fungal intracellular parasitism.
Androgen signaling negatively controls group 2 innate lymphoid cells
Authors: Sophie Laffont, Eve Blanquart, Magali Savignac, Claire Cénac, Gilles Laverny, Daniel Metzger, Jean-Philippe Girard, Gabrielle T. Belz, Lucette Pelletier, Cyril Seillet, Jean-Charles Guéry
Journal: The Journal of Experimental Medicine (2017)

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33-driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33-mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33-driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.
Contempt, like any other social affect, can be an emotion as well as a sentiment
Authors: Roger Giner-Sorolla, Agneta H Fischer
Journal: Behavioral and Brain Sciences (2017)

Abstract Gervais &amp; Fessler assert that contempt is (a) not an emotion (or an attitude) but (b) a sentiment. Here, we challenge the validity and empirical basis of these two assertions, arguing that contempt, like many other emotions, can be both an emotion and a sentiment.
Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1–Positive Endometrial Cancer: Results From the KEYNOTE-028 Study
Authors: Patrick A. Ott, Yung-Jue Bang, Dominique Berton-Rigaud, Elena Elez, Michael J. Pishvaian, Hope S. Rugo, Igor Puzanov, Janice M. Mehnert, Kyaw L. Aung, Juanita Lopez, Marion Carrigan, Sanatan Saraf, Mei Chen, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2017)

Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti–programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) –positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1–positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016. Results Of 75 patients screened, 36 (48.0%) had PD-L1–positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in ≥ 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1–positive endometrial cancer.
Elevated levels of circulating osteopontin in patients with cholangiocarcinoma predict poor survival after tumor resection
Authors: S.H. Loosen, K.L. Kauertz, I. Pombeiro, F. Benz, F. Schüller, T. Longerich, C. Trautwein, U.P. Neumann, C. Roderburg, T. Luedde
Journal: Journal of Hepatology (2017)
Radiotherapy Rescue of a Nivolumab-Refractory Immune Response in a Patient with PD-L1–Negative Metastatic Squamous Cell Carcinoma of the Lung
Authors: Zhigang Yuan, Allison Fromm, Kamran A. Ahmed, George D. Grass, George Q. Yang, Daniel E. Oliver, Thomas J. Dilling, Scott J. Antonia, Bradford A. Perez
Journal: Journal of Thoracic Oncology (2017)
AML patients with <i>IDH1</i> or <i>IDH2</i> mutations treated with hypomethylating agents: A case series.
Authors: Christopher Brent Benton, Farhad Ravandi, Michael Andreeff, Hagop Kantarjian, Marina Konopleva
Journal: Journal of Clinical Oncology (2012)

6576 Background: Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations play a significant role in acute myeloid leukemia (AML), yet optimal treatment for AML patients with IDH mutations remains unclear. IDH mutations have been associated with a globally hypermethylated genomic state, as the result of increased levels of 2-HG, a regulator of histone methylation. We sought to retrospectively determine responses of patients with IDH-mutated AML to treatment with hypomethylating agents. Methods: We reviewed clinical data for AML patients treated at The University of Texas M. D. Anderson Cancer Center from June 2001 to December 2011 whose stored leukemia samples from bone marrow aspirateshad been tested retrospectively for IDH1 and IDH2 mutations. We searched three databases that contained records for 407 AML patients. We selected patients who had been treated with the hypomethylating agents 5-azacitidine or decitabine, alone or in conjunction with other therapeutics. We retrospectively reviewed the patients’ medical records to obtain demographic, laboratory, treatment, and clinical data. We evaluated response measured by remission status, reduction in bone marrow blasts and peripheral blood blasts, and time to relapse. Results: We identified 104 patients (25.6%) who had either an IDH1 or IDH2 mutation, and of these, 8 patients had also been treated with hypomethylating agents. A ninth AML patient, who is IDH2-mutant, is currently undergoing treatment with decitabine alone. Of these 9 patients, three had a durable complete remission without recovery of blood counts (CRp), three had a partial response (PR), with or without blood count recovery, and three had no response. All 9 patients did have an initial decrease in the percentage of bone marrow blasts, peripheral blood blasts, or both. Conclusions: This series of patients demonstrates the possibility that AML patients with IDH1 or IDH2 mutations benefit from the use of hypomethylating agents, and suggests it is worthwhile to prospectively investigate treatment of patients with IDH-mutated AML using hypomethylating agents.
Sequential liver and lung resection for colorectal cancer metastases: In which patients should surgery be proposed?
Authors: Muthukumarassamy Rajakannu, Pierre Magdeleinat, Eric Vibert, Pasquale F Innominato, Oriana Ciacio, Gabriella Pittau, Maximiliano Gelli, Antonio Sa Cunha, Daniel Cherqui, Francis Levi, Denis Castaing, Jean F. Morere, Rene Adam
Journal: Journal of Clinical Oncology (2015)

3524 Background: Resection of colorectal cancer (CRC) liver or lung metastases is an established therapeutic strategy. However, controversies exist when metastases are found concomitantly in both the organs or when the patients, who have undergone either liver or lung resection, have a recurrence in the other organ. Methods: All consecutive patients operated for CRC liver and lung metastasis (LLM) at our institution from January 1990 to December 2012 were reviewed. Our policy was to propose sequential surgery of both sites with perioperative chemotherapy, provided that the strategy was potentially curative. We aimed to evaluate Overall Survival (OS) of these patients, to develop a clinical usable prognostic score and to find out if cure is possible. Results: A total of 150 patients (89 men - 61 women; median age - 56 years) were included in the study. Median number of LLM resected was 3 and 1 respectively. Median follow-up was 5 years (Range 0.6 - 22.8 years). Median OS, 5-year OS and 10-year OS from first metastasis resection were 6 years, 59% and 35% respectively. Multivariate analysis identified metastatic CRC at initial diagnosis [P = 0.027], Pre-Lung resection CEA level > 100 ng/ml [P = 0.007], Pre-Lung resection CA19-9 level > normal [P = 0.029], Interval between 1st liver and 1st lung resection < 24 months [P = 0.004], > 2 lung metastases resected [P = 0.049] and Non-curative lung resection [P = 0.012] were independent predictors of OS. Simultaneous presentation of LLM and perioperative chemotherapy was not associated with OS. Prognostic model was developed using 5 preoperative factors. LLM score > 3 was associated with good 5-year survival [AUROC 0.7, Sensitivity 90%, Specificity 67%]. Fifteen patients were considered as cured with > 5 years disease-free survival from the last surgery (median LLM score 7). Conclusions: Good long-term survival can be achieved in patients who undergo sequential resection of the liver and lung metastases from CRC with 10% being cured. LLM score is an effective way to select patients for sequential resection. Higher the score better is the survival after sequential surgery and better is the chance of cure. Conversely, the role of surgery should be questioned in patients with LLM score < 3.
Predictive factors of tumor recurrence and death in patients with hepatocellular carcinoma treated by locoregional therapies: results of a retrospective cohort study
Authors: G. Gallo, P. Carucci, A. Veltri, A. Nascè, M. Diotallevi, M. Surace, E. Versino, S. Gaia, E. Rolle, G.M. Saracco
Journal: Journal of Hepatology (2017)
Tumor derived exsomes mediate tumor infiltrating NK-cell dysfunction in patients with hepatocellular carcinoma via TGF-β/SMAD pathway
Authors: Q.-F. Zhang, W.-W. Yin, Q. Liu, Y.-L. Li, M.-H. Li, J.-Y. Shao, Q.-F. He, H.-D. Hu, P. Hu, H. Ren, D.-Z. Zhang
Journal: Journal of Hepatology (2017)
Characterization of the cancer immune microenvironment of Mdr2(abcb4) -/- mice treated with diethylnitrosamine – a novel model close to human hepatocarcinogenesis
Authors: M.A. Qureshi, M. Ashfaq-Khan, M. Aslam, M.S. Senkowski, Y.O. Kim, T. Zimmermann, D. Schuppan
Journal: Journal of Hepatology (2017)
Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma
Authors: Pier Luigi Zinzani, Vincent Ribrag, Craig H. Moskowitz, Jean-Marie Michot, John Kuruvilla, Arun Balakumaran, Yayan Zhang, Sabine Chlosta, Margaret A. Shipp, Philippe Armand
Journal: Blood (2017)
Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial
Authors: Angela Alistar, Bonny B Morris, Rodwige Desnoyer, Heidi D Klepin, Keyanoosh Hosseinzadeh, Clancy Clark, Amy Cameron, John Leyendecker, Ralph D'Agostino, Umit Topaloglu, Lakmal W Boteju, Asela R Boteju, Rob Shorr, Zuzana Zachar, Paul M Bingham, Tamjeed Ahmed, Sandrine Crane, Riddhishkumar Shah, John J Migliano, Timothy S Pardee, Lance Miller, Gregory Hawkins, Guangxu Jin, Wei Zhang, Boris Pasche
Journal: The Lancet Oncology (2017)
DC-SIGN polymorphisms associate with sexual hepatitis C virus transmission and DC-SIGN m-RNA expression levels
Authors: G.S. Steba, S.M. Koekkoek, J.W. Vanhommerig, K. Brinkman, J.T.M. van der Meer, M. Prins, W.A. Paxton, R. Molenkamp, J. Schinkel
Journal: Journal of Hepatology (2017)
Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs
Authors: Atsuko Ohkubo, Tomomi Chida, Hidetomo Kikuchi, Tadashi Tsuda, Katsuyoshi Sunaga
Journal: Asian Journal of Pharmaceutical Sciences (2017)

We previously demonstrated that tomato juice (TJ) contains potent mechanism-based inhibitor(s) of CYP3A4. In this study, we investigated the effects of TJ and grapefruit juice (GFJ) on the pharmacokinetics of the CYP3A4-substrate drugs, nifedipine (NFP) and midazolam (MDZ), in male Wistar rats. Oral administration of GFJ 90 min before the intraduodenal administration of NFP or MDZ increased the area under the concentration–time curves (AUCs) of NFP and MDZ by 32.4% and 89.4%, respectively. TJ increased MDZ blood concentrations and AUC after intraduodenal MDZ administration; however, it had no effect on NFP. When MDZ and NFP were intravenously administered, GFJ significantly increased the AUC of MDZ, but only slightly increased that of NFP. In contrast, TJ only slightly increased the AUC of MDZ. These results suggest that, similar to GFJ, TJ influences the pharmacokinetics of CYP3A4-substrate drugs; however, it may be a drug-dependent partial effect.
Genome-Wide DNA Methylation Profiling Reveals Epigenetic Adaptation of Stickleback to Marine and Freshwater Conditions
Authors: Artem V. Artemov, Nikolai S. Mugue, Sergey M. Rastorguev, Svetlana Zhenilo, Alexander M. Mazur, Svetlana V. Tsygankova, Eugenia S. Boulygina, Daria Kaplun, Artem V. Nedoluzhko, Yulia A. Medvedeva, Egor B. Prokhortchouk
Journal: Molecular Biology and Evolution (2017)

The three-spined stickleback (Gasterosteus aculeatus) represents a convenient model to study microevolution-adaptation to a freshwater environment. Although genetic adaptations to freshwater environments are well-studied, epigenetic adaptations have attracted little attention. In this work, we investigated the role of DNA methylation in the adaptation of the marine stickleback population to freshwater conditions. DNA methylation profiling was performed in marine and freshwater populations of sticklebacks, as well as in marine sticklebacks placed into a freshwater environment and freshwater sticklebacks placed into seawater. We showed that the DNA methylation profile after placing a marine stickleback into fresh water partially converged to that of a freshwater stickleback. For six genes including ATP4A ion pump and NELL1, believed to be involved in skeletal ossification, we demonstrated similar changes in DNA methylation in both evolutionary and short-term adaptation. This suggested that an immediate epigenetic response to freshwater conditions can be maintained in freshwater population. Interestingly, we observed enhanced epigenetic plasticity in freshwater sticklebacks that may serve as a compensatory regulatory mechanism for the lack of genetic variation in the freshwater population. For the first time, we demonstrated that genes encoding ion channels KCND3, CACNA1FB, and ATP4A were differentially methylated between the marine and the freshwater populations. Other genes encoding ion channels were previously reported to be under selection in freshwater populations. Nevertheless, the genes that harbor genetic and epigenetic changes were not the same, suggesting that epigenetic adaptation is a complementary mechanism to selection of genetic variants favorable for freshwater environment.
Medical Marijuana and Marijuana Legalization
Authors: Rosalie Liccardo Pacula, Rosanna Smart
Journal: Annual Review of Clinical Psychology (2017)

State-level marijuana liberalization policies have been evolving for the past five decades, and yet the overall scientific evidence of the impact of these policies is widely believed to be inconclusive. In this review we summarize some of the key limitations of the studies evaluating the effects of decriminalization and medical marijuana laws on marijuana use, highlighting their inconsistencies in terms of the heterogeneity of policies, the timing of the evaluations, and the measures of use being considered. We suggest that the heterogeneity in the responsiveness of different populations to particular laws is important for interpreting the mixed findings from the literature, and we highlight the limitations of the existing literature in providing clear insights into the probable effects of marijuana legalization.
OUP accepted manuscript
Authors: Barend A van den Beukel, Roy de Ree, Suzanne van Leuven, Erica A Bakkum, Chema Strik, Harry van Goor, Richard P G Ten Broek
Journal: Human Reproduction Update (2017)

Chronic pain is a frequent post-operative complication, affecting ~20–40% of patients who have undergone surgery of the female genital or alimentary tract. Chronic pain is an important risk factor for diminished quality of life after surgery. Adhesions are frequently associated with chronic post-operative pain; however, surgical treatment of adhesion-related pain is controversial. The aim of this study was to investigate the efficacy and harms of surgical interventions for chronic post-operative pain attributable to adhesions. A search was conducted using PubMed, EMBASE and CENTRAL, without restrictions pertaining to date, publication status or language. Randomized trials and cohort studies from all surgical interventions for chronic post-operative pain were considered eligible. Patients with a concomitant diagnosis that could cause chronic pain (e.g. endometriosis or inflammatory conditions) were excluded. Outcome measures were graded according to clinical relevance, with improvement of pain at long-term follow-up regarded as most clinically relevant. A total of 4294 unique citations were identified, of which 13 studies met the criteria for inclusion. Two of the analysed studies were randomized trials, of which one had a low risk of bias. Only one trial, randomizing between laparoscopic adhesiolysis without an adhesion barrier and diagnostic laparoscopy, reported improvement of pain at long-term follow-up. In this trial, pain improved in 55.8% of patients after adhesiolysis and in 41.7% of patients in the control group; however, the difference was not significant (relative risk (RR) 1.34; 95% CI: 0.89–2.02). Most non-randomized studies had mid-length follow-up (6–12 months). In pooled analyses of trials and non-randomized studies, improvement of pain was reported in 72% of patients who underwent adhesiolysis (95% CI: 61–83%) at any follow-up longer than 3 months. The incidence of negative laparoscopies was 20% (95% CI: 10–30%). The overall incidence of complications following laparoscopic adhesiolysis was 4% (95% CI: 1–6%). Laparoscopic adhesiolysis reduces pain from adhesions in ~70% of patients in the initial phase after treatment. However, there is little evidence for long-term efficacy of adhesiolysis for chronic pain. Other drawbacks of laparoscopic adhesiolysis are the high rate of negative laparoscopies and the risk of bowel injury. At present, there is little evidence to support routine use of adhesiolysis in treatment for chronic pain. New research is needed to investigate whether the results of adhesiolysis can be improved with new techniques for diagnosis and prevention of adhesion reformation.