tbuckley/cabot-search huggingface dataset:
Enhancing Fraction Predicts Clinical Outcome following First-Line Chemotherapy in Patients with Epithelial Ovarian Carcinoma
Authors: James P.B. O'Connor, Gordon C. Jayson, Alan Jackson, Dana Ghiorghiu, Bernadette M. Carrington, Chris J. Rose, Samantha J. Mills, Ric Swindell, Caleb Roberts, Claire L. Mitchell, Geoffrey J.M. Parker
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To define a simple radiologic biomarker of prognosis in patients with advanced epithelial ovarian carcinoma on first-line chemotherapy. Experimental Design: Twenty-seven patients receiving platinum-based chemotherapy with &amp;gt;2 cm residual disease [International Federation of Gynecology and Obstetrics (FIGO) stages IIIC or IV] after surgery were identified. The proportion of enhancing tumor tissue—the enhancing fraction—was calculated on pre-chemotherapy computed tomography scans at four Hounsfield unit (HU) thresholds and assessed for correlation with CA125 response, Response Evaluation Criteria in Solid Tumors (RECIST) radiologic response, and time to progression. Discriminative power was assessed by leave-one-out discriminant analysis. Results: Pre-chemotherapy residual tumor volume did not correlate with clinical outcome. Pre-chemotherapy enhancing fraction at all thresholds significantly correlated with CA125 response (P &amp;lt; 0.001, ρ = 0.553 for 50 HU; P &amp;lt; 0.001, ρ = 0.565 for 60 HU; P &amp;lt; 0.001, ρ = 0.553 for 70 HU; P = 0.001, ρ = 0.516 for 80 HU). Significant correlations were also shown for radiologic response at all thresholds. Enhancing fraction predicted CA125 response with 81.9% to 86.4% specificity and Response Evaluation Criteria in Solid Tumors response with 74.9% to 76.8% specificity at 95% sensitivity (dependent on threshold). Enhancing fraction correlated with time to progression at the 60 HU (P = 0.045, ρ = 0.336) and 70 HU (P = 0.042; ρ = 0.340) thresholds. Conclusion: Pre-chemotherapy enhancing fraction is a simple quantitative radiologic measure. Further evaluation in larger trials is required to confirm the potential of enhancing fraction as a predictive factor, particularly for patients who may benefit from the addition of antiangiogenic therapy.
Progress in Genetic Studies of Pain and Analgesia
Authors: Michael L. LaCroix-Fralish, Jeffrey S. Mogil
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Interindividual variability in pain sensitivity and the response to analgesic manipulations remains a considerable clinical challenge as well as an area of intense scientific investigation. Techniques in this field have matured rapidly so that much relevant data have emerged only in the past few years. Our increasing understanding of the genetic mediation of these biological phenomena have nonetheless revealed their surprising complexity. This review provides a comprehensive picture and critical analysis of the field and its prospects.
Weight Loss in Type 2 Diabetic Patients
Authors: F. Xavier Pi-Sunyer
Journal: Diabetes Care (2005)

A guiding principle in the treatment of type 2 diabetic patients has been the recommendation to lose weight (1,2). This is because the health benefits of weight loss have long been recognized (3). As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in glycosylated hemoglobin (4,5).

Redmon et al. (6) report in this issue of Diabetes Care the 2-year outcome of a combination of weight loss therapies in type 2 diabetic patients. The end result was a weight loss of 4.6 kg sustained over 2 years, which led to a decrease of HbA1c of 0.5%. While full credit must be given to the authors for their innovative approach, and for their hard and dedicated work, it is disappointing that such a combination therapy program in an excellent medical center with outstanding clinicians and facilities could not lead to a greater weight loss and particularly a greater improvement in blood glucose control.

Why is weight loss in obese diabetic patients so modest? Here, as mentioned, in the best of hands, patients who started at a weight of 113.2 kg ended 2 years later at a weight of 108.6, a 4% drop. Why can’t we do better, all of us, in treating type 2 diabetic patients?

Therapeutic weight loss in type 2 diabetic patients has been very difficult to achieve. In an 18-month study that compared the use of three sets …
The Cost of Assisted Outpatient Treatment: Can It Save States Money?
Authors: Jeffrey W. Swanson, Richard A. Van Dorn, Marvin S. Swartz, Pamela Clark Robbins, Henry J. Steadman, Thomas G. McGuire, John Monahan
Journal: American Journal of Psychiatry (2013)

The authors assessed a state's net costs for assisted outpatient treatment, a controversial court-ordered program of community-based mental health services designed to improve outcomes for persons with serious mental illness and a history of repeated hospitalizations attributable to nonadherence with outpatient treatment.A comprehensive cost analysis was conducted using 36 months of observational data for 634 assisted outpatient treatment participants and 255 voluntary recipients of intensive community-based treatment in New York City and in five counties elsewhere in New York State. Administrative, budgetary, and service claims data were used to calculate and summarize costs for program administration, legal and court services, mental health and other medical treatment, and criminal justice involvement. Adjusted effects of assisted outpatient treatment and voluntary intensive services on total service costs were examined using multivariate time-series regression analysis.In the New York City sample, net costs declined 43% in the first year after assisted outpatient treatment began and an additional 13% in the second year. In the five-county sample, costs declined 49% in the first year and an additional 27% in the second year. Psychotropic drug costs increased during the first year after initiation of assisted outpatient treatment, by 40% and 44% in the city and five-county samples, respectively. Regression analyses revealed significant declines in costs associated with both assisted outpatient treatment and voluntary participation in intensive services, although the cost declines associated with assisted outpatient treatment were about twice as large as those seen for voluntary services.Assisted outpatient treatment requires a substantial investment of state resources but can reduce overall service costs for persons with serious mental illness. For those who do not qualify for assisted outpatient treatment, voluntary participation in intensive community-based services may also reduce overall service costs over time, depending on characteristics of the target population and local service system.
Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis
Authors: M. Asbridge, J. A. Hayden, J. L. Cartwright
Journal: BMJ (2012)

<b>Objective</b> To determine whether the acute consumption of cannabis (cannabinoids) by drivers increases the risk of a motor vehicle collision. <b>Design</b> Systematic review of observational studies, with meta-analysis. <b>Data sources</b> We did electronic searches in 19 databases, unrestricted by year or language of publication. We also did manual searches of reference lists, conducted a search for unpublished studies, and reviewed the personal libraries of the research team. <b>Review methods</b> We included observational epidemiology studies of motor vehicle collisions with an appropriate control group, and selected studies that measured recent cannabis use in drivers by toxicological analysis of whole blood or self report. We excluded experimental or simulator studies. Two independent reviewers assessed risk of bias in each selected study, with consensus, using the Newcastle-Ottawa scale. Risk estimates were combined using random effects models. <b>Results</b> We selected nine studies in the review and meta-analysis. Driving under the influence of cannabis was associated with a significantly increased risk of motor vehicle collisions compared with unimpaired driving (odds ratio 1.92 (95% confidence interval 1.35 to 2.73); P=0.0003); we noted heterogeneity among the individual study effects (I<sup>2</sup>=81). Collision risk estimates were higher in case-control studies (2.79 (1.23 to 6.33); P=0.01) and studies of fatal collisions (2.10 (1.31 to 3.36); P=0.002) than in culpability studies (1.65 (1.11 to 2.46); P=0.07) and studies of non-fatal collisions (1.74 (0.88 to 3.46); P=0.11). <b>Conclusions</b> Acute cannabis consumption is associated with an increased risk of a motor vehicle crash, especially for fatal collisions. This information could be used as the basis for campaigns against drug impaired driving, developing regional or national policies to control acute drug use while driving, and raising public awareness.
Prevalence and incidence of systemic sclerosis in southern Sweden: population-based data with case ascertainment using the 1980 ARA criteria and the proposed ACR-EULAR classification criteria
Authors: K Andréasson, T Saxne, C Bergknut, R Hesselstrand, M Englund
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To estimate the prevalence and incidence of systemic sclerosis (SSc) in southern Sweden. <h3>Methods</h3> In Skåne, the southernmost region of Sweden (total population 1.2 million), healthcare provided is registered in the Skåne Healthcare Register. We identified all Skåne residents who had received an International Classification of Diseases 10 diagnosis of SSc (M34) or Raynaud9s phenomenon (I73.0) between 1998 and 2010. Every single case was ascertained by review of medical records in reference to the 1980 American Rheumatism Association preliminary classification criteria for SSc and the proposed American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria presented at the ACR/Association of Rheumatology Health Professionals Annual Meeting 2012. We calculated the point prevalence by the end of 2010 by linkage with the population register to exclude deceased persons and we also estimated the mean annual cumulative incidence for 2006–2010. <h3>Results</h3> Using the 1980 ARA criteria, the adult prevalence and annual incidence of SSc in the Skåne region were 235 and 14 per 1 million inhabitants respectively. Applying the proposed ACR-EULAR criteria, the corresponding figures were 305 and 19 per 1 million inhabitants. A majority (82%) of the prevalent cases had the limited cutaneous SSc subtype. <h3>Conclusions</h3> The prevalence and incidence of SSc in southern Sweden, based on the 1980 ARA criteria, are higher than previously reported in northern Europe and do not support the concept of a north-south gradient of SSc occurrence in Europe. Application of the proposed ACR-EULAR classification criteria in this population results in about 30–40% higher estimates of SSc prevalence and incidence compared to the 1980 ARA criteria.
Multimodal imaging in Alzheimer's disease: validity and usefulness for early detection
Authors: Stefan Teipel, Alexander Drzezga, Michel J Grothe, Henryk Barthel, Gaël Chételat, Norbert Schuff, Pawel Skudlarski, Enrica Cavedo, Giovanni B Frisoni, Wolfgang Hoffmann, Jochen René Thyrian, Chris Fox, Satoshi Minoshima, Osama Sabri, Andreas Fellgiebel
Journal: The Lancet Neurology (2015)
Clinical significance of CHD1L in hepatocellular carcinoma and therapeutic potentials of virus-mediated CHD1L depletion
Authors: L. Chen, Y.-F. Yuan, Y. Li, T. H. M. Chan, B.-J. Zheng, J. Huang, X.-Y. Guan
Journal: Gut (2010)

<h3>Background</h3> Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies. It is difficult to detect early, has a high recurrence rate and is refractory to chemotherapies. Amplification of 1q21 is one of the most frequent genetic alterations in HCC. <i>CHD1L</i> is a newly identified oncogene responsible for 1q21 amplification. This study aims to investigate the role of <i>CHD1L</i> in predicting prognosis and chemotherapy response of patients with HCC, its chemoresistant mechanism and whether virus-mediated CHD1L silencing has therapeutic potentials for HCC treatment. <h3>Methods</h3> The clinical significance of <i>CHD1L</i> in a cohort of 109 HCC cases including 50 cases who received transarterial chemoembolisation treatment was assessed by clinical correlation and Kaplan–Meier analyses. A CHD1L-overexpressing cell model was generated and the mechanism of chemoresistance involving CHD1L was investigated. An adenovirus-mediated silencing method was used to knockdown <i>CHD1L</i>, and its effects on tumorigenicity and chemoresistance were investigated in vivo and in vitro. <h3>Results</h3> Overexpression of CHD1L was significantly associated with tumour microsatellite formation (p=0.045), advanced tumour stage (p=0.018), overall survival time (p=0.002), overall survival time of patients who received transarterial chemoembolisation treatment (p=0.028) and chemoresistance (p=0.020) in HCC. Interestingly, CHD1L could inhibit apoptosis induced by 5-fluorourail (5-FU) but not doxorubicin. The mechanistic study revealed that the involvement of the Nur77-mediated pathway in chemotherapeutic agent-induced apoptosis can dictate if CHD1L could confer resistance to chemotherapy. Furthermore, an adenoviral vector containing short hairpin RNAs against <i>CHD1L</i> (<i>CHD1L</i>-shRNAs) could suppress cell growth, clonogenicity and chemoresistance to 5-FU. An in vivo study found that <i>CHD1L</i>-shRNAs could inhibit xenograft tumour growth and increase the sensitivity of tumour cells to 5-FU in nude mice. <h3>Conclusions</h3> This study highlighted for the first time the prognostic value of <i>CHD1L</i> in HCC and the potential application of virus-mediated CHD1L silencing in HCC treatment.
Reply: The Beneficial Effect of Statins on Asthma Exacerbations: Another Point of View
Authors: Sze Man Tse, Ann Chen Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

hypercholesterolemia undergoing fluvastatin therapy (5).Therefore, we wish to reiterate the possible pathomechanism behind exposure to statin therapy in reducing severity and frequency of asthma attacks using lipid peroxidation in exerting an antioxidative effect on endothelial cells of the lung.
Beneficial effects of add‐on hydrochlorothiazide in rats with myocardial infarction optimally treated with quinapril
Authors: Bart Westendorp, Regien G. Schoemaker, Hendrik Buikema, Dick de Zeeuw, Frans Boomsma, Wiek H. van Gilst, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2005)
Cognitive Behavior Therapy in the Posthospitalization Treatment of Anorexia Nervosa
Authors: Kathleen M. Pike, B. Timothy Walsh, Kelly Vitousek, G. Terence Wilson, Joy Bauer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study provides what the authors believe is the first empirical evaluation of cognitive behavior therapy as a posthospitalization treatment for anorexia nervosa in adults. METHOD: After hospitalization, 33 patients with DSM-IV anorexia nervosa were randomly assigned to 1 year of outpatient cognitive behavior therapy or nutritional counseling. RESULTS: The group receiving nutritional counseling relapsed significantly earlier and at a higher rate than the group receiving cognitive behavior therapy (53% versus 22%). The overall treatment failure rate (relapse and dropping out combined) was significantly lower for cognitive behavior therapy (22%) than for nutritional counseling (73%). The criteria for “good outcome” were met by significantly more of the patients receiving cognitive behavior therapy (44%) than nutritional counseling (7%). CONCLUSIONS: Cognitive behavior therapy was significantly more effective than nutritional counseling in improving outcome and preventing relapse. To the authors’ knowledge, these data provide the first empirical documentation of the efficacy of any psychotherapy, and cognitive behavior therapy in particular, in posthospitalization care and relapse prevention of adult anorexia nervosa.
Protein Kinase D Is a Novel Mediator of Cardiac Troponin I Phosphorylation and Regulates Myofilament Function
Authors: Robert S. Haworth, Friederike Cuello, Todd J. Herron, Gereon Franzen, Jonathan C. Kentish, Mathias Gautel, Metin Avkiran
Journal: Circulation Research (2004)

Protein kinase D (PKD) is a serine kinase whose myocardial substrates are unknown. Yeast 2-hybrid screening of a human cardiac library, using the PKD catalytic domain as bait, identified cardiac troponin I (cTnI), myosin-binding protein C (cMyBP-C), and telethonin as PKD-interacting proteins. In vitro phosphorylation assays revealed PKD-mediated phosphorylation of cTnI, cMyBP-C, and telethonin, as well as myomesin. Peptide mass fingerprint analysis of cTnI by liquid chromatography-coupled mass spectrometry indicated PKD-mediated phosphorylation of a peptide containing Ser22 and Ser23, the protein kinase A (PKA) targets. Ser22 and Ser23 were replaced by Ala, either singly (Ser22Ala or Ser23Ala) or jointly (Ser22/23Ala), and the troponin complex reconstituted in vitro, using wild-type or mutated cTnI together with wild-type cardiac troponin C and troponin T. PKD-mediated cTnI phosphorylation was reduced in complexes containing Ser22Ala or Ser23Ala cTnI and completely abolished in the complex containing Ser22/23Ala cTnI, indicating that Ser22 and Ser23 are both targeted by PKD. Furthermore, troponin complex containing wild-type cTnI was phosphorylated with similar kinetics and stoichiometry (approximately 2 mol phosphate/mol cTnI) by both PKD and PKA. To determine the functional impact of PKD-mediated phosphorylation, Ca2+ sensitivity of tension development was studied in a rat skinned ventricular myocyte preparation. PKD-mediated phosphorylation did not affect maximal tension but produced a significant rightward shift of the tension-pCa relationship, indicating reduced myofilament Ca2+ sensitivity. At submaximal Ca2+ activation, PKD-mediated phosphorylation also accelerated isometric crossbridge cycling kinetics. Our data suggest that PKD is a novel mediator of cTnI phosphorylation at the PKA sites and may contribute to the regulation of myofilament function.
Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia
Authors: S. I. Berney, C. D. Ridler, A. D. Stephens, A. E. Thomas, I. B. Kovacs
Journal: American Journal of Hematology (1992)

A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso-occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA.
Functional reconstitution, membrane targeting, genomic structure, and chromosomal localization of a human urate transporter
Authors: Michael S. Lipkowitz, Edgar Leal-Pinto, Joshua Z. Rappoport, Vesna Najfeld, Ruth G. Abramson
Journal: Journal of Clinical Investigation (2001)

Elevated serum levels of uric acid have been associated with an increased risk for gout, hypertension, cardiovascular disease, and renal failure. The molecular mechanisms for the diminished excretion of urate in these disorders, however, remain poorly understood. Human galectin 9, which is highly homologous to the rat urate transporter rUAT, has been reported to be a secreted or cytosolic protein. We provide data that galectin 9 is hUAT, the first identified human urate transporter. hUAT is a highly selective urate ion channel when inserted in lipid bilayers. When expressed in renal epithelial cells it is an integral plasma membrane protein with at least two transmembrane domains. The gene for hUAT consists of 11 exons and is mapped to chromosome 17; a highly homologous gene, hUAT2, maps to a nearby region of chromosome 17 and is also likely to be a urate transporter. hUAT is expressed in a wide variety of tissues and is present in at least three isoforms; hUAT2 is less widely expressed at severalfold lower levels than hUAT. Further knowledge about the functions of hUAT, its isoforms, and hUAT2, as well as mutational analysis of hUAT1 and hUAT2 in individuals or families with hyperuricemia, should significantly improve our understanding of the molecular mechanisms of urate homeostasis.
Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.
Authors: S L Schantz, D M Gasior, E Polverejan, R J McCaffrey, A M Sweeney, H E Humphrey, J C Gardiner
Journal: Environmental Health Perspectives (2001)

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.