tbuckley/cabot-search huggingface dataset:
High frequency ultrasound measurement of digital dermal thickness in systemic sclerosis
Authors: Olga Kaloudi, Francesca Bandinelli, Emilio Filippucci, Maria Letizia Conforti, Irene Miniati, Serena Guiducci, Francesco Porta, Antonio Candelieri, Domenico Conforti, Genesio Grassiri, Walter Grassi, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2009)

Currently, assessment of dermal thickness in systemic sclerosis (SSc) is performed by palpation and assessment using the modified Rodnan skin score (mRSS).To verify whether high frequency ultrasound (US) may be a reliable and a reproducible method to measure digital dermal thickness.In 70 patients with SSc, skin thickness was evaluated with US by 2 observers at 2 different sites on the second digit of the dominant limb to determine the interobserver variability. Patients and controls were examined twice by the first observer for intraobserver variability. Patients were divided into three subgroups according to the phase of the disease (oedematous, fibrotic or atrophic).At both examined areas, US showed a significant dermal thickening (p<0.001) in the whole group of patients with SSc. A low intraobserver and interobserver variability was found. A highly significant correlation between the global mRSS and the local dermal thickness at the two examined sites (p=0.032, p=0.021) was detected. Skin thickness was significantly higher in the oedematous than in the fibrotic group (p<0.001) and significantly higher in the fibrotic and the oedematous group (p<0.001) than in the atrophic group (p<0.002).US is a reliable tool giving reproducible results, and is able to detect digital dermal thickening in SSc.
A novel two-stage treatment of lentigo maligna using ablative laser therapy followed by imiquimod
Authors: K. de Vries, R. Rellum, J.M.W. Habets, E.P. Prens
Journal: British Journal of Dermatology (2012)

Funding sources: no external funding. Conflicts of interest: none declared. Madam, Lentigo maligna (LM) is a slowly growing premalignant skin cancer, typically arising in sun‐exposed skin in elderly individuals. The lifetime risk of LM progressing to LM melanoma varies from 2·2 to 4·7%.1 The first treatment of choice for LM is wide local excision with a margin of at least 5 mm, which leads to clearance rates of about 24–70% and recurrence rates of 7–20%.2 Staged surgical excision is associated with recurrence rates of 0–9·7%, with mean follow‐up periods of 4·7–96 months.2 In some patients, surgical treatment will inevitably lead to large skin defects and complex surgical reconstructions. Several alternative treatment modalities have been used, including topical imiquimod, laser therapy, radiation therapy and cryosurgery.2 Here we describe a novel treatment modality, whereby ablative laser therapy is followed by topical applications of imiquimod 5% cream for 6 weeks. From 2008 until 2011, 12 patients with histologically proven LM on the face who refused surgery were treated using a combination of ablative laser therapy and topical imiquimod 5% cream. The entire epidermis and the superficial papillary dermis of the LM lesion was vaporized after repeated passes using an Er : YAG laser. The endpoints of laser treatment were complete pigment clearance and the occurrence of punctuate bleeding. A margin of at least 2 cm of adjacent skin was also ablated. Patients started imiquimod application on the treated area the next day and continued once daily for 5 consecutive days per week, for a total of 6 weeks. The occurrence of an inflammatory reaction was assessed by two clinicians. The follow‐up for clinical evaluation (by W.H. or K.V. and E.P.) and signs of recurrence consisted of visits at 1, 3 and 6 weeks after laser treatment, and every 6 months thereafter. Dermoscopy was not performed. Patient characteristics are shown in Table 1.
Protein Expression Profiling in Esophageal Adenocarcinoma Patients Indicates Association of Heat-Shock Protein 27 Expression and Chemotherapy Response
Authors: Rupert Langer, Katja Ott, Katja Specht, Karen Becker, Florian Lordick, Maria Burian, Ken Herrmann, Andre Schrattenholz, Michael A. Cahill, Markus Schwaiger, Heinz Hofler, Hans-Jurgen Wester
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To identify pretherapeutic predictive biomarkers in tumor biopsies of patients with locally advanced esophageal adenocarcinomas treated with neoadjuvant chemotherapy, we used an explorative proteomic approach to correlate pretherapeutic protein expression profiles with tumor response to neoadjuvant chemotherapy. Experimental Design: Thirty-four patients with locally advanced esophageal adenocarcinomas who received neoadjuvant platin/5-fluorouracil–based chemotherapy before surgical resection were enrolled in this study. Response to chemotherapy was determined (a) by the amount of decline of [18F]fluorodeoxyglucose tumor uptake 2 weeks after the start of chemotherapy measured by positron emission tomography and (b) by histopathologic evaluation of tumor regression after surgical resection. Explorative quantitative and qualitative protein expression analysis was done through a quantitative differential protein expression analysis that used dual-isotope radioactive labeling of protein extracts. Selected identified biomarkers were validated by immunohistochemistry and quantitative real time reverse transcription-PCR. Results: Proteomic analysis revealed four cellular stress response–associated proteins [heat-shock protein (HSP) 27, HSP60, glucose-regulated protein (GRP) 94, GRP78] and a number of cytoskeletal proteins whose pretherapeutic abundance was significantly different (P &amp;lt; 0.001) between responders and nonresponders. Immunohistochemistry and gene expression analysis confirmed these data, showing a significant association between low HSP27 expression and nonresponse to neoadjuvant chemotherapy (P = 0.049 and P = 0.032, respectively). Conclusions: Albeit preliminary, our encouraging data suggest that protein expression profiling may distinguish cancers with a different response to chemotherapy. Our results suggest that response to chemotherapy may be related to a different activation of stress response and inflammatory biology in general. Moreover, the potential of HSPs and GRPs as biomarkers of chemotherapy response warrants further validation.
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers
Authors: Curtis R. Pickering, Jiexin Zhang, Suk Young Yoo, Linnea Bengtsson, Shhyam Moorthy, David M. Neskey, Mei Zhao, Marcus V. Ortega Alves, Kyle Chang, Jennifer Drummond, Elsa Cortez, Tong-xin Xie, Di Zhang, Woonbok Chung, Jean-Pierre J. Issa, Patrick A. Zweidler-McKay, Xifeng Wu, Adel K. El-Naggar, John N. Weinstein, Jing Wang, Donna M. Muzny, Richard A. Gibbs, David A. Wheeler, Jeffrey N. Myers, Mitchell J. Frederick
Journal: Cancer Discovery (2013)

The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.
Liberal Democrats end their opposition to health reforms
Authors: A. O'Dowd
Journal: BMJ (2011)

Some Liberal Democrat peers seem to have dropped their opposition to the government’s health reforms in the controversial Health and Social Care Bill after a concession from the government.

Doctors’ representatives and experts, however, have reiterated several concerns with the changes and have proposed amendments to the bill, which is currently at committee stage in the House of Lords on its way to becoming law next year.

A letter signed by 32 Liberal Democrat peers and published in the Guardian newspaper on 25 October (www.guardian.co.uk/society/2011/oct/25/libdems-draw-line-on-nhs) calls for certainty over the NHS’s future.

The Liberal Democrat peer Shirley Williams had previously raised concerns that the bill’s clause 1 concerning the health secretary’s role was ambiguous and could be taken to mean that he was no longer legally and constitutionally …
StandApp: stand up, stay healthy!
Authors: Richard Weiler
Journal: British Journal of Sports Medicine (2015)

Health

Apple (iOS 6.0 or later); also available for mass business purchase (price varies depending on user numbers) on desktop with Windows XP, 7, 8.

Free; StandApp Pro available for £0.79 without advertisements.

The initial welcome pages run through a simple brief education summary explaining key health benefits of standing compared to sitting. StandApp enables the user to set alarm reminders or regular interval alarms to interrupt time spent sitting down, with reminders to stand. There are video demonstrations of about 30 examples of simple desk-based stretches and exercises, which can be followed during 5 min standing breaks, as seen in figure 1. …
Baseline Neuropsychiatric Symptoms and the Risk of Incident Mild Cognitive Impairment: A Population-Based Study
Authors: Yonas E. Geda, Rosebud O. Roberts, Michelle M. Mielke, David S. Knopman, Teresa J.H. Christianson, Vernon S. Pankratz, Bradley F. Boeve, Ondřej Sochor, Eric G. Tangalos, Ronald C. Petersen, Walter A. Rocca
Journal: American Journal of Psychiatry (2014)

The authors conducted a prospective cohort study to estimate the risk of incident mild cognitive impairment in cognitively normal elderly (aged ≥70 years) individuals with or without neuropsychiatric symptoms at baseline. The research was conducted in the setting of the population-based Mayo Clinic Study of Aging.A classification of normal cognitive aging, mild cognitive impairment, and dementia was adjudicated by an expert consensus panel based on published criteria. Hazard ratios and 95% confidence intervals were computed using Cox proportional hazards model, with age as a time scale. Baseline Neuropsychiatric Inventory Questionnaire data were available for 1,587 cognitively normal persons who underwent at least one follow-up visit.The cohort was followed to incident mild cognitive impairment (N=365) or censoring variables (N=179) for a median of 5 years. Agitation (hazard ratio=3.06, 95% CI=1.89-4.93), apathy (hazard ratio=2.26, 95% CI=1.49-3.41), anxiety (hazard ratio=1.87, 95% CI=1.28-2.73), irritability (hazard ratio=1.84, 95% CI=1.31-2.58), and depression (hazard ratio=1.63, 95% CI=1.23-2.16), observed initially, increased risk for later mild cognitive impairment. Delusion and hallucination did not. A secondary analysis, limited in significance by the small number of study participants, showed that euphoria, disinhibition, and nighttime behaviors were significant predictors of nonamnestic mild cognitive impairment but not amnestic mild cognitive impairment. By contrast, depression predicted amnestic mild cognitive impairment (hazard ratio=1.74, 95% CI=1.22-2.47) but not nonamnestic mild cognitive impairment.An increased incidence of mild cognitive impairment was observed in community-dwelling elderly adults who had nonpsychotic psychiatric symptoms at baseline. These baseline psychiatric symptoms were of similar or greater magnitude as biomarkers (genetic and structural MRI) in increasing the risk of incident mild cognitive impairment.
Fluoridation of water supplies
Authors: H. T. Edmunds
Journal: BMJ (1967)

Hybridomas secreting monoclonal antibodies that reacted with the B6 radiation leukemia virus (RadLV)-induced leukemia B6RV2 were produced by fusion of BALB/c NS-1 myeloma cells with spleen cells from (BALB/c X B6)F1 mice immunized with B6RV2. By direct and absorption analyses with 28 B6 and BALB/c leukemias, the monoclonal antibodies NU7-4 and NU7-99 were shown to react only with B6RV2, indicating that they recognized an individually distinct antigen on B6RV2 that was identified previously with conventional (BALB/c X B6)F1 anti-B6RV2 serum. Another monoclonal antibody, NU1-132, showed relatively restricted reactivity with B6 RadLV leukemias. These three monoclonal antibodies all precipitated material of approximately 80,000 daltons, which is the same size as that precipitated by anti-xenotropic MuLV gp70 serum. Sequential immunoprecipitation analysis revealed that the molecules precipitated by NU7-4 were not removed by pretreatment of NU7-99 or NU1-132 and that the molecules precipitated by NU7-99 were not removed by NU7-4 or NU1-132. The molecules precipitated by NU1-132 were partially removed by pretreatment with NU7-4, but not with NU7-99. The molecules precipitated by these three monoclonal antibodies were removed by pretreatment with anti-xenotropic gp70. These results suggested heterogeneity of the xenotropic MuLV gp70-related molecules expressed on B6RV2 and a possible relation between serologically defined unique tumor antigens and gp70-related molecules.
Pathologic Complete Response and Survival Advantage in Esophageal Cancer: Old News
Authors: Michael J. Kraut
Journal: Journal of Clinical Oncology (2004)

osteogenic sarcoma: The Memorial Sloan-Kettering experience. J Clin Oncol 10:5-15, 1992 9. Delepine N, Delepine G, Desbois JC: A monocentric therapy study: An approach to optimize the results of the treatment of osteosarcoma by protocols based upon HDMTX, associated with systematic conservative surgery, in Humphrey GB (ed): Osteosarcoma in Adolescent and Young Adults. Boston, MA, Kluwer Academic Publishers, 1993
Genetic issues in “the sociobiology of sociopathy”
Authors: Stephen C. Maxson
Journal: Behavioral and Brain Sciences (1995)

Abstract A consideration of the genetics of sociopathy suggests the following. The author's Evolutionary Stable Strategy (ESS) types 2 to 4 are more likely than types 1 and 5 in crimes of violence, and there may not be an ESS for crimes of property or for sociopathy. Correlations between sociopathy and crimes of property are also more likely due to environmental than to genetic variants, and correlations between sociopathy and crimes of property are due more to environmental than genetic variants.
Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications
Authors: Lisa Hartling, Ahmed M. Abou-Setta, Serdar Dursun, Shima S. Mousavi, Dion Pasichnyk, Amanda S. Newton
Journal: Annals of Internal Medicine (2012)

Background: Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. Purpose: To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality, tardive dyskinesia, and a major metabolic syndrome. Data Sources: English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature. Study Selection: Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events. Data Extraction: Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach. Data Synthesis: Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole, increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus. Limitations: All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability. Conclusion: Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient. Primary Funding Source: Agency for Healthcare Research and Quality.
Targeting Dendritic Cells with Antigen-Containing Liposomes
Authors: Christina L. van Broekhoven, Christopher R. Parish, Caroline Demangel, Warwick J. Britton, Joseph G. Altin
Journal: Cancer Research (2004)

Dendritic cells (DCs) are potent stimulators of immunity, and DCs pulsed with tumor antigen ex vivo have applications in tumor immunotherapy. However, DCs are a small population of cells, and their isolation and pulsing with antigen can be impractical. Here we show that a crude preparation of plasma membrane vesicles (PMV) from the highly metastatic murine melanoma (B16-OVA) and a surrogate tumor antigen (OVA) can be targeted directly to DCs in vivo to elicit functional effects. A novel metal-chelating lipid, 3(nitrilotriacetic acid)-ditetradecylamine, was incorporated into B16-OVA-derived PMV, allowing recombinant hexahistidine-tagged forms of single chain antibody fragments to the DC surface molecules CD11c and DEC-205, to be conveniently "engrafted" onto the vesicle surface by metal-chelating linkage. The modified PMV, or similarly engrafted synthetic stealth liposomes containing OVA or OVA peptide antigen, were found to target DCs in vitro and in vivo, in experiments using flow cytometry and fluorescence confocal microscopy. When used as vaccines in syngeneic mice, the preparations stimulated strong B16-OVA-specific CTL responses in splenic T cells and a marked protection against tumor growth. Protection was dependent on the simultaneous delivery of both antigen and a DC maturation or "danger signal" signal (IFN-gamma or lipopolysaccharide). Administration of the DC-targeting vaccine to mice challenged with B16-OVA cells induced a dramatic immunotherapeutic effect and prolonged disease-free survival. The results show that the targeting of antigen to DCs in this way is highly effective at inducing immunity and protection against the tumor, with protection being at least partially dependent on the eosinophil chemokine eotaxin.
Heterologous T cell immunity in severe hepatitis C virus infection
Authors: Simona Urbani, Barbara Amadei, Paola Fisicaro, Massimo Pilli, Gabriele Missale, Antonio Bertoletti, Carlo Ferrari
Journal: The Journal of Experimental Medicine (2005)

Hepatitis C virus (HCV) can cause liver disease of variable severity. Expansion of preexisting memory CD8 T cells by cross-reactivity with a new heterologous virus infection has been shown in mice to shape the repertoire of the primary response and to influence virus-related immunopathology (Selin, L.K. 2004. Immunity. 20:5–16). To determine whether this mechanism can influence the course of HCV infection, we analyzed the features of the HCV-specific CD8 T cell response in eight patients with acute HCV infection, two of whom had a particularly severe illness. Patients with severe hepatitis, but not those with mild disease, showed an extremely vigorous CD8 T cell response narrowly focused on a single epitope (NS3 1073–1081), which cross-reacted with an influenza neuraminidase sequence. Our results suggest that CD8 T cell cross-reactivity influences the severity of the HCV-associated liver pathology and depicts a model of disease induction that may apply to different viral infections.
Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma
Authors: F. Morschhauser, P. Marlton, U. Vitolo, O. Lindén, J.F. Seymour, M. Crump, B. Coiffier, R. Foà, E. Wassner, H.-U. Burger, B. Brennan, M. Mendila
Journal: Annals of Oncology (2010)
DNA Vaccination Controls Her-2+ Tumors that Are Refractory to Targeted Therapies
Authors: Paula J. Whittington, Marie P. Piechocki, Henry H. Heng, Jennifer B. Jacob, Richard F. Jones, Jessica B. Back, Wei-Zen Wei
Journal: Cancer Research (2008)

Abstract Her-2/neu+ tumor cells refractory to antibody or receptor tyrosine kinase inhibitors are emerging in treated patients. To investigate if drug resistant tumors can be controlled by active vaccination, gefitinib and antibody sensitivity of four neu+ BALB/c mouse mammary tumor lines were compared. Significant differences in cell proliferation and Akt phosphorylation were observed. Treatment-induced drug resistance was associated with increased chromosomal aberrations as shown by spectral karyotyping analysis, suggesting changes beyond neu signaling pathways. When mice were immunized with pneuTM encoding the extracellular and transmembrane domains of neu, antibody and T-cell responses were induced, and both drug-sensitive and drug-resistant tumor cells were rejected. In T-cell–depleted mice, drug-sensitive tumors were still rejected by vaccination, but drug-refractory tumors survived in some mice, indicating their resistance to anti-neu antibodies. To further test if T cells alone can mediate tumor rejection, mice were immunized with pcytneu encoding full-length cytoplasmic neu that is rapidly degraded by the proteasome to activate CD8 T cells without inducing antibody response. All test tumors were rejected in pcytneu-immunized mice, regardless of their sensitivity to gefitinib or antibody. Therefore, cytotoxic T lymphocytes activated by the complete repertoire of neu epitopes were effective against all test tumors. These results warrant Her-2 vaccination whether tumor cells are sensitive or resistant to Her-2–targeted drugs or antibody therapy. [Cancer Res 2008;68(18):7502–11]
Effect of Hypertonic Saline on the Pulmonary and Systemic Pressures
Authors: M. ELIAKIM, S. Z. ROSENBERG, K. BRAUN
Journal: Circulation Research (1958)

The intravenous injection of 20 per cent saline in anesthetized closed chest dogs causes a rise in pulmonary venous, pulmonary arterial, right ventricular and peripheral venous pressures. Left atrial pressure does not change or falls, and systemic arterial pressure decreases very markedly. These changes are shown to result from spasm at the pulmonary vein--left atrial junction. Stimulation of chemoreceptors in this region is assumed to be the cause of the spasm.