tbuckley/cabot-search huggingface dataset:
Systematic review of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for ovarian peritoneal carcinomatosis: A more efficacious way of delivering intraperitoneal chemotherapy
Authors: T. C. Chua, G. Robertson, R. Farrell, W. Liauw, T. D. Yan, D. L. Morris
Journal: Journal of Clinical Oncology (2009)

5524 Background: Advanced and recurrent ovarian cancer results in extensive dissemination of tumor within the peritoneal cavity. The current evidence suggests that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) may be a feasible option with potential benefits compared to the current standard of care in the treatment of peritoneal carcinomatosis from ovarian cancer. Methods: A systematic review of relevant studies before August 2008 was undertaken to document and report its efficacy. Each study was appraised using a predetermined protocol. The quality of studies was assessed. The patient characteristics, protocol of treatment, perioperative morbidity and mortality, and treatment outcomes were synthesized through a narrative review with full tabulation of results of all included studies. Results: In total, 15 non-randomized, observational studies were reviewed, comprising of 512 patients. All patients received HIPEC as part of the combined treatment with cytoreductive surgery. Cisplatin was the most common chemoperfusate. The mortality associated with the treatment ranged from 0 to 10%. The rates of severe morbidity ranged from 0 to 40%. The median time of follow up ranged from 14 to 64 months, the median disease-free survival ranged from 10 to 57 months and the overall median survival ranged from 22 to 64 months. In patients who had an optimal cytoreduction, the median survival ranged from 29 to 66 months, with a 3- and 5-year survival rate that ranged from 35 to 63% and 12 to 66%, respectively. Conclusions: The future for cytoreductive surgery and HIPEC in ovarian cancer is promising. More studies are called for to validate the efficacy of this treatment. For it to become generally accepted, the oncology community must commit to a randomized trial. Before this, the current treatment of cytoreductive surgery combined with adjuvant intraperitoneal and intravenous chemotherapy should remain the mainstay of treatment. No significant financial relationships to disclose.
Multiple-Drug Resistance in Human Cancer
Authors: Jeffrey S. Flier, Lisa H. Underhill, Ira Pastan, Michael Gottesman
Journal: New England Journal of Medicine (1987)

THE intensive use of chemotherapeutic agents for the treatment of cancer has resulted in the cure of many patients. Unfortunately, many cancers still do not respond to chemotherapy, and other cancers that initially do respond later become resistant. If the molecular basis of drug resistance could be understood, new types of treatment might be developed to cure these drug-resistant cancers.Drug resistance has been studied in cancer cells grown in tissue culture and selected for resistance to various therapeutic agents. With this approach, the mechanism of methotrexate resistance in cultured cells has been shown to be an increase in the . . .
Climate is not a good candidate to account for variations in aggression and violence across space and time
Authors: Hugo Mell, Lou Safra, Nicolas Baumard, Pierre O Jacquet
Journal: Behavioral and Brain Sciences (2017)

We agree with Van Lange et al. that climate is likely to affect individuals' social behavior in many ways. However, we suspect that its impact on physiology and psychology is so remote that its predictive power disintegrates almost completely through the causal chain underlying aggression and violence.
MicroRNAs in dysfunctional adipose tissue: cardiovascular implications
Authors: Basak Icli, Mark W. Feinberg
Journal: Cardiovascular Research (2017)

In this review, we focus on the emerging role of microRNAs, non-coding RNAs that regulate gene expression and signaling pathways, in dysfunctional adipose tissue. We highlight current paradigms of microRNAs involved in adipose differentiation and function in depots such as white, brown, and beige adipose tissues and potential implications of microRNA dysregulation in human disease such as obesity, inflammation, microvasculature dysfunction, and related cardiovascular diseases. We highlight accumulating studies indicating that adipocyte-derived microRNAs may not only serve as biomarkers of cardiometabolic disease, but also may directly regulate gene expression of other tissues. Finally, we discuss the future prospects, challenges, and emerging strategies for microRNA delivery and targeting for therapeutic applications in cardiovascular disease states associated with adipocyte dysfunction.
Pediatric Psoriasis Comorbidity Screening Guidelines
Authors: Emily Osier, Audrey S. Wang, Megha M. Tollefson, Kelly M. Cordoro, Stephen R. Daniels, Andrew Eichenfield, Joel M. Gelfand, Alice B. Gottlieb, Alexa B. Kimball, Mark Lebwohl, Nehal N. Mehta, Amy S. Paller, Jeffrey B. Schwimmer, Dennis M. Styne, Abby S. Van Voorhees, Wynnis L. Tom, Lawrence F. Eichenfield
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> Psoriasis is a complex inflammatory skin condition associated with serious medical comorbidities in adults, including obesity, hypertension, dyslipidemia, type 2 diabetes mellitus, psoriatic arthritis, nonalcoholic fatty liver disease, depression, anxiety, and decreased quality of life. Because psoriasis begins in childhood in almost one-third of patients, early identification of risk may be critical to minimizing effects on future health. <h3>Objective</h3> To develop the first set of guidelines for comorbidity screening for patients with pediatric psoriasis based on current evidence. <h3>Evidence Review</h3> A literature review was performed using PubMed from January 1999 through December 2015. Limiting the search to human studies published in English and removing reviews and editorials produced 153 relevant manuscripts. An expert panel in psoriasis, pediatric dermatology, pediatric rheumatology, pediatric gastroenterology, pediatric endocrinology, and adult and pediatric cardiology used the patient-centered Strength of Recommendation Taxonomy (SORT) method to evaluate and grade the quality of evidence. <h3>Findings</h3> Because of the limited number of pediatric studies published on these topics, the strength of the panel’s recommendations is classified as SORT level C expert consensus recommendations. The majority of recommendations coincide with those endorsed by the American Academy of Pediatrics for the general pediatric patient but with added attention to signs and symptoms of arthritis, depression, and anxiety. The panel also identified key areas for further investigation. <h3>Conclusions and Relevance</h3> Patients with pediatric psoriasis should receive routine screening and identification of risk factors for associated comorbidities. These guidelines are relevant for all health care providers caring for patients with pediatric psoriasis, including primary care clinicians, dermatologists, and pediatric specialists. Because these are the first pediatric guidelines, re-review and refinement will be necessary as studies further detail, and possibly stratify, risk in affected children.
HEW's Long-Term Plan for the Federal Role in Health Care
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1974)

HEW's Long-term Plan for the Federal Role in Health CareInadequacies in the provision of legal services are probably as abundant as in the provision of medical care. But since lawyers are mostly customer-financed, and write the rules that govern their trade, only a minor reform movement confronts the legal profession in this age of consumerism.Medicine, however, is an altogether different matter, for not only are broken bones more prevalent and almost always more painful than broken contracts, but the federal government calculates that last year, through Medicare, Medicaid, and other programs, it furnished 38 per cent of the . . .
A Prospective, Observational Study on the Incidence of Chemotherapy-Induced Neutropenia in Lymphoma Patients
Authors: Antonio Salar, Andrés López, Juan Pío Torres, María Dolores López, Elena Prieto, Dolores Caballero, Pilar Giraldo, Montserrat Batlle, Patricia Benedit, Teresa Garrido
Journal: Blood (2008)
Carbon tetrachloride-induced cirrhosis in rats: Influence of the acute effects of the toxin on glucose metabolism
Authors: F Mion, A Géloén, E Agosto, Y Minaire
Journal: Hepatology (1996)

In animal models, conflicting results on the effect of cirrhosis on glucose metabolism have been reported. The use of various toxins as well as differences in experimental protocols may be responsible for these controversial data. However, differences may be also be explained by the fact that glucose metabolism has been evaluated following different time intervals after cessation of the toxic injury. Therefore, we have performed intravenous glucose tolerance tests, euglycemic hyperinsulinemic clamps (at 2,6, and 30 mU/kg/min insulin infusion rates), and determination of peripheral tissue glucose metabolic index (by [3H]2-deoxy-glucose injection) in rats treated for 10 weeks with carbon tetrachloride, either 3 days (acute group) or 2 weeks (delayed group) after the last CCl4 dose was administered. Cirrhosis was confirmed by liver histological analysis, and by a 22% ( P &lt;.05) decrease in 13C-aminopyrine demethylation. In the acute group, whole-body glucose disposal was decreased at the highest insulin infusion rate only (19.7 ± 1.2 vs. 23.4 ± 1.2 mg/kg/min in controls, P &lt;.05). In contrast, results of the delayed group were not different from controls at any insulin infusion rate. Peripheral tissue glucose metabolic index was significantly decreased in all muscles tested in the acute group compared with controls. A significant decrease of glucose utilization was found in some but not all muscles in the delayed group but was less pronounced than in the acute group. In conclusion, this study showed than insulin sensitivity in cirrhotic rats is time-dependent with regard to the last CCl4 administration. These results must be taken into account when using this experimental model of liver cirrhosis.
Abstract 127: Mode of Injury Affects the Course of Regeneration and Repair in Neonatal and Adult Mouse Heart
Authors: Tal Konfino, Natalie Landa-Rouben, Jonathan Leor
Journal: Circulation Research (2013)

PURPOSE: Recent reports have demonstrated complete cardiac regeneration in newborn mice following resection of the cardiac apex. However, different types of injury could affect the mechanism of regeneration and repair. HYPOTHESIS: We aimed to test the hypothesis that the course of repair and regeneration after MI is different from apical resection in both neonatal and adult mouse heart. Methods and Results: Apical resection or permanent LAD coronary artery ligation was induced in 1-day-old or 12-week-old ICR mice. Echocardiography was used to confirm and monitor cardiac injury and remodeling. Mice were euthanized at different time points after operation, and hearts were harvested, processed, immunostained and compared with sham operated neonatal and adult hearts. Histological and immunohistochemical examination of both resected and infarcted neonatal hearts revealed inflammation and granulation tissue formation within 3 to 5 days. In the resected hearts, early regeneration was identified at the injured sites, and marked dedifferentiation of cardiomyocytes, represented by sarcomeric disassembly and marginalization, was evident around the injured areas. In addition, we noticed intensive proliferation of young cardiomyocytes which infiltrated the granulation tissue and formed a new myocardium within 21 days. In contrast, incomplete regeneration with residual small infract was detected 28 days after coronary occlusion. Echocardiography at 2,7,14 and 28 days after MI confirmed deteriorating LV function and LV remodeling with apical aneurysm formation. Surprisingly, 21 days after cardiac injury in adult mice, MI produced typical, thin, fibrotic scar whereas apical resection produced an apical tumor-like thick scar. Conclusions: The mode of injury, whether resection or infarction, affect regeneration and repair in both neonatal and adult mouse heart. Particularly, after apical resection, the newborn heart almost completely regenerates whereas regeneration is incomplete after MI, suggesting that infarction and subsequent inflammation might inhibit complete regeneration. Understanding these differences could be translated to development of new approaches to induce myocardial regeneration in adult heart.
No germline FH mutations in familial breast cancer patients
Authors: Virpi Launonen, Maija Kiuru, Rainer Lehtonen, Hannaleena Eerola, Kristiina Aittomäki, Carl Blomqvist, Heli Nevanlinna, Lauri A. Aaltonen
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1884 

Fumarate hydratase ( FH ) was recently identified as the predisposing gene for a tumor predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC) (MIM [605839][1]). In HLRCC, individuals with a germline heterozygous mutation in the FH gene typically develop benign leiomyomas of the skin and the uterus (fibroids, myomas). In a subset of the families, predisposition to renal cell carcinoma and uterine leiomyosarcoma occurs. Malignant phenotype has been detected more frequently in the mutation positive families in Finland than in other populations. Altogether three Finnish HLRCC patients carrying FH mutation in two families have been diagnosed with breast cancer. To examine whether FH could be involved in predisposition to breast cancer, we analyzed germline FH mutations from 85 Finnish breast cancer patients. Most of the cases were selected based on positive family or personal history for malignancies associated with HLRCC. No mutations were found. These results show that FH is not a major predisposing gene for familial breast cancer.

 [1]: /lookup/external-ref?link_type=OMIM&access_num=605839&atom=%2Fcanres%2F65%2F9_Supplement%2F441.3.atom
STUDIES ON HUMAN ANTIBODIES
Authors: William J. Yount, Marianne M. Dorner, Henry G. Kunkel, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1968)

The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types. Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major γG1-type. However, a high preponderance of molecules of the minor γG2-subgroup was found for antibodies to dextran, levan, and teichoic acid. These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens. Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others. The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals. Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals. Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios. The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda. The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of γG2-heavy chains and kappa light chains. By these criteria as well as others, it closely resembled myeloma proteins.
PWE-267 Urinary TLR4: a novel biomarker to identify patients with acute kidney injury in patients with acute on chronic liver failure: Abstract PWE-267 Figure 1
Authors: N Shah, F Mohammed, M Jover-Cobos, J Macnaughtan, N A Davies, R Moreau, V Paradis, K Moore, R P Mookerjee, R Jalan
Journal: Gut (2012)

<h3>Introduction</h3> Patients with stable cirrhosis often present with acute deterioration of cirrhosis secondary to precipitating illness which may progress to organ failure, a condition referred to as acute on chronic Liver failure (ACLF). A proportion of these patients develop renal dysfunction which do not fulfil criteria for the diagnosis of hepatorenal syndrome (HRS). We hypothesised that the kidneys in patients who develop renal dysfunction in ACLF would exhibit histological and biomarker evidence of acute kidney injury (AKI). Since ACLF is associated with systemic inflammatory response (SIRS) we aimed to look for Toll like receptor (TLR) 4 and 2 which recognise pathogens and when activated lead to apoptosis and production of cytokines. <h3>Methods</h3> <b>Study 1</b>: 74 subjects [healthy volunteers (6), compensated alcoholic cirrhosis (11), acute deterioration of alcoholic cirrhosis (57)] were included prospectively. Urinary biomarkers, kidney injury molecule-1 (KIM-1, a marker of renal injury), Glutathione S-Transferase (πGST, αGST; markers of proximal and distal tubular injury) (Commercial ELISA), and urinary TLR4 (Western Blotting) were measured. <b>Study 2</b>: Renal biopsies were available from 8 alcoholic cirrhosis patients (3 AKI; 5 HRS) which were stained for TLR4, TLR2 and, Caspase-3. <h3>Results</h3> <b>Study 1</b>: Nine patients developed AKI on the background of acute deterioration of cirrhosis and 3 had HRS. KIM-1, πGST and αGST were higher in patients with acute deterioration of cirrhosis compared with controls but did not differ in those with and without AKI. Urinary TLR4 values were significantly higher in patients with acute deterioration of cirrhosis with AKI (4.7±1.1) compared to controls (0.38±0.04) and stable cirrhosis (0.32±0.08) and patients with acute deterioration of cirrhosis without renal dysfunction (1.6±0.32) (p&lt;0.01) respectively. <h3>Conclusion</h3> These data provide evidence for severe tubular injury and apoptosis in patients with AKI and identifies urinary TLR4, as a novel biomarker to identify AKI in Acute deterioration of cirrhosis. <h3>Competing interests</h3> None declared.
Abstract 288: Mice With Disruptive Egfr Signaling In The Aortic Valves Develop Calcific Aortic Valve Stenosis
Authors: Bin Zhou, Bingruo Wu
Journal: Circulation Research (2013)

Calcific aortic valve stenosis is a major health problem. Despite its clinical importance, the pathogenesis of this condition remains illusive. Aortic valves are made of endothelial cells and interstitial cells, both are derived from the endocardial cells of the heart during development. We have developed a new mouse model, Nfatc1-Cre, to specifically study the biology of the valve cells during valve development. In this study, we deleted epidermal growth factor receptor (Egfr) in the aortic valves using the Nfatc1-Cre and showed by histological and biochemical analyses that this deletion caused a spectrum of pathological characteristics of human calcific aortic valve stenosis. They include increased proliferation and dedifferentiation of the valve interstitial cells, abnormal deposition of extracellular matrix, bone-like formation and calcification. The null mice eventually developed the left ventricular dysfunction, presumably secondary to the stenotic aortic valves. We also revealed by immunohistochemistry and quantitative RT-PCR the changes in gene expression involved in the epithelial-to-mesenchymal transition or osteogenic activities. Altogether, these results demonstrate that Egfr signaling in the valve endothelial and interstitial cells regulates the homeostasis of the aortic valves and suggest that patients with mutations or medications affecting the Egfr signaling may be at the risk to develop calcific aortic valve stenosis. Our study also provides the proof-of-principle data showing that the Nfatc1-Cre is a useful genetic tool to elucidate the valve-specific gene function involved in the valve homeostasis and disease.
IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection
Authors: Laura J. Pallett, Jessica Davies, Emily J. Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J.W. Easom, Alice R. Burton, Kerstin A. Stegmann, Anna Schurich, Leo Swadling, Upkar S. Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R. Davidson, Patrick T.F. Kennedy, Mala K. Maini
Journal: The Journal of Experimental Medicine (2017)

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-betloEomesloBlimp-1hiHobitlo T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69+CD103+ CXCR6+CXCR3+). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance.
A new HDV mouse model identifies mitochondrial antiviral signaling protein (MAVS) as a key player in IFN-β induction
Authors: Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
Journal: Journal of Hepatology (2017)