tbuckley/cabot-search huggingface dataset:
Tumor Neurobiology and the War of Nerves in Cancer
Authors: Sam Faulkner, Phillip Jobling, Brayden March, Chen Chen Jiang, Hubert Hondermarck
Journal: Cancer Discovery (2019)

Nerves are emerging regulators of cancer progression. Cancer cells induce the outgrowth of nerves in the tumor microenvironment through the release of neurotrophic factors, and in return nerves liberate neurotransmitters that activate cancer growth and dissemination. Although sympathetic nerves drive tumor angiogenesis via the liberation of noradrenaline, sensory and parasympathetic nerves stimulate cancer stem cells. Interestingly, recent evidence indicates that parasympathetic nerves can eventually inhibit tumor progression, suggesting a yin-yang type of regulation of cancer by nerves. From a broader perspective, the question of a higher level of control of cancer development by the central nervous system should be raised. SIGNIFICANCE: Nerves are emerging regulators of cancer initiation, progression, and metastasis. Here, we review the evidence to date and explore the basic and clinical ramifications of these findings.
Quality and Safety in Healthcare, Part LII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

The study of positive psychology has brought to light multiple ways to improve one's ability to bounce back from setbacks and deal better with stress. The individual should focus on his/her accomplishments, not dwell on mistakes, work to improve relationships with others, find meaning in work, and spend the time required to have happiness. Being able to recognize when situations are too stressful and understand the need to take breaks from them, especially by acquiring new knowledge, is important and effective. It is often quite helpful to utilize coaching based on positive psychology to improve one's resiliency and recover from burnout.
Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303
Authors: Nancy L. Bartlett, Wyndham H. Wilson, Sin-Ho Jung, Eric D. Hsi, Matthew J. Maurer, Levi D. Pederson, Mei-Yin C. Polley, Brandelyn N. Pitcher, Bruce D. Cheson, Brad S. Kahl, Jonathan W. Friedberg, Louis M. Staudt, Nina D. Wagner-Johnston, Kristie A. Blum, Jeremy S. Abramson, Nishitha M. Reddy, Jane N. Winter, Julie E. Chang, Ajay K. Gopal, Amy Chadburn, Susan Mathew, Richard I. Fisher, Kristy L. Richards, Heiko Schöder, Andrew D. Zelenetz, John P. Leonard
Journal: Journal of Clinical Oncology (2019)

Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
Assessment of Crohn’s disease-associated small bowel strictures and fibrosis on cross-sectional imaging: a systematic review
Authors: Dominik Bettenworth, Arne Bokemeyer, Mark Baker, Ren Mao, Claire E Parker, Tran Nguyen, Christopher Ma, Julián Panés, Jordi Rimola, Joel G Fletcher, Vipul Jairath, Brian G Feagan, Florian Rieder
Journal: Gut (2019)

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.
Author Correction: Liver macrophages regulate systemic metabolism through non-inflammatory factors
Authors: Cecilia Morgantini, Jennifer Jager, Xidan Li, Laura Levi, Valerio Azzimato, André Sulen, Emelie Barreby, Connie Xu, Michaela Tencerova, Erik Näslund, Chanchal Kumar, Francisco Verdeguer, Sara Straniero, Kjell Hultenby, Niklas K. Björkström, Ewa Ellis, Mikael Rydén, Claudia Kutter, Tracey Hurrell, Volker M. Lauschke, Jeremie Boucher, Aleš Tomčala, Gabriela Krejčová, Adam Bajgar, Myriam Aouadi
Journal: Nature Metabolism (2021)
The Liver–α-Cell Axis and Type 2 Diabetes
Authors: Nicolai J Wewer Albrechtsen, Jens Pedersen, Katrine D Galsgaard, Marie Winther-Sørensen, Malte P Suppli, Lina Janah, Jesper Gromada, Hendrik Vilstrup, Filip K Knop, Jens J Holst
Journal: Endocrine Reviews (2019)

Abstract Both type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index, and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist administration. Emerging data now indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D. Thus, fatty liver disease, most often secondary to overeating, may result in impaired amino acid turnover, leading to increased plasma concentrations of certain glucagonotropic amino acids (e.g., alanine). This, in turn, causes increased glucagon secretion that may help to restore amino acid turnover and ureagenesis, but it may eventually also lead to increased hepatic glucose production, a hallmark of T2D. Early experimental findings support the hypothesis that hepatic steatosis impairs glucagon’s actions on amino acid turnover and ureagenesis. Hepatic steatosis also impairs hepatic insulin sensitivity and clearance that, together with hyperglycemia and hyperaminoacidemia, lead to peripheral hyperinsulinemia; systemic hyperinsulinemia may itself contribute to worsen peripheral insulin resistance. Additionally, obesity is accompanied by an impaired incretin effect, causing meal-related glucose intolerance. Lipid-induced impairment of hepatic sensitivity, not only to insulin but potentially also to glucagon, resulting in both hyperinsulinemia and hyperglucagonemia, may therefore contribute to the development of T2D at least in a subset of individuals with NAFLD.
Efficacy and Safety of Ponatinib in Chronic Phase-Chronic Myeloid Leukemia (CP-CML) According to the Extent of Treatment with Prior Tyrosine Kinase Inhibitors (TKIs): Final (5-Year) Results of the PACE Study
Authors: Andreas Hochhaus, Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D. le Coutre, Ronald Paquette, Charles Chuah, Franck Emmanuel Nicolini, Moshe Talpaz, Daniel J. DeAngelo, Elisabetta Abruzzese, Delphine Rea, Martin C. Mueller, Carlo Gambacorti-Passerini, Fausto Castagnetti, Dragana Milojkovic, Stephanie Lustgarten, Victor M. Rivera, Frank Neumann, Francois Guilhot, Michael W. Deininger, Timothy P. Hughes, Neil P. Shah, Hagop M. Kantarjian
Journal: Blood (2017)
Increased Odds of Survival or Prevention of Severe Neurological Injury in Extremely Low-Gestational-Age Neonates
Authors: Ryan M. McAdams
Journal: JAMA Network Open (2019)

Abhay Lodha, MD, DM, MSc; Prakesh S. Shah, MD, MSc; Amuchou Singh Soraisham, DM, MSc; Yacov Rabi, MD; Ayman Abou Mehrem, MD, MSc; Nalini Singhal, MD; for the Canadian Neonatal Network Investigators
A public health approach to alcohol use and its related harms in Iran
Authors: Mostafa Shokoohi, Afarin Rahimi-Movaghar, Alireza Noroozi, Mohammad Karamouzian
Journal: The Lancet Public Health (2019)

In Iran, alcohol consumption, production, and trade are criminalised for Muslim citizens (ie, about 99% of the population);1 however, bootleg alcohol is common and alcohol consumption is associated with a number of harms (eg, violence, injuries).2,3 A nation-wide household mental health survey suggested that 5·7% of the adult population had consumed alcohol in the previous year,3 with a higher prevalence among men, young adults, single adults, urban areas, and some geographical regions.3,4 Moreover, alcohol poisoning outbreaks due to the consumption of substandard alcoholic drinks are frequent and contribute to alcohol poisoning deaths and hospitalisations across the country.
In patients with idiopathic pulmonary fibrosis the presence of hiatus hernia is associated with disease progression and mortality
Authors: John A. Mackintosh, Sujal R. Desai, Huzaifa Adamali, Kinesh Patel, Felix Chua, Anand Devaraj, Vasilis Kouranos, Maria Kokosi, George Margaritopoulos, Elisabetta A. Renzoni, Athol U. Wells, Philip L. Molyneaux, Sacheen Kumar, Toby M. Maher, Peter M. George
Journal: European Respiratory Journal (2019)

<b>For IPF patients, the presence of hiatus hernia is associated with lung function decline and increased mortality. This observation supports the view that hiatus hernia may influence pathogenic mechanisms involved in IPF disease progression.</b>http://ow.ly/hPAY30omE9o
Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes
Authors: Jérôme Hadjadj, Nathalie Aladjidi, Helder Fernandes, Guy Leverger, Aude Magérus-Chatinet, Fabienne Mazerolles, Marie-Claude Stolzenberg, Sidonie Jacques, Capucine Picard, Jérémie Rosain, Cécile Fourrage, Sylvain Hanein, Mohammed Zarhrate, Marlène Pasquet, Wadih Abou Chahla, Vincent Barlogis, Yves Bertrand, Isabelle Pellier, Elodie Colomb Bottollier, Fanny Fouyssac, Pascale Blouin, Caroline Thomas, Nathalie Cheikh, Eric Dore, Corinne Pondarre, Dominique Plantaz, Eric Jeziorski, Frédéric Millot, Nicolas Garcelon, Stéphane Ducassou, Yves Perel, Thierry Leblanc, Bénédicte Neven, Alain Fischer, Frédéric Rieux-Laucat
Journal: Blood (2019)
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation
Authors: Freya R. Svedberg, Sheila L. Brown, Maria Z. Krauss, Laura Campbell, Catherine Sharpe, Maryam Clausen, Gareth J. Howell, Howard Clark, Jens Madsen, Christopher M. Evans, Tara E. Sutherland, Alasdair C. Ivens, David J. Thornton, Richard K. Grencis, Tracy Hussell, Danen M. Cunoosamy, Peter C. Cook, Andrew S. MacDonald
Journal: Nature Immunology (2019)
Endoscopic management of gastrocolic fistula after endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ)
Authors: Khanh Do-Cong Pham, Roald Flesland Havre
Journal: Endoscopy (2019)

Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) with a lumen-apposing metal stent (LAMS) is a technique used to create a fistula between the stomach and the jejunum with the aim of relieving the symptoms of gastric outlet obstruction (GOO) [1] [2]. One of the most feared complications is accidental deployment of the stent into the colon. We describe a patient who developed a delayed gastrocolostomy after EUS-GJ, which was managed endoscopically.
Letter to the Editor: Proton Pump Inhibitors in Cirrhosis: A Marker of Morbid Conditions or a Cause of Mortality?
Authors: Andrew M. Moon, Paul H. Hayashi, A. Sidney Barritt
Journal: Hepatology (2019)

Supported in part by the National Institutes of Health (T32 DK007634). Potential conflict of interest: Dr. Barritt consults for Target PharmaSolutions and Dova Pharmaceuticals. To the Editor: We read with interest the study by Nardelli et al., which adds to a growing literature on the potential ills of proton pump inhibitors (PPIs) in patients with cirrhosis.1 Their prospective design allowed for assessment of minimal hepatic encephalopathy (HE), and they reported that PPI use was independently associated with minimal HE, overt HE, and mortality. While we applaud the authors’ efforts, we are concerned about residual confounding that may have led to misinterpretation of mortality results. The authors outline that decreased gastric acid provides biological plausibility for the association between PPIs and Clostridium difficile colitis, spontaneous bacterial peritonitis, and pneumonia, which could explain some increased mortality in PPI users.2 However, infections accounted for just over one third of deaths overall, type of infection was unreported, and cause of death stratified by PPI use was not included. PPI use was weakly associated with overt HE, but this is unlikely to account for the reported mortality, even when considered in combination with infections. This begs the question of whether other explanations may exonerate PPIs. It is possible that PPI use may merely be a marker of patient comorbidities. Increased health care use, smoking, obesity, nonsteroidal anti‐inflammatory drug use, and vascular disease are all potential confounders of PPI use and death.3 These factors were not assessed. Furthermore, 42% of PPI users had “an appropriate” indication, which included recent gastrointestinal bleed and/or endoscopic ligation of varices, both of which may increase mortality independent of Model for End‐Stage Liver Disease or Child‐Pugh score. It would therefore be worthwhile to examine the mortality among PPI users with strong versus weak indications. Despite these limitations, this study provides a valuable addition to the literature on PPIs and HE and provides important data arguing for the judicious discontinuance of PPIs in patients with cirrhosis. However, we have a difficult time accepting PPIs as an independent risk factor for all of the deaths observed without knowing more about the causes of death and the comorbidities that come with PPI use.
Abstract 264: Inhibiting Fibronectin Improves Cardiac Function in a Mouse Model of Heart Failure
Authors: Iñigo Valiente-Alandi, Michelle Nieman, Burns C. Blaxall
Journal: Circulation Research (2016)

Heart failure (HF) is a devastating disease with poor prognosis. Hallmarks of HF include pathological fibrosis, remodeling and reduced function. In response to cardiac injury, cardiac fibroblasts (CF) undergo pathologic transition to a myofibroblast (MF) phenotype, characterized by excess production of collagen and other myocardial extracellular matrix (ECM) components, thus exacerbating HF. The ECM protein fibronectin (FN) plays an essential role in pathologic remodeling of the ECM in HF. FN polymerization tightly regulates the assembly of collagens and promotes cell proliferation, growth, migration and contractility. We hypothesize that inhibiting FN polymerization utilizing novel peptides will attenuate cardiac remodeling by limiting CF activation and fibrosis. To investigate this hypothesis, we administered daily injections of the FN polymerization inhibitory peptide pUR4 into wild type animals after ischemia-reperfusion (IR) injury for 1 week, and hearts were harvested 4 weeks post-IR. Mice receiving pUR4 demonstrated significant improvement in cardiac function compared to control peptide-treated animals. In addition, pUR4-treated animals showed a robust reduction of fibrosis, inflammatory cell infiltration, pro-inflammatory cytokines, apoptosis and hypertrophy. The information gleaned from the in vitro data obtained from isolated CF, from unchallenged or injured hearts, treated with pUR4 or control peptide suggested attenuation in cell migration and proliferation cell functions. To examine the impact of FN genetic ablation in cardiac function and cardiac fibrosis, we investigated the fibroblast-mediated role of FN in pathologic cardiac remodeling utilizing our fibroblast-restricted Periostin mERCremER ;FN Flox/Flox (Periostin FN-KO). Analysis of cardiac function by echocardiography of Periostin-FN-KO 4 weeks post-IR revealed limited cardioprotective effect compare to the control group (FN Flox/Flox ). This data suggest that inhibiting FN polymerization may be cardioprotective following cardiac injury, attenuating the pathological effects of FN overproduction and polymerization in the activated CF after injury. Limiting FN polymerization will possible lead to the generation of novel treatments for HF.
Cross-reactive public TCR sequences undergo positive selection in the human thymic repertoire
Authors: Mohsen Khosravi-Maharlooei, Aleksandar Obradovic, Aditya Misra, Keshav Motwani, Markus Holzl, Howard R. Seay, Susan DeWolf, Grace Nauman, Nichole Danzl, Haowei Li, Siu-hong Ho, Robert Winchester, Yufeng Shen, Todd M. Brusko, Megan Sykes
Journal: Journal of Clinical Investigation (2019)

We investigated human T-cell repertoire formation using high throughput TCRβ CDR3 sequencing in immunodeficient mice receiving human hematopoietic stem cells (HSCs) and human thymus grafts. Replicate humanized mice generated diverse and highly divergent repertoires. Repertoire narrowing and increased CDR3β sharing was observed during thymocyte selection. While hydrophobicity analysis implicated self-peptides in positive selection of the overall repertoire, positive selection favored shorter shared sequences that had reduced hydrophobicity at positions 6 and 7 of CDR3βs, suggesting weaker interactions with self-peptides than unshared sequences, possibly allowing escape from negative selection. Sharing was similar between autologous and allogeneic thymi and occurred between different cell subsets. Shared sequences were enriched for allo-crossreactive CDR3βs and for Type 1 diabetes-associated autoreactive CDR3βs. Single-cell TCR-sequencing showed increased sharing of CDR3αs compared to CDR3βs between mice. Our data collectively implicate preferential positive selection for shared human CDR3βs that are highly cross-reactive. While previous studies suggested a role for recombination bias in producing "public" sequences in mice, our study is the first to demonstrate a role for thymic selection. Our results implicate positive selection for promiscuous TCRβ sequences that likely evade negative selection, due to their low affinity for self-ligands, in the abundance of "public" human TCRβ sequences.
Temozolomide Treatment Induces lncRNA MALAT1 in an NF-κB and p53 Codependent Manner in Glioblastoma
Authors: David J. Voce, Giovanna M. Bernal, Longtao Wu, Clayton D. Crawley, Wei Zhang, Nassir M. Mansour, Kirk E. Cahill, Szymon J. Szymura, Abhineet Uppal, David R. Raleigh, Ruben Spretz, Luis Nunez, Gustavo Larsen, Nikolai N. Khodarev, Ralph R. Weichselbaum, Bakhtiar Yamini
Journal: Cancer Research (2019)

Alkylating chemotherapy is a central component of the management of glioblastoma (GBM). Among the factors that regulate the response to alkylation damage, NF-κB acts to both promote and block cytotoxicity. In this study, we used genome-wide expression analysis in U87 GBM to identify NF-κB-dependent factors altered in response to temozolomide and found the long noncoding RNA (lncRNA) MALAT1 as one of the most significantly upregulated. In addition, we demonstrated that MALAT1 expression was coregulated by p50 (p105) and p53 via novel κB- and p53-binding sites in the proximal MALAT1 coding region. Temozolomide treatment inhibited p50 recruitment to its cognate element as a function of Ser329 phosphorylation while concomitantly increasing p53 recruitment. Moreover, luciferase reporter studies demonstrated that both κB and p53 cis-elements were required for efficient transactivation in response to temozolomide. Depletion of MALAT1 sensitized patient-derived GBM cells to temozolomide cytotoxicity, and in vivo delivery of nanoparticle-encapsulated anti-MALAT1 siRNA increased the efficacy of temozolomide in mice bearing intracranial GBM xenografts. Despite these observations, in situ hybridization of GBM specimens and analysis of publicly available datasets revealed that MALAT1 expression within GBM tissue was not prognostic of overall survival. Together, these findings support MALAT1 as a target for chemosensitization of GBM and identify p50 and p52 as primary regulators of this ncRNA. SIGNIFICANCE: These findings identify NF-κB and p53 as regulators of the lncRNA MALAT1 and suggest MALAT1 as a potential target for the chemosensitization of GBM.
The “Fibrous Nest”: A Biotope including WNT Signals, Extracellular Matrix Remodeling and Stemness in Hepatocellular Carcinoma
Authors: R. Désert, S. Mebarki, M. Desille, M. Sicard, E. Lavergne, S. Renaud, D. Bergeat, L. Sulpice, C. Perret, B. Turlin, B. Clément, O. Musso
Journal: Journal of Hepatology (2016)
Closed-Loop Ventilation (intellivent-Asv®) Based On End-Tidal Co2 Signal Can Be Used To Control Capnia In Neuro Critical Care: Preliminary Results Of A Prospective Interventional Study.
Authors: P. Jolliet, A. Polupan, L. Piquilloud, I. Matskovskiy, A. Oshorov, D. Novotni, T. Laubscher, M. Oddo, J-P. Revelly
Journal: American Journal of Respiratory and Critical Care Medicine (2015)