tbuckley/cabot-search huggingface dataset:
Expectation and Patient Preference – does it Matter?<sup>1</sup>
Authors: H Berry, Brenda Bloom, B E W Mace, E B D Hamilton, L Fernandes, M Molloy, I A Williams
Journal: Journal of the Royal Society of Medicine (1980)

Admission to clinical trials is often based on the assumption of homogeneity of the population. A group of 60 patients, all with pain in the neck or shoulder of at least 3 months duration, were studied. Expectation was graded before treatments were started by sharing out 100 points between freedom from side effects, pain relief, depression relief, improved mobility, improved sleep and speed of action. A double-blind crossover study of two established anti-inflammatory analgesics and placebo was carried out. Using analogue scales, patients were asked to grade their response. Side effects were recorded, and preference was established at the end of the study.Although all the patients were in sufficient pain to require medical attention, some rated relief of depression, improvement in sleep or lack of side effects as more important than pain relief. Differences between drug and placebo were most clearly demonstrated in those patients whose main concern was improved mobility. In our view it is important to select patients who are in need of a dominant property of a drug for a trial of this property and this may have ramifications across the medical spectrum.
ISOLATION AND RECONSTITUTION OF NEURONAL ION TRANSPORT PROTEINS
Authors: S. M. Goldin, E. G. Moczydlowski, D. M. Papazian
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants
Authors: Karen Milcent, Sabine Faesch, Christèle Gras-Le Guen, François Dubos, Claire Poulalhon, Isabelle Badier, Elisabeth Marc, Christine Laguille, Loïc de Pontual, Alexis Mosca, Gisèle Nissack, Sandra Biscardi, Hélène Le Hors, Ferielle Louillet, Andreea Madalina Dumitrescu, Philippe Babe, Christelle Vauloup-Fellous, Jean Bouyer, Vincent Gajdos
Journal: JAMA Pediatrics (2015)

The procalcitonin (PCT) assay is an accurate screening test for identifying invasive bacterial infection (IBI); however, data on the PCT assay in very young infants are insufficient.To assess the diagnostic characteristics of the PCT assay for detecting serious bacterial infection (SBI) and IBI in febrile infants aged 7 to 91 days.A prospective cohort study that included infants aged 7 to 91 days admitted for fever to 15 French pediatric emergency departments was conducted for a period of 30 months (October 1, 2008, through March 31, 2011). The data management and analysis were performed from October 1, 2011, through October 31, 2014.The diagnostic characteristics of the PCT assay, C-reactive protein (CRP) concentration, white blood cell (WBC) count, and absolute neutrophil cell (ANC) count for detecting SBI and IBI were described and compared for the overall population and subgroups of infants according to the age and the duration of fever. Laboratory test cutoff values were calculated based on receiver operating characteristic (ROC) curve analysis. The SBIs were defined as a pathogenic bacteria in positive culture of blood, cerebrospinal fluid, urine, or stool samples, including bacteremia and bacterial meningitis classified as IBIs.Among the 2047 infants included, 139 (6.8%) were diagnosed as having an SBI and 21 (1.0%) as having an IBI (11.0% and 1.7% of those with blood culture (n = 1258), respectively). The PCT assay offered an area under the curve (AUC) of ROC curve similar to that for CRP concentration for the detection of SBI (AUC, 0.81; 95% CI, 0.75-0.86; vs AUC, 0.80; 95% CI, 0.75-0.85; P = .70). The AUC ROC curve for the detection of IBI for the PCT assay was significantly higher than that for the CRP concentration (AUC, 0.91; 95% CI, 0.83-0.99; vs AUC, 0.77; 95% CI, 0.65-0.89; P = .002). Using a cutoff value of 0.3 ng/mL for PCT and 20 mg/L for CRP, negative likelihood ratios were 0.3 (95% CI, 0.2-0.5) for identifying SBI and 0.1 (95% CI, 0.03-0.4) and 0.3 (95% CI, 0.2-0.7) for identifying IBI, respectively. Similar results were obtained for the subgroup of infants younger than 1 month and for those with fever lasting less than 6 hours.The PCT assay has better diagnostic accuracy than CRP measurement for detecting IBI; the 2 tests perform similarly for identifying SBI in febrile infants aged 7 to 91 days.
Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment
Authors: Chen-Chun Lin, Chien-Fu Hung, Wei-Ting Chen, Shi-Ming Lin
Journal: Liver Cancer (2015)

&lt;b&gt;&lt;i&gt;Aim: &lt;/i&gt;&lt;/b&gt;The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p&lt;0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p&lt;0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p&lt;0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS.
The Reorganization of Somatosensory Cortex Following Peripheral Nerve Damage in Adult and Developing Mammals
Authors: J H Kaas, M M Merzenich, H P Killackey
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement
Authors: Nick Webborn, Alun Williams, Mike McNamee, Claude Bouchard, Yannis Pitsiladis, Ildus Ahmetov, Euan Ashley, Nuala Byrne, Silvia Camporesi, Malcolm Collins, Paul Dijkstra, Nir Eynon, Noriyuki Fuku, Fleur C Garton, Nils Hoppe, Søren Holm, Jane Kaye, Vassilis Klissouras, Alejandro Lucia, Kamiel Maase, Colin Moran, Kathryn N North, Fabio Pigozzi, Guan Wang
Journal: British Journal of Sports Medicine (2015)

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future.
Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells
Authors: Eveline M. Delemarre, Theo van den Broek, Gerdien Mijnheer, Jenny Meerding, Ellen J. Wehrens, Sven Olek, Marianne Boes, Martijn J. C. van Herwijnen, Femke Broere, Annet van Royen, Nico M. Wulffraat, Berent J. Prakken, Eric Spierings, Femke van Wijk
Journal: Blood (2015)
Herpes zoster in patients with bullous pemphigoid: a population-based case-control and cohort study
Authors: B.J. Barrick, J.D. Barrick, C.H. Weaver, C.M. Lohse, C.N. Wieland, A.N. Kalaaji, J.S. Lehman
Journal: British Journal of Dermatology (2015)

Herpes zoster in patients with bullous pemphigoid: A population-based case-control and cohort study Benjamin Barrick, DO, Mayo Clinic, Rochester, MN, United States; Joshua Barrick, Kansas City University of Medicine and Biosciences, Kansas City, MO, United States; Chad Weaver, MD, Mayo Clinic, Rochester, MN, United States; Christine Lohse, MS, Mayo Clinic, Rochester, MN, United States; Carilyn Wieland, MD, Mayo Clinic, Rochester, MN, United States; Amer Kalaaji, MD, Mayo Clinic, Rochester, MN, United States; Julia Lehman, MD, Mayo Clinic, Rochester, MN, United States
A modified p53 adenoviral vector is more potent than wild-type p53 in bladder cancer cells
Authors: William F. Benedict, Xin-Qiao Zhang, Wei Zhang
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4596 

Because some bladder cancer cells are resistant to the introduction of wild-type p53, one potential way to improve cancer gene therapy to this tumor type may be to modify the wild-type p53 gene. Our previous study has demonstrated Asp substitution at Thr18 and Ser 20 within an α-helical segment of the transactivation domain can markedly reduce Mdm-2 interaction, upregulate transactivation of cell-cycle and apoptotic regulatory targets, and decrease cellular proliferation (Jabbar and Zhang, Cancer Biol.& Ther.,1:277-283, 2002). We therefore generated an adenoviral vector (Ad-p53-P) in which T18 and S20 were substituted by aspartic acid. We then compared the cytotoxity and growth suppression of wild- type and modified p53 by both MTT and trypan-blue exclusion studies. We found the adenoviral vector expressing the modified p53 (50-100 MO1) significantly inhibits the cell growth and is cytotoxic to UC11 (wild type p53) and UC14 (mutated p53) cells compared to an adenoviral vector expressing wild-type p53 at the same MOIs (p=<0.001). It was equally cytotoxic in the UC3 cell line which has a deletion in p53 and expresses no p53. This modified p53 construct may therefore provide an improvement over wild-type p53 for the treatment of bladder cancer using various gene therapy strategies.
Variation in ECT use in the United States
Authors: R C Hermann, R A Dorwart, C W Hoover, J Brody
Journal: American Journal of Psychiatry (1995)

The authors measured the variation in ECT utilization rates across 317 metropolitan statistical areas of the United States and determined to what degree this variation is associated with health care system characteristics, demographic factors, and the stringency of state regulation of ECT.Data from APA's 1988-1989 Professional Activities Survey were used to estimate ECT utilization rates for the metropolitan statistical areas. Multiple regression analysis was used to determine the relative influence of provider, demographic, and regulatory factors on variation in ECT use across areas.Among the psychiatrists surveyed, 17,729 reported treating 4,398 patients with ECT during the study period. No ECT use was reported in 115 metropolitan statistical areas. Among the remaining 202 metropolitan statistical areas, annual ECT use varied from 0.4 to 81.2 patients per 10,000 population. The strongest predictors of variation in ECT use across metropolitan statistical areas were the number of psychiatrists, number of primary care physicians, number of private hospital beds per capita, and stringency of state regulation of ECT.Rates of ECT use were highly variable, higher than for most medical and surgical procedures. In some urban areas, access to ECT appears limited. Predictors of variation in ECT rates have implications for expanding access to the procedure. The extent of variation suggests psychiatrists continue to lack consensus regarding the use of ECT. Better data on the effectiveness of psychiatric treatments may lead to a broader professional consensus and may narrow variations in clinical practices.
Development of a multicentre randomised controlled trial of screening and brief alcohol intervention to prevent risky drinking in young people in a high-school setting (SIPS JR-HIGH)
Authors: Emma Louise Giles, Stephanie Scott, Simon Coulton, Paolo Deluca, Colin Drummond, Erin Graybill, Denise Howel, Eileen Kaner, Elaine McColl, Ruth McGovern, Elaine Stamp, Harry Sumnall, Les Tate, Liz Todd, Dorothy Newbury-Birch
Journal: The Lancet (2015)
Abstract 3961: Utility of mir-21 detection by rapid chromogenic <i>in-situ</i> hybridization in the diagnosis of well and moderately differentiated hepatocellular carcinoma
Authors: Ravindra Kolhe, Amyn Rojiani, Ashis Mondal, Abhishek A. Mangaonkar
Journal: Cancer Research (2015)

Abstract Background: An estimated 80-90% of all hepatocellular carcinomas (HCC) arise from cirrhotic liver in chronic hepatitis B or C infection. Identifying well-differentiated HCC arising in the background of cirrhosis is a challenging task relying solely on morphology of core biopsies. In addition, presence of dysplasia (micro/macro) in cirrhotic nodules makes the task more difficult. In HCC, microRNAs (miRNAs) have an aberrant expression profile with possible applications in diagnosis, especially for early, symptomatic disease. Sub-cellular and tissue localization of miRNAs may help us understand their biological roles and contribution to disease along with aiding diagnosis. Design: The aim of this study was to evaluate the utility of mir-21 detection by rapid chromogenic in-situ hybridization (CISH) as a diagnostic tool in the setting of well and moderately differentiated HCCs. Archival blocks and slides were retrieved and reviewed after obtaining IRB approval (table 1). Manufacturers guidelines were followed for CISH (NAR-1, FAM-labeled Has-miR-21 probe) on a total of 202 cases. Nuclear mir-21 CISH stain was graded as: negative (-), weak (1+), moderate (2+) or strong (3+) and distribution was graded as: focal (&amp;lt;10%), multifocal (10-50%) or diffuse (&amp;gt;50%). Table 1.Table showing cases considered for mir-21 detection by CISH.HistologyNumber of casesHCC150Intrahepatic cholangiocarcinoma12Metastases from colonic adenocarcinoma23Metastases from gallbladder adenocarcinoma5Normal liver tissue12 Results: Neoplastic cells in HCC showed a strong (2-3) multifocal to diffuse nuclear staining for mir-21 in 100% of the cases of whole tissue slides and 91% of HCC cases in tissue microarray slides when compared to the staining pattern seen in normal liver cells (0%). As expected, 85% of cases with liver metastases from colonic and gallbladder adenocarcinoma showed strong nuclear staining for mir-21. Conclusion: Rapid CISH technique can clearly identify increased nuclear expression of mir-21 and aid in diagnosis of well and moderately differentiated HCC. Citation Format: Ravindra Kolhe, Amyn Rojiani, Ashis Mondal, Abhishek A. Mangaonkar. Utility of mir-21 detection by rapid chromogenic in-situ hybridization in the diagnosis of well and moderately differentiated hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3961. doi:10.1158/1538-7445.AM2015-3961
Pericarditis and Renal Failure
Authors: R Renfrew, T J Buselmeier, C M Kjellstrand
Journal: Annual Review of Medicine (1980)

The spectrum of pericardial disease in association with uremia has broad­ ened with the therapeutic advances for end-stage renal failure. The pericar­ ditis that Bright initially described in 1836 (1) is most certainly a different entity etiologically, pathologically, and therapeutically from the pericarditis that occurs in well-dialyzed patients of today. Pericarditis associated with end-stage renal disease can be categorized into uremic, dialysis, and constrictive pericarditis (Table 1) (2). Uremic pericarditis occurs in patients with severe end-stage azotemia and uremia who have not previously received dialysis therapy. If the uremia is not treated, this form of pericarditis indicates a very poor prognosis. If the underlying uremia is corrected, the pericarditis will also respond to therapy. Dialysis pericarditis occurs in two groups of patients who have already been stabilized on chronic hemodialysis. The first are patients who have a subclinical effusion detected by echocardiography, and second are patients who have clinically detectable pericarditis or pericardial effusion. These latter patients may or may not have a preceding exacerbating factor. Constrictive pericarditis usually has a subacute or chronic progress, and therapeutic implications differ from the other two forms of pericardial disease. Many authors describing the incidence, symptoms, results, and complica­ tions of therapy have not clearly distinguished between the groups of peri­ carditis as classified in Table 1. This probably accounts for wide variation in incidence or frequency figures. If one bases the incidence of pericarditis on routine screening of asymptomatic patients with echocardiography, the result is higher than when the incidence is based on severe clinical symp-
Efficacy and Safety of Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes
Authors: Robert R. Henry, Payal Thakkar, Cindy Tong, David Polidori, Maria Alba
Journal: Diabetes Care (2015)

OBJECTIVE This study assessed the efficacy and safety of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, as add-on to insulin in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This 18-week, double-blind, phase 2 study randomized 351 patients (HbA1c 7.0–9.0% [53–75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion to canagliflozin 100 or 300 mg or placebo. The primary end point was the proportion of patients achieving at week 18 both HbA1c reduction from baseline of ≥0.4% (≥4.4 mmol/mol) and no increase in body weight. Other end points included changes in HbA1c, body weight, and insulin dose, as well as hypoglycemia incidence. Safety was assessed by adverse event (AE) reports. RESULTS More patients had both HbA1c reduction ≥0.4% and no increase in body weight with canagliflozin 100 and 300 mg versus placebo at week 18 (36.9%, 41.4%, 14.5%, respectively; P &amp;lt; 0.001). Both canagliflozin doses provided reductions in HbA1c, body weight, and insulin dose versus placebo over 18 weeks. The incidence of hypoglycemia was similar across groups; severe hypoglycemia rates were low (1.7–6.8%). Overall incidence of AEs was 55.6%, 67.5%, and 54.7% with canagliflozin 100 and 300 mg and placebo; discontinuation rates were low (0.9–1.3%). Increased incidence of ketone-related AEs (5.1%, 9.4%, 0%), including the specific AE of diabetic ketoacidosis (DKA) (4.3%, 6.0%, 0%), was seen with canagliflozin 100 and 300 mg versus placebo. CONCLUSIONS Canagliflozin provided reductions in HbA1c, body weight, and insulin dose with no increase in hypoglycemia, but increased rates of ketone-related AEs, including DKA, in adults with type 1 diabetes inadequately controlled with insulin.
Long-Term Balancing Selection in LAD1 Maintains a Missense Trans-Species Polymorphism in Humans, Chimpanzees, and Bonobos
Authors: João C. Teixeira, Cesare de Filippo, Antje Weihmann, Juan R. Meneu, Fernando Racimo, Michael Dannemann, Birgit Nickel, Anne Fischer, Michel Halbwax, Claudine Andre, Rebeca Atencia, Matthias Meyer, Genís Parra, Svante Pääbo, Aida M. Andrés
Journal: Molecular Biology and Evolution (2015)

Balancing selection maintains advantageous genetic and phenotypic diversity in populations. When selection acts for long evolutionary periods selected polymorphisms may survive species splits and segregate in present-day populations of different species. Here, we investigate the role of long-term balancing selection in the evolution of protein-coding sequences in the Homo-Pan clade. We sequenced the exome of 20 humans, 20 chimpanzees, and 20 bonobos and detected eight coding trans-species polymorphisms (trSNPs) that are shared among the three species and have segregated for approximately 14 My of independent evolution. Although the majority of these trSNPs were found in three genes of the major histocompatibility locus cluster, we also uncovered one coding trSNP (rs12088790) in the gene LAD1. All these trSNPs show clustering of sequences by allele rather than by species and also exhibit other signatures of long-term balancing selection, such as segregating at intermediate frequency and lying in a locus with high genetic diversity. Here, we focus on the trSNP in LAD1, a gene that encodes for Ladinin-1, a collagenous anchoring filament protein of basement membrane that is responsible for maintaining cohesion at the dermal-epidermal junction; the gene is also an autoantigen responsible for linear IgA disease. This trSNP results in a missense change (Leucine257Proline) and, besides altering the protein sequence, is associated with changes in gene expression of LAD1.
Prognostic value of promoter hypermethylation of tumor suppressor genes in malignant pleural fluid
Authors: Maribel Botana-Rial, Loreta de Chiara, Virginia Leiro-Fernández, Diana Valverde, Cristina Represas Represas, Ana Isabel González-Silva, Alberto Fernández-Villar
Journal: European Respiratory Journal (2011)

Background: To determine the prognostic value of promoter hypermethylation of p16/INK4a, MGMT, BRCA1 and RAR β genes in pleural fluid (PF) and other clinicopathological parameters in malignant pleural effusion (MPE).  Methods: We evaluated 49 patients.We recorded clinical characteristics, characteristics of the PF, the detection of promotor hypermethylation of the tumor suppressor genes in PF by methylation-specific polymerase chain reaction.  Results: We inclued 37 (75.5%) lung cancer patients and 12 (24.6%) with others epithelial neoplasias.The median time of global survival was of 255.5 (IC 95%:56-488.5) days.Parameters associated with a minor survival were: the presence of others metastasis (p=0.003); no chemotherapy treatment (p=0.001); pH  Conclusions: In patients with lung adenocarcinoma, the presence of promotor hypermethilation of genes and history of chemotherapy treatment were significantly associated with major survival.Tumor extension, not having received chemotherapy and the caracteristics of the PF were factors related to the risk of death in all MPE patients analyzed.  FIS-FEDER PI081100, Conselleria de Sanidade PS08/18, SOGAPAR 2007, Intensification activity from FIS