tbuckley/cabot-search huggingface dataset:
The introduction of QF-PCR in prenatal diagnosis of fetal aneuploidies: time for reconsideration
Authors: Umberto Nicolini, Faustina Lalatta, Federica Natacci, Cristina Curcio, The-Hung Bui
Journal: Human Reproduction Update (2004)

Quantitative fluorescent polymerase chain reaction (QF-PCR) has recently entered the field of prenatal diagnosis to overcome the need to culture fetal cells, hence to allow rapid diagnosis of some selected chromosomal anomalies. We reviewed the studies on the accuracy of QF-PCR in detecting chromosomal anomalies at prenatal diagnosis. Overall, 22 504 samples have been analysed. The detection rate of aneuploidies of the selected chromosomes (13, 18 and 21, and X and Y) was 98.6% (95% confidence interval 97.8-99.3). QF-PCR might play a major role and be considered a valid alternative to the full karyotype. Being less expensive, and almost entirely automated, more women could undergo invasive prenatal diagnosis without significant increase in health expenditure. By using QF-PCR as a stand-alone test, the chances of non diagnosing the commonest, and the only chromosome anomalies which do increase in frequency with maternal age, are approximately one in 150 abnormal karyotypes, or one in 10-30 000 samples, based on the age distribution. These error rates might be deemed acceptable, although most structural chromosomal anomalies will be missed. At present, women are rarely informed about the full spectrum of the conditions which might be diagnosed via amniocentesis or chorionic villous sampling. Some of these anomalies might be acceptable, in view of their limited or uncertain clinical relevance, and decision analysis might, in the majority of cases, confine the full karyotype to selected women who have specific indications.
The Development of Alcohol Use Disorders
Authors: Kenneth J. Sher, Emily R. Grekin, Natalie A. Williams
Journal: Annual Review of Clinical Psychology (2004)

Pathological alcohol use is a complex and costly problem. This chapter focuses on recent developments in the etiology of alcohol use disorders. Literature is reviewed from the fields of epidemiology, genetics, personality, neuropsychology, parenting, and social influences. In addition, theoretical models that describe pathways to the development of alcohol use disorders are presented. Particular emphasis is given to ways in which genetic, environmental, psychopharmacological, and personological literatures can inform one another.
Identification of Tumor Evolution Patterns by Means of Inductive Logic Programming
Authors: Vitoantonio Bevilacqua, Patrizia Chiarappa, Giuseppe Mastronardi, Filippo Menolascina, Angelo Paradiso, Stefania Tommasi
Journal: Genomics Proteomics & Bioinformatics (2008)

In considering key events of genomic disorders in the development and progression of cancer, the correlation between genomic instability and carcinogenesis is currently under investigation. In this work, we propose an inductive logic programming approach to the problem of modeling evolution patterns for breast cancer. Using this approach, it is possible to extract fingerprints of stages of the disease that can be used in order to develop and deliver the most adequate therapies to patients. Furthermore, such a model can help physicians and biologists in the elucidation of molecular dynamics underlying the aberrations-waterfall model behind carcinogenesis. By showing results obtained on a real-world dataset, we try to give some hints about further approach to the knowledge-driven validations of such hypotheses.
Irinotecan Plus Oxaliplatin and Leucovorin-Modulated Fluorouracil in Advanced Pancreatic Cancer—A Groupe Tumeurs Digestives of the Fédération Nationale des Centres de Lutte Contre le Cancer Study
Authors: Thierry Conroy, Bernard Paillot, Eric François, Roland Bugat, Jacques-Henri Jacob, Ulrich Stein, Salvador Nasca, Jean-Philippe Metges, Olivier Rixe, Pierre Michel, Emmanuelle Magherini, Aliette Hua, Gael Deplanque
Journal: Journal of Clinical Oncology (2005)

To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA).Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL.With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial.
T Cell Receptor (Tcr)-Mediated Repertoire Selection and Loss of Tcr Vβ Diversity during the Initiation of a Cd4+ T Cell Response in Vivo
Authors: Marcella Fassò, Niroshana Anandasabapathy, Frances Crawford, John Kappler, C. Garrison Fathman, William M. Ridgway
Journal: The Journal of Experimental Medicine (2000)

We recently described a novel way to isolate populations of antigen-reactive CD4+ T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS® sorting by CD4high expression. Phenotypic, FACS®, functional, antibody inhibition, and major histocompatibility complex–peptide tetramer analyses, as well as T cell receptor Vβ sequence analyses, of the antigen-specific CD4high T cell populations demonstrated that a diverse sperm whale myoglobin 110–121–reactive CD4+ T cell repertoire was activated at the beginning (day 3 after immunization) of the immune response. Within 6 d of immunization, lower affinity clones were lost from the responding population, leaving an expanded population of oligoclonal, intermediate affinity (and residual high affinity) T cells. This T cell subset persisted for at least 4 wk after immunization and dominated the secondary immune response. These data provide evidence that CD4+ T cell repertoire selection occurs early in the immune response in vivo and suggest that persistence and expansion of a population of oligoclonal, intermediate affinity T cells is involved in CD4+ T cell memory.
Comparison of terbutaline, isotonic saline, ambient air and non-treatment in patients with reversible chronic airway obstruction
Authors: O May, NC Hansen
Journal: European Respiratory Journal (1988)

The increase in forced expiratory volume in one second (FEV1) seen in asthmatics after inhalation of isotonic saline was studied in a blind, cross-over investigation of 24 consecutive out-patients presenting with reversible chronic airway obstruction. Forced expiratory manoeuvres allowing the measurement of FEV1 and forced vital capacity (FVC) were performed at six time intervals during a period of one hour according to the following regimes: inhalation of terbutaline by means of a Pari-inhalier Boy for 10 min; inhalation of isotonic saline under the same conditions; inhalation of ambient air under the same conditions (placebo with noisy nebulizer); inhalation of air without the nebulizer (non-treatment) in order to determine whether the impact of treatment by a nebulizer influences the measured lung function. A statistically significant increase in FEV1 was observed after each of the four regimes. The increase was large following terbutaline inhalation. After the other three regimes, it was significantly smaller and of about the same magnitude in each case. The increase in FEV1 after the non-treatment regime was unexpected and could possibly be due to the repeated dynamic spirometry. The increase in FEV1 after isotonic saline and ambient air (noisy nebulizer) did not differ from the increase after the non-treatment regime. We conclude that neither isotonic saline nor the impact of treatment with a noisy nebulizer have a measurable effect on lung function.
Improvement of Peripheral Endothelial Dysfunction by Protein Tyrosine Phosphatase Inhibitors in Heart Failure
Authors: Magali Vercauteren, Elise Remy, Corinne Devaux, Brigitte Dautreaux, Jean-Paul Henry, Fabrice Bauer, Paul Mulder, Rob Hooft van Huijsduijnen, Agnès Bombrun, Christian Thuillez, Vincent Richard
Journal: Circulation (2006)

Chronic heart failure (CHF) induces endothelial dysfunction characterized by a decrease in nitric oxide (NO) production in response to flow (flow-mediated dilatation [FMD]). Because activation of endothelial NO synthase (eNOS) by flow requires tyrosine phosphorylation, we tested whether endothelial dysfunction could be corrected by increasing phosphotyrosine levels using protein tyrosine phosphatase (PTP) inhibitors and especially inhibitors of PTP1B.CHF was induced by coronary ligation in mice, and FMD was assessed in isolated and cannulated mesenteric artery segments (2 mm in length and <300 microm in diameter). CHF almost abolished FMD but only moderately affected the response to acetylcholine. In mice with CHF, the PTP1B inhibitors AS279, AS098, and AS713 restored FMD to levels similar to those of normal mice. This restoration was reduced by inhibitors of eNOS and phosphatidylinositol-3 kinase. Polymerase chain reaction and Western blot showed that arteries express PTP1B, and this expression was not affected by CHF. Immunolocalization revealed the presence of PTP1B in the endothelium and the adventitia. Flow induced a transient eNOS phosphorylation that was absent in CHF. PTP1B inhibition stimulated early eNOS phosphorylation and increased phosphorylation of Akt.Our results demonstrate for the first time that PTP1B inhibitors may be potent treatments for endothelial dysfunction.
Nonalcoholic Fatty Liver Disease Is Independently Associated With an Increased Incidence of Cardiovascular Events in Type 2 Diabetic Patients
Authors: Giovanni Targher, Lorenzo Bertolini, Stefano Rodella, Roberto Tessari, Luciano Zenari, Giuseppe Lippi, Guido Arcaro
Journal: Diabetes Care (2007)

Recent data suggest that the presence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes may be linked to increased cardiovascular disease (CVD) independent of components of the metabolic syndrome (1–3), although this hypothesis needs verification in larger studies. We assessed whether NAFLD, as diagnosed by ultrasound, predicts the risk of incident CVD events in a large cohort of type 2 diabetic adults.

Study subjects were participants in the Valpolicella Heart Diabetes Study (1). Briefly, we enrolled all of the type 2 diabetic outpatients ( n = 2,103) who regularly attended our clinic in the period January–December 2000 after excluding those who had manifest CVD and/or secondary causes of chronic liver disease (alcohol abuse, viral infection, or medications). The local ethics committee approved the study. All participants provided written informed consent.

During 6.5 years of follow-up (through December 2006; follow-up range: 5–84 months), 384 participants subsequently developed CVD events (myocardial infarction, ischemic stroke, coronary revascularization, or cardiovascular death), whereas 1,719 patients remained free of diagnosed CVD. These events were ascertained by patient history, chart review, autopsy reports, and family contact (1).

Plasma liver enzymes, A1C, and other biochemical blood measurements were determined by standard procedures. At baseline, most participants (∼86%) had normal liver enzymes (reference ranges for aminotransferases were 10–35 and 10–50 units/l for female and male subjects, respectively) and were abstainers (77%) or drank minimally (13%); only 10% of participants …
Efficacy and safety of 15(R/S)-methyl-lipoxin A<sub>4</sub>in topical treatment of infantile eczema
Authors: S.-H. Wu, X.-Q. Chen, B. Liu, H.-J. Wu, L. Dong
Journal: British Journal of Dermatology (2012)

Lipoxins are potential anti-inflammatory mediators and serve as an endogenous 'braking signal' in the inflammatory process. Accumulating evidence has indicated the efficacy of lipoxin A(4) (LXA(4) ) and its analogs in the treatment of many animal models of inflammatory diseases. This study investigates the efficacy and safety of 15(R/S)-methyl-lipoxin A(4) in the topical treatment of infantile eczema.In this two-centre, double-blind, placebo-controlled, randomized, parallel-groups comparative study, 60 patients were randomly assigned to receive either the 15(R/S)-methyl-lipoxin A(4) cream, mometasone furoate (Eloson, Schering-Plough, Shanghai, China) or placebo for 10days. The efficacy was determined using the Severity Scale Score (SSS), Eczema Area and Severity Index (EASI) and the Infants' Dermatitis Quality of Life Index (IDQOL). Safety was monitored by physical examination, laboratory investigation and documentation of clinical adverse events. The treatment of eczema with 15(R/S)-methyl-LXA(4) cream significantly relieved the severity, induced a recovery, and improved the quality of life of the patients, as demonstrated by significantly reduced SSS, EASI and IDQOL, respectively, in a way similar to the efficacy of Eloson. All safety parameters remained within normal limits. No clinical adverse event was found in the three patient groups. 15(R/S)-methyl-LXA(4) was well tolerated, and significantly reduced the severity of eczema. The results of this small exploratory study suggest that 15(R/S)-methyl-LXA(4) warrants further investigation in the treatment of eczema.
A Comparative and Integrative Approach Identifies <i>ATPase Family, AAA Domain Containing 2</i> as a Likely Driver of Cell Proliferation in Lung Adenocarcinoma
Authors: Robert Fouret, Julien Laffaire, Paul Hofman, Michèle Beau-Faller, Julien Mazieres, Pierre Validire, Philippe Girard, Sophie Camilleri-Bröet, Fabien Vaylet, François Leroy-Ladurie, Jean-Charles Soria, Pierre Fouret
Journal: Clinical Cancer Research (2012)

To identify genetic changes that could drive cancer pathogenesis in never and ever smokers with lung adenocarcinoma.We analyzed the copy number and gene expression profiles of lung adenocarcinomas in 165 patients and related the alterations to smoking status. Having found differences in the tumor profiles, we integrated copy number and gene expression data from 80 paired samples.Amplifications at 8q24.12 overlapping MYC and ATAD2 were more frequent in ever smokers. Unsupervised analysis of gene expression revealed two groups: in the group with mainly never smokers, the tumors expressed genes common to normal lung; in the group with more ever smokers, the tumors expressed "proliferative" and "invasive" gene clusters. Integration of copy number and gene expression data identified one module enriched in mitotic genes and MYC targets. Its main associated modulator was ATAD2, a cofactor of MYC. A strong dose-response relationship between ATAD2 and proliferation-related gene expression was noted in both never and ever smokers, which was verified in two independent cohorts. Both ATAD2 and MYC expression correlated with 8q24.12 amplification and were higher in ever smokers. However, only ATAD2, and not MYC, overexpression explained the behavior of proliferation-related genes and predicted a worse prognosis independently of disease stage in a large validation cohort.The likely driving force behind MYC contribution to uncontrolled cell proliferation in lung adenocarcinoma is ATAD2. Deregulation of ATAD2 is mainly related to gene amplification and is more frequent in ever smokers.
Prolymphocytic leukemia treated with natural and recombinant α‐interferon
Authors: Takeshi Terashima, Ken‐Ichi Ohtake, Tetsuhei Ogawa
Journal: American Journal of Hematology (1990)

Abstract The patient was a 65 year old woman with a massive splenomegaly and no lymphoadenopathy. An electron microscopic study of the peripheral blood cells revealed that these cells were prolymphocytes with a single large nucleolus. Treatment with native and recombinant α‐interferon has produced an impressive reduction in spleen size and in the count of prolymphocytes.
Review calls for major changes to care of older people to restore dignity
Authors: A. O'Dowd
Journal: BMJ (2012)

A major cultural shift is needed in health and social care services to guarantee older people the dignity they deserve but often don’t get, concludes a major review published on 18 June.

Changing the way that the NHS, the independent sector, and social care services design, fund, deliver, and monitor services for older people is essential, concludes the report, Delivering Dignity , the final report from the Commission on Improving Dignity in Care for Older People.1 The commission is an independent group set up by the NHS Confederation, the charity Age UK, and the Local Government Association, which published a draft report on these issues in February.2

The commission was set up in July last year after the publication in February …
MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study
Authors: David S Hong, David Hui, Eduardo Bruera, Filip Janku, Aung Naing, Gerald S Falchook, Sarina Piha-Paul, Jennifer J Wheler, Siqing Fu, Apostolia M Tsimberidou, Michael Stecher, Prasant Mohanty, John Simard, Razelle Kurzrock
Journal: The Lancet Oncology (2014)
Prevalence of asthma among 12 year old children in New Zealand and South Wales: a comparative survey.
Authors: D M Barry, M L Burr, E S Limb
Journal: Thorax (1991)

A survey of 12 year old schoolchildren was carried out in New Zealand and South Wales, the same questionnaire and exercise provocation test being used. The prevalence of a history of asthma at any time was higher in New Zealand (147/873, 17%) than in South Wales (116/965, 12%). The New Zealand children were also more likely than the Welsh children to have a history of "wheeze ever" (27% versus 22%), and wheeze brought on by running (15% versus 10.5%). The sex ratio of asthmatic and wheezy children was very similar in the two countries. A history of hospital admission for chest trouble was twice as common in New Zealand as in South Wales. An exercise test produced a fall in peak expiratory flow rate of 15% or more in more New Zealand children (12.2%) than Welsh children (7.7%). These results suggest that the prevalence of childhood asthma is higher in New Zealand than in South Wales.
Studies of the pituitary-Leydig cell axis in young men with hypogonadotropic hypogonadism and hyposmia: comparison with normal men, prepuberal boys, and hypopituitary patients
Authors: C. Wayne Bardin, Griff T. Ross, Arleen B. Rifkind, Charles M. Cargille, Mortimer B. Lipsett
Journal: Journal of Clinical Investigation (1969)

Pituitary and gonadal function was studied in seven chromatin-negative men, ages 15-27 yr, with retarded sexual and somatic development, skeletal anomalies, and hyposmia. These hyposmic patients were compared with normal men, prepuberal boys and hypogonadal patients with hypopituitarism. The urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels of hyposmic subjects were the same as those of normal boys and hypopituitary patients but significantly lower than those of normal men. Clomiphene citrate did not cause an increase in plasma FSH and LH levels in either hypogonadal group as it does in normal men. In contrast to hypopituitary patients, thyroid and adrenocortical function and release of growth hormone in the hyposmic subjects were normal. The plasma testosterone levels were equally low in prepuberal, hypopituitary, and hyposmic patients but were increased to a greater extent by human chorionic gonadotropin (HCG) treatment in prepuberal and hypopituitary subjects than in the hyposmic patients. Prolonged treatment with HCG has failed to return plasma testosterone levels to normal in two hyposmic patients. These observations suggest that there are defects of both pituitary and Leydig cell function in men with the syndrome of hypogonadism, skeletal anomalies, and hyposmia. They have impaired secretion of FSH and LH and a Leydig cell insensitivity to gonadotropin.
Some Lessons for the Future from the Global Malaria Eradication Programme (1955–1969)
Authors: José A. Nájera, Matiana González-Silva, Pedro L. Alonso
Journal: PLoS Medicine (2011)

Encouraged by the early success of using dichloro-diphenyl-trichloroethane (DDT) against malaria, the World Health Organization (WHO) embarked on the Global Malaria Eradication Program (GMEP) in 1955. Fourteen years later, the campaign was discontinued when it was recognised that eradication was not achievable with the available means in many areas, although the long-term goal remained unchanged. During the GMEP, malaria was permanently eliminated from many regions. In other areas, however, substantial gains were lost in resurgences, sometimes of epidemic proportions. During the 1970s and 1980s, because of economic and financial crises, international support for malaria control declined rapidly, but in the past decade, following increasing demands from endemic countries and promising results from scaling up of control activities, interest in malaria elimination and the long-term goal of eradication has received international political and financial support. In 2007, there was a renewed call for malaria eradication and a consultative process to define a research and development agenda for malaria eradication (malERA) was established. Lessons learned from the GMEP (1955–1969) highlight the fact that no single strategy can be applicable everywhere and that a long-term commitment with a flexible strategy that includes community involvement, integration with health systems, and the development of agile surveillance systems is needed.
Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel and weekly gemcitabine: A phase II trial
Authors: C.H. Spiridonidis, L.R. Laufman, L. Carman, T. Moore, S. Blair, J. Jones, Ch. George, T. Patel, R. Roach, R. Rupert, J. Zangmeister, D. Colborn, J.Ph. Kuebler
Journal: Annals of Oncology (2001)