tbuckley/cabot-search huggingface dataset:
OncoSurge: A Strategy for Improving Resectability With Curative Intent in Metastatic Colorectal Cancer
Authors: Graeme J. Poston, René Adam, Steven Alberts, Steven Curley, Juan Figueras, Daniel Haller, Francis Kunstlinger, Gilles Mentha, Bernard Nordlinger, Yehuda Patt, John Primrose, Mark Roh, Philippe Rougier, Theo Ruers, Hans Joachim Schmoll, Carlos Valls, Nick Jean-Nicolas Vauthey, Marleen Cornelis, James P. Kahan
Journal: Journal of Clinical Oncology (2005)

Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences.We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes.Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of < or = 4 or > 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of < or = 4 metastases and unilobar liver involvement. Resection was appropriate only for > 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation.The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.
Intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis
Authors: Y. Okuda, K. Takasugi, T. Oyama, H. Oyama, S. Nanba, T. Miyamoto
Journal: Annals of the Rheumatic Diseases (1997)

To examine the clinical characteristics of intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis (RA).Of 179 RA patients with biopsy confirmed secondary amyloidosis, 24 cases (23 women and one man) with intractable diarrhoea lasting for more than one month were retrospectively evaluated.The mean (SD) duration of diarrhoea was 87 (64) days. Prodromal symptoms of gastrointestinal dysfunction (n = 21) and impaired peristalsis (n = 16) were observed. Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl) caused by malabsorption or protein loss and high values of C reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable diarrhoea (n = 4) and transition from intractable diarrhoea to other gastrointestinal problems of amyloidosis (ischaemic colitis (n = 2) and intestinal pseudo-obstruction (n = 4)) were observed. In 19 patients (25 episodes) the duration of intravenous hyperalimentation at remission (18 episodes) was 68 (52) days. Corticosteroid pulse therapy was administered to 10 patients (11 times) and the time elapsed from the end of corticosteroid pulse therapy to the end of diarrhoea was 18 (14) days. One and five year survival rates after the onset of intractable diarrhoea were 73.4% and 38.9%. Seven of 13 patients (54%) had died as a result of infectious diseases.Intractable diarrhoea associated with secondary amyloidosis in RA is a serious clinical entity and the prognosis is poor. Although it is assumed that intravenous hyperalimentation treatment and corticosteroid pulse therapy are favourable regimens for intractable diarrhoea, the patients should be monitored for possible infectious complications.
Pathways to perinatal depressive symptoms after mass conflict in Timor-Leste: a modelling analysis using cross-sectional data
Authors: Derrick Silove, Susan Rees, Alvin Kuowei Tay, Zelia Maria da Costa, Elisa Soares Savio, Cesarina Soares, Wietse Tol
Journal: The Lancet Psychiatry (2015)
Continuous deep sedation for patients nearing death in the Netherlands: descriptive study
Authors: Judith Rietjens, Johannes van Delden, Bregje Onwuteaka-Philipsen, Hilde Buiting, Paul van der Maas, Agnes van der Heide
Journal: BMJ (2008)

<b>Objectives</b> To study the practice of continuous deep sedation in 2005 in the Netherlands and compare it with findings from 2001. <b>Design</b> Questionnaire study about random samples of deaths reported to a central death registry in 2005 and 2001. <b>Setting</b> Nationwide physician study in the Netherlands. <b>Participants</b> Reporting physicians received a questionnaire about the medical decisions that preceded the patient’s death; 78% (n=6860) responded in 2005 and 74% (n=5617) in 2001. <b>Main outcome measures</b> Characteristics of continuous deep sedation (attending physician, types of patients, drugs used, duration, estimated effect on shortening life, palliative consultation). Requests for euthanasia. <b>Results</b> The use of continuous deep sedation increased from 5.6% (95% confidence interval 5.0% to 6.2%) of deaths in 2001 to 7.1% (6.5% to 7.6%) in 2005, mostly in patients treated by general practitioners and in those with cancer (in 2005, 47% of sedated patients had cancer <i>v</i> 33% in 2001). In 83% of cases sedation was induced by benzodiazepines, and in 94% patients were sedated for periods of less than one week until death. Nine per cent of those who received continuous deep sedation had previously requested euthanasia but their requests were not granted. Nine per cent of the physicians had consulted a palliative expert. <b>Conclusions</b> The increased use of continuous deep sedation for patients nearing death in the Netherlands and the limited use of palliative consultation suggests that this practice is increasingly considered as part of regular medical practice.
COPD causation and workplace exposures; an assessment of annual FEV1 decline significance between expert clinical raters
Authors: David Fishwick, Anthony Darby, Chris Barber, Andrew Curran, Paul Blanc
Journal: European Respiratory Journal (2011)

Objectives:  Epidemiological studies identify that 10-15% of the burden of chronic obstructive pulmonary disease (COPD) is attributable to inhaled occupational exposures. Despite this knowledge, very little is known about how clinicians weight this contribution against other risks.   Methods:  15 hypothetical cases of COPD were structured to represent a broad range of smoking and occupational exposure histories. Twelve clinical experts in COPD and 12 clinical experts in occupational lung disease (OLD) were invited to rate the causes of COPD in each case. Cases were developed  a priori  into 9 categories; combinations of low, medium and high tobacco smoking and low, medium, and high COPD-risk occupational exposures. Five cases also contained annual FEV 1  decline data, and raters were asked to comment about its significance, and any required actions. These latter five cases represented annual FEV 1  declines of between 95mls to 400mls a year.   Results:  Responses were received from 14 raters (9 OLD and 5 COPD), representing a 58% response. Significant variation was seen when assessing the relevance of various declines in FEV 1 . In particular, there were differences in approach to identifying significant or concerning decline, and similarly different advice concerning the risks of continuing employment.   Conclusion:  There was a wide range of estimates relating to causative factors in COPD documented by experienced clinical raters, and a variance of view relating to annual decline in FEV 1 . An improved evidence base is required to help formulate practical guidance for respiratory and occupational physicians when interpreting serial measures of lung function in working groups.
Variation in the Cost of Generic Topical Corticosteroids
Authors: Alexander Skojec, Galen Foulke, Joslyn S. Kirby
Journal: JAMA Dermatology (2015)

Variation in the Cost of Generic Topical CorticosteroidsPrescription medications accounted for $307 billion in the United States in 2010, or about 12% of all US health care spending.Prescribing generic rather than brand-name medications, including topical medications, has been encouraged as a way to curb spending on prescription medications.In fact, the growth of spending on prescription medication has decreased in association with increased use of generic drugs. 1 However, practitioners and patients can be frustrated by the affordability of even older generic medications. 2This paradoxical situation came to light with the shortage, and subsequent increased cost, of doxycycline hydrochloride in 2013.Recently, we had many patients experience a high cost for topical clobetasol propionate; we undertook this study to investigate the variation in costs of generic topical corticosteroids of various potencies.
Identification of Novel Long Noncoding RNAs Underlying Vertebrate Cardiovascular Development
Authors: Leo Kurian, Aitor Aguirre, Ignacio Sancho-Martinez, Christopher Benner, Tomoaki Hishida, Thai B. Nguyen, Pradeep Reddy, Emmanuel Nivet, Marie N. Krause, David A. Nelles, Concepcion Rodriguez Esteban, Josep M. Campistol, Gene W. Yeo, Juan Carlos Izpisua Belmonte
Journal: Circulation (2015)

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators with important functions in development and disease. Here, we sought to identify and functionally characterize novel lncRNAs critical for vertebrate development.By relying on human pluripotent stem cell differentiation models, we investigated lncRNAs differentially regulated at key steps during human cardiovascular development with a special focus on vascular endothelial cells. RNA sequencing led to the generation of large data sets that serve as a gene expression roadmap highlighting gene expression changes during human pluripotent cell differentiation. Stage-specific analyses led to the identification of 3 previously uncharacterized lncRNAs, TERMINATOR, ALIEN, and PUNISHER, specifically expressed in undifferentiated pluripotent stem cells, cardiovascular progenitors, and differentiated endothelial cells, respectively. Functional characterization, including localization studies, dynamic expression analyses, epigenetic modification monitoring, and knockdown experiments in lower vertebrates, as well as murine embryos and human cells, confirmed a critical role for each lncRNA specific for each analyzed developmental stage.We have identified and functionally characterized 3 novel lncRNAs involved in vertebrate and human cardiovascular development, and we provide a comprehensive transcriptomic roadmap that sheds new light on the molecular mechanisms underlying human embryonic development, mesodermal commitment, and cardiovascular specification.
Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-Dependent and -Independent Mechanisms
Authors: Jagdeep K. Singh, Gillian Farnie, Nigel J. Bundred, Bruno M Simões, Amrita Shergill, Göran Landberg, Sacha J. Howell, Robert B. Clarke
Journal: Clinical Cancer Research (2012)

Breast cancer stem-like cells (CSC) are an important therapeutic target as they are predicted to be responsible for tumor initiation, maintenance, and metastases. Interleukin (IL)-8 is upregulated in breast cancer and is associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy.CSC activity of metastatic and invasive human breast cancers (n = 19) was assessed ex vivo using the mammosphere colony-forming assay.Metastatic fluid IL-8 level correlated directly with mammosphere formation (r = 0.652; P < 0.05; n = 10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n = 17). IL-8 induced activation of EGFR/HER2 and downstream signaling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, phosphoinositide 3-kinase (PI3K), or MEK. Furthermore, lapatinib, which targets EGFR/HER2, inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers.These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and show that IL-8/CXCR1/2 signaling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients.
Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines
Authors: Amy W. Chung, Musie Ghebremichael, Hannah Robinson, Eric Brown, Ickwon Choi, Sophie Lane, Anne-Sophie Dugast, Matthew K. Schoen, Morgane Rolland, Todd J. Suscovich, Alison E. Mahan, Larry Liao, Hendrik Streeck, Charla Andrews, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Mark S. de Souza, Jaranit Kaewkungwal, Punnee Pitisuttithum, Donald Francis, Nelson L. Michael, Jerome H. Kim, Chris Bailey-Kellogg, Margaret E. Ackerman, Galit Alter
Journal: Science Translational Medicine (2014)

The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.
Voxelwise atlas rating for computer assisted diagnosis: Application to congenital heart diseases of the great arteries
Authors: Maria A. Zuluaga, Ninon Burgos, Alex F. Mendelson, Andrew M. Taylor, Sébastien Ourselin
Journal: Medical Image Analysis (2015)

Atlas-based analysis methods rely on the morphological similarity between the atlas and target images, and on the availability of labelled images. Problems can arise when the deformations introduced by pathologies affect the similarity between the atlas and a patient's image. The aim of this work is to exploit the morphological dissimilarities between atlas databases and pathological images to diagnose the underlying clinical condition, while avoiding the dependence on labelled images. We propose a voxelwise atlas rating approach (VoxAR) relying on multiple atlas databases, each representing a particular condition. Using a local image similarity measure to assess the morphological similarity between the atlas and target images, a rating map displaying for each voxel the condition of the atlases most similar to the target is defined. The final diagnosis is established by assigning the condition of the database the most represented in the rating map. We applied the method to diagnose three different conditions associated with dextro-transposition of the great arteries, a congenital heart disease. The proposed approach outperforms other state-of-the-art methods using annotated images, with an accuracy of 97.3% when evaluated on a set of 60 whole heart MR images containing healthy and pathological subjects using cross validation.
Wellness, fatigue and physical performance acclimatisation to a 2-week soccer camp at 3600 m (ISA3600)
Authors: Martin Buchheit, Ben M Simpson, Laura A Garvican-Lewis, Kristal Hammond, Marlen Kley, Walter F Schmidt, Robert J Aughey, Rudy Soria, Charli Sargent, Gregory D Roach, Jesus C Jimenez Claros, Nadine Wachsmuth, Christopher J Gore, Pitre C Bourdon
Journal: British Journal of Sports Medicine (2013)

To examine the time course of wellness, fatigue and performance during an altitude training camp (La Paz, 3600 m) in two groups of either sea-level (Australian) or altitude (Bolivian) native young soccer players.Wellness and fatigue were assessed using questionnaires and resting heart rate (HR) and HR variability. Physical performance was assessed using HR responses to a submaximal run, a Yo-Yo Intermittent recovery test level 1 (Yo-YoIR1) and a 20 m sprint. Most measures were performed daily, with the exception of Yo-YoIR1 and 20 m sprints, which were performed near sea level and on days 3 and 10 at altitude.Compared with near sea level, Australians had moderate-to-large impairments in wellness and Yo-YoIR1 relative to the Bolivians on arrival at altitude. The acclimatisation of most measures to altitude was substantially slower in Australians than Bolivians, with only Bolivians reaching near sea-level baseline high-intensity running by the end of the camp. Both teams had moderately impaired 20 m sprinting at the end of the camp. Exercise HR had large associations (r>0.5-0.7) with changes in Yo-YoIR1 in both groups.Despite partial physiological and perceptual acclimatisation, 2 weeks is insufficient for restoration of physical performance in young sea-level native soccer players. Because of the possible decrement in 20 m sprint time, a greater emphasis on speed training may be required during and after altitude training. The specific time course of restoration for each variable suggests that they measure different aspects of acclimatisation to 3600 m; they should therefore be used in combination to assess adaptation to altitude.
Pulmonary actinomycosis complicating infliximab therapy for Crohn's disease
Authors: R D Cohen, W R Bowie, R Enns, J Flint, J M Fitzgerald
Journal: Thorax (2007)

The use of anti-tumour necrosis factor (TNF) agents has expanded significantly over the past few years, particularly for rheumatological diseases and Crohn's disease. A number of associated opportunistic infections have been observed as a result of suppression of T cell-mediated immunity, the most frequent being tuberculosis. We report the first case of pulmonary actinomycosis in a patient receiving regular infusions of infliximab, an anti-TNF agent, for Crohn's disease.
Seasonal Variation of Violence in Norway
Authors: Gunnar Morken, Olav M. Linaker
Journal: American Journal of Psychiatry (2000)

Seasonal variations of violence have been the subject of some controversy. Norway, situated between latitudes 58 degrees and 72 degrees N, has considerable seasonal variations of light and provides a good opportunity for studies of seasonality.The monthly numbers of police reports of violent incidents in 1991-1997 were obtained for the entire Norwegian population of 4,450,000 inhabitants and separately for each of seven Norwegian cities at different latitudes.A total of 82,537 episodes of violence were recorded. There was a significant variation in violent incidents between months, with a minimum daily frequency of 28.7 in March and a maximum daily frequency of 35.1 in June. The frequency curve had one significant peak in May through June and another significant peak in October through November. The monthly frequency of violence correlated with the absolute value of monthly change in length of day from the previous month. In the seven cities the highest monthly ratio of observed to expected frequencies increased with latitude. With increasing latitude, the months with the largest increase in violence came later both in the spring and in the fall.There is a distinct pattern of seasonal variation in the frequency of violence that varies systematically with latitude. This pattern resembles the seasonal pattern of some forms of suicide, hospitalization for affective disorders, and mood and activity in the general population.
A Pilot Study to Establish a Clinical Model to Perform Phase II Studies of Breast Cancer Chemopreventive Agents in Women at High Risk with Biomarkers as Surrogate Endpoints for Activity
Authors: Vered Stearns, Ann Gallagher, Celina G. Kleer, Baljit Singh, Matthew Freedman, Bassem R. Haddad, Claudine Isaacs, Robert Warren, Martha Brown, Jennifer Cullen, Bruce Trock, Daniel F. Hayes
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Use of surrogate end point biomarkers in phase II trials may help select agents that appear to have activity and might be evaluated in future phase III definitive trials of breast cancer prevention. We performed a pilot clinical trial to establish the logistics for a clinical model to perform phase II studies of breast cancer chemopreventive agents in women at high risk with novel imaging techniques and candidate surrogate end point biomarkers for activity. We chose tamoxifen to establish proof of principal with a known effective agent. Experimental Design: Women at a high risk of developing a new breast cancer and for whom tamoxifen was recommended were eligible. The women underwent baseline and 3 and 6 months mammogram and magnetic resonance imaging (MRI) of one breast to identify areas of water-like intensity (epithelial) and to determine the changes over time and MRI-directed core breast biopsies of these areas for surrogate end point biomarkers analysis. Results: From August 1999 to March 2001, 26 women underwent baseline imaging and core biopsies. Sixteen women took tamoxifen and 10 chose not to. Overall, 79% of the samples contained glandular tissue evaluable for histology, but only 66% of the samples were evaluable for marker analysis. Only 12 patients had specimens with glandular tissue sufficient for marker analysis both at baseline and in at least one follow-up. Because of the small number of women with matched samples, marker analysis was not informative. Conclusions: This study shows the feasibility of obtaining serial core breast biopsies from women at a high risk of developing a new breast cancer. Patient participation in this model is satisfactory, and such a model may provide indication of drug activity. MRI-directed biopsy did not provide a high yield of evaluable samples, and additional work on adequate collection of epithelial tissue for surrogate end point biomarker analysis is thus necessary.