tbuckley/cabot-search huggingface dataset:
Usefulness of the ‘two‐step method’ of digital follow‐up for early‐stage melanoma detection in high‐risk French patients: a retrospective 4‐year study
Authors: G. Gasparini, N. Madjlessi, J. Delyon, L. Carmisciano, N. Brahimi, N. Basset‐Seguin, M. Oren, M. Battistella, C. Lebbé, F. Herms, B. Baroudjian
Journal: British Journal of Dermatology (2019)
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Authors: Vlado Perkovic, Meg J. Jardine, Bruce Neal, Severine Bompoint, Hiddo J.L. Heerspink, David M. Charytan, Robert Edwards, Rajiv Agarwal, George Bakris, Scott Bull, Christopher P. Cannon, George Capuano, Pei-Ling Chu, Dick de Zeeuw, Tom Greene, Adeera Levin, Carol Pollock, David C. Wheeler, Yshai Yavin, Hong Zhang, Bernard Zinman, Gary Meininger, Barry M. Brenner, Kenneth W. Mahaffey
Journal: New England Journal of Medicine (2019)

Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
Pills or public health?
Authors: Fiona Godlee
Journal: BMJ (2019)

How best to tackle the rising tide of non-communicable disease linked to lifestyle, or, more accurately, linked to the environments in which people live? With pills or with traditional public health interventions: healthier food and cleaner air?

The push for pills is strong. As reported by the Science Media Centre, the expert response to NICE’s draft guideline on hypertension has been glowing (http://bit.ly/2IjMEgD). NICE wants to lower the threshold for starting treatment for mild hypertension. All six experts (of whom two declare industry ties and three give no statement of interests …
Autophagy inhibition potentiates the anti-angiogenic property of multikinase inhibitor anlotinib through JAK2/STAT3/VEGFA signaling in non-small cell lung cancer cells
Authors: L. Liang, K. Hui, C. Hu, Y. Wen, X. Jiang
Journal: Annals of Oncology (2019)

Background: The efficacy and safety of multikinase inhibitor anlotinib has been confirmed in the treatment of advanced non-small cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by anlotinib were not fully elucidated, and the underlying mechanisms related to resistance remains largely elusive. Methods: Cell viability, colony formation, apoptosis and tumor growth assays were performed to examine the effect of anlotinib on lung cancer cells in vitro and in vivo. The punctate patterns of LC3-I/II were detected by confocal microscopy. HUVECs migration was detected using Transwell and scratch wound-healing assay. To visualize the microvessels, tublar formation assay was performed. The expression of LC3-I/II and beclin-1 and the changes of JAK2/STAT3/VEGFA pathway were detected by western blotting. The VEGFA levels in tumor supernatant were measured by ELISA. Results: Anlotinib treatment decreased cell viability and induced apoptosis in Calu-1 and A549 cells. Moreover, anlotinib induced human lung cancer cell autophagy in a dose- and time-dependent manner. Blocking autophagy enhanced the cytotoxicity and anti-angiogenic ability of anlotinib as evidenced by HUVECs migration, invasion, and tublar formation assay. Co-administration of anlotinib and chloroquine (CQ) further reduced VEGFA level in the tumor supernatant, compared with that of anlotinib or CQ treatment alone. When autophagy was induced by rapamycin, the JAK2/STAT3 pathway was activated and VEGFA was elevated, which was attenuated after deactivating STAT3 by S3I-201. Further in vivo studies showed that anlotinib inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3/VEGFA pathway, and CQ enhanced this effect. Conclusions: Anlotinib induced apoptosis and protective autophagy in human lung cancer cell lines. Autophagy inhibition further enhanced the cytotoxic effects of anlotinib, and potentiated the anti-angiogenic property of anlotinib through JAK2/STAT3/VEGFA signaling. Legal entity responsible for the study: The authors. Funding: National Natural Science Foundation of China grants 81472792 and Postgraduate Research & Practice Innovation Program of Jiangsu Province grants SJCX18_0707. Disclosure: All authors have declared no conflicts of interest.
Some patient interventions increased thiazide prescriptions and improved blood pressure control
Authors: Ann Marie Navar
Journal: Annals of Internal Medicine (2019)

Source Citation Kaboli P, Howren MB, Ishani A, et al. Efficacy of patient activation interventions with or without financial incentives to promote prescribing of thiazides and hypertension control: a randomized clinical trial. JAMA Network Open. 2018;1:e185017.
Activation of the Unfolded Protein Response via Inhibition of Protein Disulfide Isomerase Decreases the Capacity for DNA Repair to Sensitize Glioblastoma to Radiotherapy
Authors: Yajing Liu, Wenbin Ji, Andrea Shergalis, Jiaqi Xu, Amy M. Delaney, Andrew Calcaterra, Anupama Pal, Mats Ljungman, Nouri Neamati, Alnawaz Rehemtulla
Journal: Cancer Research (2019)

Abstract Patients with glioblastoma multiforme (GBM) survive on average 12 to 14 months after diagnosis despite surgical resection followed by radiotheraphy and temozolomide therapy. Intrinsic or acquired resistance to chemo- and radiotherapy is common and contributes to a high rate of recurrence. To investigate the therapeutic potential of protein disulfide isomerase (PDI) as a target to overcome resistance to chemoradiation, we developed a GBM tumor model wherein conditional genetic ablation of prolyl 4-hydroxylase subunit beta (P4HB), the gene that encodes PDI, can be accomplished. Loss of PDI expression induced the unfolded protein response (UPR) and decreased cell survival in two independent GBM models. Nascent RNA Bru-seq analysis of PDI-depleted cells revealed a decrease in transcription of genes involved in DNA repair and cell-cycle regulation. Activation of the UPR also led to a robust decrease in RAD51 protein expression as a result of its ubiquitination-mediated proteosomal degradation. Clonogenic survival assays demonstrated enhanced killing of GBM cells in response to a combination of PDI knockdown and ionizing radiation (IR) compared with either modality alone, which correlated with a decreased capacity to repair IR-induced DNA damage. Synergistic tumor control was also observed with the combination of PDI inhibition and IR in a mouse xenograft model compared with either single agent alone. These findings provide a strong rationale for the development of PDI inhibitors and their use in combination with DNA damage-inducing, standard-of-care therapies such as IR. Significance: These findings identify PDIA1 as a therapeutic target in GBM by demonstrating efficacy of its inhibition in combination with radiotherapy through a novel mechanism involving downregulation of DNA repair genes.
Surgery in reference centers improves survival of sarcoma patients: a nationwide study
Authors: J.-Y. Blay, C. Honoré, E. Stoeckle, P. Meeus, M. Jafari, F. Gouin, P. Anract, G. Ferron, A. Rochwerger, M. Ropars, S. Carrere, F. Marchal, F. Sirveaux, A. Di Marco, L.R. Le Nail, J. Guiramand, G. Vaz, J.-C. Machiavello, O. Marco, S. Causeret, P. Gimbergues, F. Fiorenza, L. Chaigneau, F. Guillemin, J.-M. Guilloit, F. Dujardin, J.-P. Spano, J.-C. Ruzic, A. Michot, P. Soibinet, E. Bompas, C. Chevreau, F. Duffaud, M. Rios, C. Perrin, N. Firmin, F. Bertucci, C. Le Pechoux, F. Le Loarer, O. Collard, M. Karanian-Philippe, M. Brahmi, A. Dufresne, A. Dupré, F. Ducimetière, A. Giraud, D. Pérol, M. Toulmonde, I. Ray-Coquard, A. Italiano, A. Le Cesne, N. Penel, S. Bonvalot
Journal: Annals of Oncology (2019)

NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry.
SAT-123-Serum Mac-2 binding protein glycosylation isomer and handgrip strength correlate with serum myostatin level in chronic liver disease
Authors: Tomoyuki Suehiro, Yuki Kugiyama, Shigemune Bekki, Satoru Hashimoto, Akira Saeki, Shinya Nagaoka, Seigou Abiru, Kazumi Yamasaki, Atsumasa Komori, Hiroshi Yatsuhashi
Journal: Journal of Hepatology (2019)
SAT-265-Anti-VHC therapy does not increase de risk of developing splanchnic vein thrombosis in patients with cirrhosis
Authors: Fanny Turon, Claudia Berbel, Sabela Lens, Anna Baiges, José Ferrusquia, Marta Magaz, Zoe Mariño, Virginia Hernandez-Gea, Garcia Pagan Juan Carlos
Journal: Journal of Hepatology (2019)
The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes
Authors: Bon Ham Yip, Violetta Steeples, Emmanouela Repapi, Richard N. Armstrong, Miriam Llorian, Swagata Roy, Jacqueline Shaw, Hamid Dolatshad, Stephen Taylor, Amit Verma, Matthias Bartenstein, Paresh Vyas, Nicholas C.P. Cross, Luca Malcovati, Mario Cazzola, Eva Hellström-Lindberg, Seishi Ogawa, Christopher W.J. Smith, Andrea Pellagatti, Jacqueline Boultwood
Journal: Journal of Clinical Investigation (2017)

In Figure 4D, the horizontal axes of the two graphs were labeled incorrectly, and one sentence in the legend for this part was also incorrect.The correct figure part and sentence are below.Expression of H2AFY isoform 1.1 and the STRAP long isoform in U2AF1 S34F and U2AF1 WT transduced cells was measured by isoform-specific qRT-PCR relative to the EV control (red bars: erythroid cells; blue bars: granulomonocytic cells).
What's hot that the other lot got
Authors: J Elshof
Journal: Thorax (2019)

Nasal high-flow (NHF) therapy has been shown to be a beneficial therapy for patients with acute respiratory failure in hospital and might be beneficial in patients with chronic hypoxemic respiratory failure if delivered at home. Storgaard et al . ( Int J Chron Obstruct Pulmon Dis 2018;13:1195 ) performed a randomised controlled trial comparing NHF added to long-term oxygen therapy (LTOT+NHF) to LTOT alone in 200 moderately severe COPD patients. Compared with the previous year, patient-reported exacerbations increased from 2.90 to 4.95/patient/year in the LTOT alone group compared with a slight decrease from 3.23 to 3.12/patient/year in the LTOT+NHF group, resulting in a lower exacerbation frequency in the NHF group compared with the LTOT group (p<0.001). However, hospital admission and all-cause mortality were not different between the groups after 1 year. Exploratory analyses suggested that there was a dose response effect with a reduction in admissions in patients with high device usage. Furthermore, dyspnoea symptoms, health-related quality of life, arterial carbon dioxide pressure (PaCO2), and the 6 min walking distance improved in the NHF group compared with the LTOT group (all p<0.001). The study demonstrates that NHF is a potentially viable therapy in the home setting and may have physiological and clinical impact in patients with COPD on LTOT. Future studies should focus on high …
Evaluation of brain-derived neurotrophic factor (BDNF) genetic polymorphism (rs6265) on chemotherapy-associated cognitive impairment in early-stage breast cancer (ESBC) patients.
Authors: Terence NG, Shu Mei Jessie Teo, Hui Ling Angie Yeo, Maung Shwe, Yan Xiang Gan, Yin Ting Cheung, Yee Pin Tan, Wei Sean Yong, Preetha Madhukumar, Kiley Wei-Jen Loh, Si-Lin Koo, Amit Jain, Guek Eng Lee, Mabel Wong, Rebecca Alexandra Dent, Yoon Sim Yap, Raymond C.H. Ng, Chiea Chuen Khor, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2015)

9616 Background: BDNF is a neurotrophin that regulates neuronal function and development, which is implicated in several neurodegenerative conditions. There is preliminary data to suggest that the reduction of BDNF concentrations may lead to post-chemotherapy cognitive impairment. We hypothesized that a single nucleotide polymorphism (rs6265) of the BDNF gene may down-regulate BDNF levels, predisposing certain patients with cognitive impairment. This study was designed to evaluate the impact of BDNF gene polymorphism on chemotherapy-associated cognitive impairment. Methods: Overall, 145 chemotherapy receiving ESBC patients (mean age: 50.8 ± 8.8 years; 82.1% Chinese) were recruited between 2011 and 2014. Patients' self-perceived cognitive function were assessed longitudinally over three time points, using the validated FACT-Cog (v.3) to examine six cognitive domains: concentration, functional interference, memory, mental acuity, multitasking ability and verbal fluency. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between BDNF Val66Met polymorphism and cognition, adjusting for ethnicity and clinically important covariates. Results: 54 (37%) patients reported cognitive impairment post-chemotherapy. 38 (26.2%) patients were homozygous for Val/Val, 74 (51.0%) were heterozygous for Val/Met, and 33 (22.8%) were homozygous for Met/Met without deviation from the Hardy-Weinberg equilibrium (p > 0.05). The BDNF Met/Met genotype was associated with statistically significantly lower odds of developing cognitive impairment (OR = 0.26, 95% CI: 0.08-0.92, p = 0.036). Furthermore, the Met-carriers were less likely to experience impairment in the verbal fluency (OR = 0.34, 95% CI: 0.12-0.90, p = 0.031) and multitasking ability (OR = 0.37, 95% CI: 0.15-0.91, p = 0.030) domains, comparing to the Val/Val homozygote. Conclusions: This is the first study to provide evidence that carriers of the BDNF Met allele are protective against chemotherapy-associated cognitive impairment. Further validation studies are required to confirm the findings.
SAT-253-Impact of HCV clearance on HCC development and patient survival: Propensity score-matched analysis of an ongoing database of 2173 CHC patients
Authors: Mina Nakagawa, Yasuhiro Asahina, Jun Tsuchiya, Ayako Sato, Tomoyuki Tsunoda, Masato Miyoshi, Emi Inoue, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Makoto Tomita, Mamoru Watanabe
Journal: Journal of Hepatology (2019)
Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in <i>GLS</i>
Authors: André B.P. van Kuilenburg, Maja Tarailo-Graovac, Phillip A. Richmond, Britt I. Drögemöller, Mahmoud A. Pouladi, René Leen, Koroboshka Brand-Arzamendi, Doreen Dobritzsch, Egor Dolzhenko, Michael A. Eberle, Bruce Hayward, Meaghan J. Jones, Farhad Karbassi, Michael S. Kobor, Janet Koster, Daman Kumari, Meng Li, Julia MacIsaac, Cassandra McDonald, Judith Meijer, Charlotte Nguyen, Indhu-Shree Rajan-Babu, Stephen W. Scherer, Bernice Sim, Brett Trost, Laura A. Tseng, Marjolein Turkenburg, Joke J.F.A. van Vugt, Jan H. Veldink, Jagdeep S. Walia, Youdong Wang, Michel van Weeghel, Galen E.B. Wright, Xiaohong Xu, Ryan K.C. Yuen, Jinqiu Zhang, Colin J. Ross, Wyeth W. Wasserman, Michael T. Geraghty, Saikat Santra, Ronald J.A. Wanders, Xiao-Yan Wen, Hans R. Waterham, Karen Usdin, Clara D.M. van Karnebeek
Journal: New England Journal of Medicine (2019)

We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5' untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
Clinical response correlates with 4‐week postinjection ustekinumab concentrations in patients with moderate‐to‐severe psoriasis
Authors: N. Van den Berghe, E. De Keyser, R. Soenen, L. Meuleman, S. Lanssens, A. Gils, J. Lambert
Journal: British Journal of Dermatology (2019)

Cost-effective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decision-making. A concentration-response relationship for ustekinumab at trough is uncertain owing to the contradictory results reported.To investigate the relationship between 4-week postinjection ustekinumab concentrations and clinical response in patients with psoriasis.Forty-nine patients with moderate-to-severe psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for ≥ 16 weeks were included. Ustekinumab serum concentrations and anti-ustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI).At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 μg mL-1 (ρ = -0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI ≤ 2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 μg mL-1 , P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 μg mL-1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had anti-ustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively).A concentration-response relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4-week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization. What's already known about this topic? Monitoring drug concentrations is a valuable tool that can guide clinical decision-making when drug concentrations are linked to clinical outcomes. The presence of a concentration-response relationship for ustekinumab at trough is still debated owing to the contradictory results reported. What does this study add? A concentration-response relationship at week 4 after injection for ustekinumab-treated patients with psoriasis was demonstrated. Monitoring 4-week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization. Based on the findings of this study, a treatment algorithm for patients with a suboptimal response is proposed.
FRI-179-Antiviral therapy might not be required for chronic hepatitis B patients in the immune-tolerant phase with a significantly low incidence rate of liver-related events
Authors: Mi Young Jeon, Tae Seop Lim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Beom Kyung Kim, Seung Up Kim
Journal: Journal of Hepatology (2019)
Abstract 12759: Utilization of Cardiac Rehabilitation Among Patients With Heart Failure
Authors: Linda G Park, David W Schopfer, Ning Zhang, Hui Shen, Chris Vercammen, Mary A Whooley
Journal: Circulation (2016)

Introduction: Cardiac rehabilitation (CR) is linked to reduced mortality and morbidity including improvements in cardiorespiratory fitness, psychosocial state, and quality of life in patients with heart failure (HF). However, little is known about CR utilization among patients with HF. We sought to determine: a) the proportion of patients with HF who participated in CR during a 5-year period; and b) patient characteristics associated with participation. Methods: A retrospective study was conducted using national data from the Centers for Medicare &amp; Medicaid Services (CMS 5% random sample) and the Veterans Health Administration (VA) Healthcare System. We used primary discharge ICD-9 codes to identify all patients hospitalized for HF between 1/2007 and 12/2011. After excluding patients who died within 30 days of hospitalization, we identified participation in CR programs using CPT codes from Medicare and VA claims data. Multivariate logistic regression was used to identify patient characteristics independently associated with CR participation. Results: During the five-year study period, 66,710 Veteran patients and 243,208 of the 5% Medicare sample were hospitalized for HF. Of these, 1,554 Veterans (2.3%) and 6,280 Medicare beneficiaries (2.6%) attended one or more sessions of outpatient CR. Among Medicare beneficiaries, men were more likely than women to participate in CR (3.7% vs. 1.8%; p&lt;0.001), but there was no gender difference in Veterans (2.3% vs. 2.8%; p=0.40). Characteristics associated with participation in CR among both VA and CMS patients included younger age, white race, and history of ischemic heart disease. Chronic conditions such as diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and depression were associated with lower participation in CR. Conclusions: Very few HF patients participated in CR between 2007 and 2011, but participation was especially low among older, non-white women with a history of depression or other chronic medical conditions. Since Medicare has recently introduced coverage for CR in patients with systolic HF, we must increase efforts to improve CR participation, especially among these vulnerable groups.
Blood Lead Screening and the Ongoing Challenge of Preventing Children’s Exposure to Lead
Authors: Michael Weitzman
Journal: JAMA Pediatrics (2019)

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Author Correction: Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours
Authors: Han Yao, Jiang Lan, Chushu Li, Hubing Shi, Jean-Philippe Brosseau, Huanbin Wang, Haojie Lu, Caiyun Fang, Yao Zhang, Lunxi Liang, Xiaolin Zhou, Chaojun Wang, Yu Xue, Yun Cui, Jie Xu
Journal: Nature Biomedical Engineering (2019)
SAT-287-A novel non-invasive index based on extracellular matrix markers can identify NAFLD patients with active disease and significant fibrosis: analysis of the CENTAUR study
Authors: Samuel Daniels, Sophie Birot, Diana Leeming, Mette Juul Nielsen, Andrew Mckibben, Sean Muthian, Eduardo Bruno Martins, Star Seyedkazemi, Laurent Fischer, Morten Karsdal
Journal: Journal of Hepatology (2019)