tbuckley/cabot-search huggingface dataset:
Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca
Authors: Xueming Zhang, Ningyan Yang, Xiaojing Liu, Jiazeng Su, Xin Cong, Liling Wu, Yan Zhang, Guangyan Yu
Journal: International Journal of Oral Science (2018)

Abstract Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients’ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.
Prognostic relevance of primary tumor location in stage III and II colon cancer: Experience at University Hospital Ramon y Cajal (HURyC) Madrid.
Authors: Arantzazu Martínez Barquín García, Olga Martinez Saez, Juan José Serrano Domingo, Roberto Martín Huertas, Maria Villamayor Delgado, Cristina Saavedra Serrano, Elena Corral de la Fuente, Pablo Reguera Puertas, FEDERICO LONGO, Vanesa Pachón Olmos, Mercedes Rodríguez Garrote, Carmen Guillen, Alfredo Carrato, REYES Ferreiro
Journal: Journal of Clinical Oncology (2018)

703 Background: Primary tumor location of colon cancer (CC) is emerging as an important prognostic factor owing to distinct biological features. However, this factor still does not represent a prognostic parameter when deciding for adyuvant or palliative chemotherapy. In a meta-analysis of 66 studies including patients with all stages of disease, left-sided primary tumor location was associated with a significantly reduced risk of death and this was independent of other prognostic factors. Methods: We retrospectively included patients with stage II and III CC that underwent surgical resection between 2009 and 2014 HURyC. We performed a multivariate Cox model analysis to estimate if tumor location is an independent prognostic factor for overall survival (OS). The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes ( &lt; 12 or ≥ 12), perforation, grade, use of adyuvant chemotherapy and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied &gt; 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (267 left sided and 297 right sided). The median follow-up of the entire cohort was 49 months. Globally, right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.74, p: 0.128; HR: 0.94, p: 0.75, respectively). By stages, stage II right sided CC seemed to show better DFS (HR: 0.45, p: 0.02), although no significant differences were found in OS (HR: 1.004, p: 0.98). Stage III right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.87, p: 0.585; HR: 0.66, p: 0.19, respectively). Conclusions: The multivariate analysis did not show significant differences in terms of prognostic relevance of primary tumor location in the adyuvant setting.
Identification of a stable HBV inter-genotype (A/G) recombinant strain in a guinean patient in “grey zone” of treatment
Authors: A.I. Gil, A. Madejón, I. Francisco-Recuero, E. Villafranca, M. Romero, A. García-Sánchez, A.O. Martin, J.C. Erdozaín, P. Castillo, R. Mena, F.J.G.-S. Rey
Journal: Journal of Hepatology (2018)
Deep immunophenotyping of liver infiltrating lymphocytes reveals distinct differences in the T cell compartment of patients with primary sclerosing cholangitis
Authors: T. Poch, L. Glau, A. Langeneckert, L. Hess, W. Salzberger, G. Martrus, S. Lunemann, D. Schwinge, M. Koch, L. Fischer, K. Oldhafer, M. Altfeld, A. Lohse, E. Tolosa, C. Schramm
Journal: Journal of Hepatology (2018)
Second-line treatment of modified FOLFIRINOX or nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma.
Authors: Masato Ozaka, Takashi Sasaki, Ikuhiro Yamada, Ryo Kanata, Dai Akiyama, Tomoko Katagiri, Koichi Takano, Masato Matsuyama, Naoki Sasahira
Journal: Journal of Clinical Oncology (2018)

458 Background: Both FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine(GnP) standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for second-line treatments for MPA. The aim of this study was to compare second-line modified FFX (mFFX) after GnP failure with second-line GnP after mFFX failure. Methods: From January 2015 to Jul 2017, medical records were retrospectively reviewed for consecutive patients receiving mFFX or GnP for a histologically proven MPA after failure of GnP or mFFX respectively. Patients were treated with mFFX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU) or GnP (Gemcitabine 1000 mg/m2/, nab-paclitaxel 125mg/m2 d1,8 15) until disease progression, patient refusal or unacceptable toxicity. Results: Second-line mFFX was administered to 50 patients and GnP was 25 patients. At baseline of second-line treatment, there was no difference in patient’s characteristics between mFFX group and GnP group. No significant difference in the response rate (mFFX, 16.6% vs. GnP, 10.5%, P = 0.63) or the disease control rate (mFFX, 50% vs. GnP, 64%, P = 0.82) was seen between the two groups. Median Progression free survival of GnP/mFFx were 4.3 months/4.6 months (p=0.89) and median survival (OS) from the 2nd line treatment of GnP/mFFx were 10.4 months/10.8 months (p=0.65) and OS from the first-line treatment of GnP/mFFx were 20.6 months/16.5 months (p=0.34). No toxic death occurred in both groups. There was no difference in the incident of adverse event between mFFX group and GnP group. Conclusions: Second-line mFFX and GnP achieved similar disease control and survival in unresectable pancreatic cancer. The use of the FFX and GnP in sequence is an attractive option to maximize disease control and survival. We need the clinical trial to compare with mFFX and GnP in sequence to guide the selection of initial chemotherapy.
Magnet-assisted diverticuloplasty for treatment of Zenker’s diverticulum
Authors: Liansong Ye, Hongze Zeng, Shuifang Wang, Jingsun Jiang, Hong Tang, Chuanhui Li, Bing Hu
Journal: Endoscopy (2018)

A 48-year-old man presented with a 1-year history of progressive dysphagia and regurgitation. Esophagography and upper endoscopy demonstrated a Zenker's diverticulum 18 cm from the incisors ([Fig. 1]). Endoscopic diverticulotomy was performed, but, after 5 months, the diverticulum had not disappeared ([Fig. 2]). Inspired by widespread use of magnets in the gastrointestinal tract in recent years [1], we performed a magnet-assisted diverticuloplasty (MAD) ([Video 1]).
Functional relevance and pro-fibrogenic properties of mucosal-associated invariant T cells (MAIT) during chronic liver diseases
Authors: P. Hegde, E. Weiss, Valérie Paradis, J. Wan, M. Mabire, S. Sukriti, P.-E. Rautou, M. Albuquerque, O. Picq, A. Gupta, G. Ferrere, Hélène Gilgenkrantz, B. Kiaf, A. Toubal, L. Beaudoin, P. Letteron, R. Moreau, A. Lehuen, S. Lotersztajn
Journal: Journal of Hepatology (2018)
Effet of bariatric surgery in biopsy-proven NASH patients after 5 years
Authors: G. Lassailly, C. Robert, V. Gnemmi, A. Louvet, L. Emmanuelle, F. Artru, M. Ningarhari, Valérie Canva, S. Dharancy, F. Pattou, P. Mathurin
Journal: Journal of Hepatology (2018)
New insights in Transforming Growth Factor Beta signalling pathway on tumor suppression and metastatic potential in primary liver cancer
Authors: S. Pereira, L. Rodrigues, D. Castven, F. Mahn, P. Galle, J. Marquardt, S. Dooley, N.M. Beinker, D. Strand, H. Lang, P. Grimminger
Journal: Journal of Hepatology (2018)
The ENABLE projects: Consistent high prevalence of undiagnosed active blood borne virus infection [HBV, HCV, HIV] across four urban emergency departments in England – Data for action?
Authors: M. Hopkins, S. Todd, M. Beadsworth, R. Vivancos, C. Anderson, D. Muir, Z. Mohamed, A. Brown, A. Guleri, R. Sharma, R. Palmer, D. Singleton, M. Ruf, A. Chawla
Journal: Journal of Hepatology (2018)
The antiretroviral rilpivirine induces hepatic regeneration in liver fibrosis and cirrhosis by modulating the STAT3/STAT1 balance
Authors: A. Martí-Rodrigo, Ángela B. Moragrega, P. Martí-Rodrigo, D. Castelli, N. Apostolova, Juan V. Esplugues, A. Blas-García
Journal: Journal of Hepatology (2018)
Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins
Authors: Kausik K. Ray, Robert M. Stoekenbroek, David Kallend, Lawrence A. Leiter, Ulf Landmesser, R. Scott Wright, Peter Wijngaard, John J.P. Kastelein
Journal: Circulation (2018)

The ORION-1 trial (Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol [LDL-C]) demonstrated that inclisiran, an siRNA therapeutic that targets protease proprotein convertase subtilisin/kexin type 9 mRNA within hepatocytes, produces significant low-density lipoprotein cholesterol reduction. The effects of inclisiran on other lipids are less well described.ORION-1 was a phase 2 trial assessing 6 different inclisiran dosing regimens versus placebo. Participants with elevated low-density lipoprotein cholesterol despite receiving maximally tolerated statin therapy received a single-dose (200, 300, or 500 mg) or 2-dose starting regimen (100, 200, or 300 mg on days 1 and 90) of inclisiran or placebo. This prespecified analysis reports the percentage reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, very-low-density lipoprotein cholesterol, lipoprotein(a), triglycerides, HDL-C, and apo A1 at the primary efficacy time point (day 180) with mixed-effect models for repeated measures. Additional prespecified analyses report time course of changes from baseline at each visit to day 210, interindividual variation in response, and lipid goal attainment.The mean age of the 501 participants was 63 years, 65% were male, 69% had atherosclerotic cardiovascular disease, 73% used statins, and mean low-density lipoprotein cholesterol was 128 mg/dL. A single dose of inclisiran reduced apo B, non-HDL-C, and very-low-density lipoprotein cholesterol over 210 days. A second dose of inclisiran provided additional lowering of these lipids. At day 180, non-HDL-C was lowered dose-dependently: by 25% from 148±43 to 110±45 mg/dL in the 200-mg single-dose group and by 46% from 161±58 to 91±58 mg/dL in the 2-dose 300-mg group. For the same dosing regimens, apo B was reduced by 23% from 101±23 to 78±29 mg/dL and by 41% from 106±31 to 65±33 mg/dL ( P<0.001 for all groups versus placebo). In the 300-mg 2-dose group, all individuals experienced apo B and non-HDL-C reductions. There was larger interindividual variation in very-low-density lipoprotein cholesterol, triglycerides, and lipoprotein(a) reductions. In the 300-mg 2-dose group, the percentages of patients achieving guideline-recommended apo B goals for high- and very-high-risk patients at day 180 were 78% and 90%; 68% and 83% of participants achieved non-HDL-C <100 and <130 mg/dL.Inclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting the synthesis of protease proprotein convertase subtilisin/kexin type 9 through siRNA may be a viable alternative to other approaches that target protease proprotein convertase subtilisin/kexin type 9.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02597127.
The mineralocorticoid receptor as a modulator of innate immunity and atherosclerosis
Authors: Charlotte D C C van der Heijden, Jaap Deinum, Leo A B Joosten, Mihai G Netea, Niels P Riksen
Journal: Cardiovascular Research (2018)

The mineralocorticoid receptor (MR) is a member of the nuclear receptor steroid-binding family. The classical MR ligand aldosterone controls electrolyte and fluid homeostasis after binding in renal epithelial cells. However, more recent evidence suggests that activation of extrarenal MRs by aldosterone negatively impacts cardiovascular health independent of its effects on blood pressure: high levels of aldosterone associate with an increased cardiovascular event rate, where MR antagonists exert beneficial effects on cardiovascular mortality. The most important cause for cardiovascular events is atherosclerosis that is currently considered a low-grade inflammatory disorder of the arterial wall. In this inflammatory process, the innate immune system plays a deciding role, with the monocyte-derived macrophage being the most abundant cell in the atherosclerotic plaque. Intriguingly, both monocytes and macrophages express the MR, and a growing body of evidence shows that these cells are skewed into a pro-inflammatory and pro-atherosclerotic phenotype via MR stimulation. In this review, we detail the current perspective on the role of the monocyte and macrophage MR in atherosclerosis development and provide a comprehensive framework of the effects of MR activation of the innate immune system that might drive the pro-atherosclerotic outcome.
Abstract 2082: A Model of Quality of Life in Adolescents with Congenital Heart Disease
Authors: Ju Ryung Moon, Soo-ln Jeong, June Huh, I-Seok Kang, Seung Woo Park, Ji-Hyuk Yang, Tae-Gook Jun, Heung Jae Lee
Journal: Circulation (2008)

Objective : This study was examined to identify the variables related to quality of life (QOL) in adolescents with congenital heart disease (CHD). Methods : The subjects were 266 adolescents with CHD under observation following cardiac surgery in three cardiac centers in Korea. The adolescents each completed twenty questionnaires. The exogenous variables in the model were individual risk factors, individual protective factors, family protective factors and social protective factors, while QOL and resilience were an endogenous variable. These six theoretical variables were assessed by 20 measurable variables (anxiety, depression, symptom distress, NYHA Functional class, oxygen saturation, number of operations, self-esteem, hope, attitude toward CHD, body image, academic achievement, family cohesion, family function, parental support, parental overprotection, socioeconomic status, friend support, teacher support, resilience and QOL) and 15 paths were established. Data were analysed using structural equation modelling. Results: The overall fit indices of the hypothetical model were χ2=26.63, GFI=.96, RMR=.02, NFI=.95, RFI=.85, IFI=.98 and PNFI=.87. All 15 paths in the hypothetical model were found to be significant(all, p&lt;0.01). Higher resilience (t=11.93), family (t=7.88), individual (t=5.75), and social (t=4.14) protective factors were associated with increased QOL, as were lower individual risk factors (t=−5.30). Resilience had the greatest impact on QOL. Individual protective factors correlated positively with both family (t=8.88) and social (t=8.33) protective factors, while family factors correlated positively with social protective factors (t=9.31). Individual risk factors correlated negatively with family (t=−7.13), individual (t=−7.00) and social (t=−4.69) protective factors. Thus, the higher each of these protective factors was, the smaller the effect of individual risk factors. Conclusion: To increase the QOL of adolescents with CHD, it is important to develop a strategy to increase resilience. Furthermore, nursing interventions that will enhance individual, family, and social protective factors must be developed and implemented in order to reduce the negative effects of individual risk factors.
Cardiovascular Effects of New Oral Glucose-Lowering Agents
Authors: André J. Scheen
Journal: Circulation Research (2018)

Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, and initial data from phase 2 to 3 clinical trials suggested a reduction in major cardiovascular events. However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk. An unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. SGLT-2 inhibitors (gliflozins) promote glucosuria, thus reducing glucose toxicity and body weight, and enhance natriuresis, thus lowering blood pressure. Two CV outcome trials in type 2 diabetes mellitus patients mainly in secondary prevention showed remarkable positive results. Empagliflozin in EMPA-REG-OUTCOME (EMPAgliflozin Cardiovascular OUTCOME Events in Type 2 Diabetes Mellitus Patients) reduced major cardiovascular events, CV mortality, all-cause mortality, and hospitalization for heart failure. In CANVAS (Canagliflozin Cardiovascular Assessment Study), the reduction in CV mortality with canagliflozin failed to reach statistical significance despite a similar reduction in major cardiovascular events. The underlying protective mechanisms of SGLT-2 inhibitors remain unknown and both hemodynamic and metabolic explanations have been proposed. CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes.
Author Correction: L1-associated genomic regions are deleted in somatic cells of the healthy human brain
Authors: Jennifer A Erwin, Apuã C M Paquola, Tatjana Singer, Iryna Gallina, Mark Novotny, Carolina Quayle, Tracy A Bedrosian, Francisco I A Alves, Cheyenne R Butcher, Joseph R Herdy, Anindita Sarkar, Roger S Lasken, Alysson R Muotri, Fred H Gage
Journal: Nature Neuroscience (2018)
Afatinib in Osimertinib-Resistant EGFR ex19del/T790M/P794L Mutated NSCLC
Authors: Léon C. van Kempen, Hangjun Wang, Maria Leonor Aguirre, Alan Spatz, Goulnar Kasymjanova, Juliana F. Vilacha, Matthew R. Groves, Jason Agulnik, David Small
Journal: Journal of Thoracic Oncology (2018)
Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma
Authors: K.A. Su, L.A. Habel, N.S. Achacoso, G.D. Friedman, M.M. Asgari
Journal: British Journal of Dermatology (2018)

Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown.
PBI-4050, a potential anti-fibrotic drug, improves liver fibrosis in Alström Syndrome, an ultra-rare disease
Authors: S. Baig, T. Geberhiwot, L. Gagnon, B. Grouix, P. Laurin, L. Foulkes, C. Dorion, F. Cesari, O. Vaughan, J. Moran
Journal: Journal of Hepatology (2018)
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Authors: Reuben L Smith, Maarten R Soeters, Rob C I Wüst, Riekelt H Houtkooper
Journal: Endocrine Reviews (2018)

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.
The evolution of treatment for HCV Genotype 3 (GT3) infected patients with advanced fibrosis/cirrhosis over time
Authors: A. Mangia, G. Cenderrello, M. Copetti, R. Santoro, F. Sogari, V. Piazzolla, N. Minerva, M. Mazzola, R. Losappio, P. Vincenzo, G. Spinzi, D. Potenza, G.D. Stefano
Journal: Journal of Hepatology (2018)