tbuckley/cabot-search huggingface dataset:
Former India medical council president is cleared of six of seven corruption charges
Authors: Priyanka Pulla
Journal: BMJ (2015)

Ketan Desai, the former president of the Medical Council of India who was charged by India’s Central Bureau of Investigation with several cases of corruption in 2010, has been exonerated in all but one of the cases. 

On 21 September a Lucknow special court dropped charges that Desai, in collusion with other members of the council, had granted permission for Shri Ram Murti Smarak Institute of Medical Sciences in Bareilly, Uttar Pradesh, to admit students, even though the institute lacked the infrastructure and teaching staff required under the council’s rules.

In its ruling, the special Central Bureau of Investigation court in Lucknow said that there was no evidence that Desai had abused his office to favour the medical college or had received any benefits in return. The bureau had relied on several pieces of evidence to build its case against Desai. The first was a …
Phase 1b Dose-Escalation Study of Sonidegib (LDE225) in Combination with Ruxolitinib (INC424) in Patients with Myelofibrosis
Authors: Vikas Gupta, Steffen Koschmieder, Claire N. Harrison, Francisco Cervantes, Florian H Heidel, Mark Drummond, Jerome Rey, Eunju Hurh, Weichao Bao, Anita Rampersad, Stacey Kalambakas, Alessandro Maria Vannucchi
Journal: Blood (2014)
Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer.
Authors: M Martín, A Lluch, A Casado, P Santabárbara, E Adrover, J J Valverde, J A López-Martín, A Rodriguez-Lescure, P Azagra, J García-Conde
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was undertaken to assess the antitumor activity and tolerance of chronic oral etoposide (50 mg/m2/d for 21 days every 4 weeks) in metastatic breast cancer (MBC). PATIENTS AND METHODS Forty-three consecutive metastatic breast cancer patients with at least one site of measurable disease entered the study. All patients had received prior chemotherapy (adjuvant, three patients; adjuvant plus chemotherapy for metastases, 21; chemotherapy for metastases, 19). Twenty-two and 21 patients had also received prior hormonal and radiation therapy, respectively. RESULTS Thirty-five percent of patients (15 of 43; 95% confidence interval, 21% to 51%) had objective responses, according to an intention-to-treat analysis. Responses were seen in lymph nodes (six of 14), skin and soft tissues (eight of 16), lung (six of 14), lytic lesions of the bone (two of six), liver (four of 23), and peritoneum (one of one). The median duration of response was 7 months (range, 3+ to 12). The main toxic side effects were leukopenia (overall, 65% of patients; World Health Organization [WHO] grade 4, 21%), thrombocytopenia (21%; WHO grade 4, 5%) and anemia (51%; WHO grade 4, 5%). Nine patients (21%) required a 25% dose reduction because of myelosuppression, and one patient abandoned treatment because of gastrointestinal toxicity and severe asthenia. Ninety-one percent of patients developed alopecia, 39.5% had mucositis (WHO grade 3, 9.5%) and 60.5% had some degree of emesis (11.5% nausea, 46.5% transient vomiting, 2.5% intractable vomiting). No toxic deaths occurred. CONCLUSION Chronic oral etoposide appears to be an active and well-tolerated regimen in MBC patients previously exposed to chemotherapy. This schedule of etoposide administration warrants further studies, alone or in combination, in MBC.
Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative.
Authors: C H Pui, S C Raimondi, M L Hancock, G K Rivera, R C Ribeiro, H H Mahmoud, J T Sandlund, W M Crist, F G Behm
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the immunophenotypes, karyotypes, and clinical features, including treatment responses, of patients with childhood acute lymphoblastic leukemia (ALL) and either a t(1;19)(q23;p13) or a der(19)t(1;19)(q23;p13) translocation. PATIENTS AND METHODS The lymphoblasts of 45 patients with a balanced translocation, t(1;19) or its derivative form, der(19)t(1;19), were analyzed by cytogenetic and immunologic methods for differences that might suggest distinct subtypes of ALL. This cohort was treated in four consecutive clinical trials with a median overall follow-up duration of 7 years. RESULTS A pre-B immunophenotype was found in 10 cases with the balanced t(1;19) and 31 with the unbalanced der(19)t(1;19). The four remaining cases, each with a derivative t(1;19), were classified as early pre-B ALL. The characteristic surface antigen profile of the 41 pre-B cases was CD19+/CD10+/CD22+/CD34-/CD20+/-, whether the translocation was balanced or derivative. In contrast to the four early pre-B cases, which had hyperdiploid karyotypes (&gt; 50 chromosomes), the pre-B cases were primarily pseudodiploid. Comparison of presenting clinical and laboratory features, as well as event-free survival, failed to disclose any differences that would warrant separation of pre-B cases with a balanced or derivative translocation. However, neither subgroup responded to therapy as well as patients with early pre-B ALL, each of whom remains in complete remission for &gt; or = 3 years. CONCLUSION The t(1;19) and the der(19)t(1;19) identify a relatively homogeneous group of patients with pre-B ALL, who can be expected to respond similarly to intensive chemotherapy. The exceptional cases have an early pre-B phenotype with hyperdiploid karyotypes and appear to have favorable prognosis.
Preventing injuries from bar glasses
Authors: J Cole, M Plant, P Miller, M Plant, P Nichol
Journal: BMJ (1994)

EDITOR, - Jonathan Shepherd's editorial on preventing injuries from bar glasses highlights the importance of violence as a public health issue.1

Work in the south east of England to determine priorities in preventing accidents and reducing injuries that are consistent with the Health of the Nation strategy has provisionally identified assaults among young men (aged 15 to 34) as an area for further consideration.2

As a result, East Sussex Health Authority is currently conducting a retrospective study into the causes of injury among the 316 declared victims of assault who attended a local accident and emergency department in 1993. How many of these assaults involved injuries from beer glasses has yet to be determined. Initial correspondence with the local licensed victuallers association suggests, however, that publicans will be resistant to the voluntary introduction of tempered glassware regardless of the final extent …
Double-scope resection of a large duodenal polyp
Authors: Richard Knoop, Hans-Jürgen Richter-Schrag, Christine Walker, Robert Thimme, Andreas Fischer
Journal: Endoscopy (2015)

An 83-year-old man underwent right colectomy with ileostomy because of Ogilvie syndrome with perforation of the ascending colon. After 10 days, the patient, who had multiple co-morbidities, had a myocardial infarction without ST-segment elevation. For this reason, percutaneous coronary intervention with the application of bare metal stents was required, and he subsequently received the standard dosage of antiplatelet therapy with acetylsalicylic acid and clopidogrel.
P0772 : Daclatasvir plus sofosbuvir with or without ribavirin for the treatment of HCV in patients with severe liver disease: Interim results of a multicenter compassionate use program
Authors: T.M. Welzel, K. Herzer, P. Ferenci, J. Petersen, M. Gschwantler, M. Cornberg, T. Berg, U. Spengler, O. Weiland, M. Van der Valk, H. Klinker, J. Rockstroh, P. Ingiliz, M. Peck-Radosavljevic, M.J. Jimenez-Exposito, S. Zeuzem
Journal: Journal of Hepatology (2015)
Cancer metastases: challenges and opportunities
Authors: Xiangming Guan
Journal: Acta Pharmaceutica Sinica B (2015)

Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been significantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs (predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment (such as extracellular matrix structure, growth factors, chemokines, matrix metalloproteinases) plays a significant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.
Urinary Biomarkers for Diagnosis of Bladder Cancer
Authors: Roger Chou, John L. Gore, David Buckley, Rongwei Fu, Katie Gustafson, Jessica C. Griffin, Sara Grusing, Shelley Selph
Journal: Annals of Internal Medicine (2015)

Background: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. Purpose: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Data Sources: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22 (NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case–control studies were excluded. Data Extraction: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Data Synthesis: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. Limitation: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Conclusion: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284)
Abstract 9685: Microrna-126-Containing Endothelial Microparticles Reduce Neointimaformation and Vascular Smooth Muscle Cell Proliferation
Authors: Feilx Jansen, Tobias Stumpf, Georg Nickenig, Nikos Werner
Journal: Circulation (2014)

Itroduction:  Endothelial microparticles (EMP) have been shown to promote vascular regeneration by transferring functional microRNAs, but whether they influence VSMC biology is largely unknown.   Hypothesis:  EMP influence neointima formation in a model of acute vascular injury in vivo and VSMC proliferation and migration in vitro.   Methods and Results:  After wire injury of the carotid artery, mice treated with EMP showed a significantly reduced neointima formation (0.63±0.03 vs. 0.47±0.04,p   Conclusions:  EMP reduce neointima formation in a model of acute arterial injury in vivo and decrease proliferation and migration of vascular smooth muscle cells in vitro. The transfer of mir-126 by EMP and subsequent inhibition of LRP6 expression in VSMCs might be a possible pathway.
Subgross Pathology of the Human Breast: Method and Initial Observations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ronald G. Marcum, S. R. Wellings
Journal: JNCI Journal of the National Cancer Institute (1969)

A method is described for study of the subgross anatomy of entire human breasts obtained at surgery or autopsy. The tissue is serially sectioned at 1–2 mm, defatted in acetone, hydrated, stained 3 hours in hematoxylin at pH 1, dehydrated, cleared in toluene, and stored in sealed plastic bags containing methyl salicylate. Lesions may be studied at low magnifications and photographed without being taken from the bags. Subsequently, the bags can be opened and selected parts of the specimen removed for the preparation of ordinary microscopic slides. Thus light microscopy at the histologic level can be correlated with subgross anatomy. The method offers the advantages of convenience, simplicity, and reliability. It permits quantitative and statistical approaches to the study of focal dysplastic and anaplastic lesions in the human mammary gland.
Abstract P278: Effects of the Optimal Macro-Nutrient Intake to Prevent Heart Disease (OmniHeart) diets on urinary excretion profiles
Authors: Ruey Leng Loo, Xin Zou, Lawrence Appel, Jeremy K Nicolson, Elaine Holmes
Journal: Circulation (2014)

Background: OmniHeart diets are diets rich in fruit, vegetables, and low-fat diary food with varying amount of carbohydrate, protein and unsaturated fat. These diets have been shown to reduce blood pressure, low-density lipoprotein cholesterol and coronary heart disease risk. However, the biological mechanism for this is unclear. Objective: The aim of this study is to evaluate the effects of OmniHeart diets on the urinary profiles by proton nuclear magnetic resonance ( 1 H NMR). Methods: 158 men and women, aged 30 years and older, with prehypertension or stage 1 hypertension, each consumed three different OmniHeart diets for six weeks: a carbohydrate-rich diet (Carb, similar to the Dietary Approaches to Stop Hypertension, DASH diet); a protein-rich diet with protein predominantly from plant sources (Prot); and an unsaturated fat-rich diet mainly using monounsaturated fat (Unsat). All participants provided urine specimens at baseline (on a typical ‘American’ diet), and at the end of each dietary intervention. Spectra were acquired using a standard one dimensional experiment. Pairwise multilevel orthogonal partial least squares-discriminant analysis (OPLS-DA) comparison were made between baseline and each dietary intervention. Results: All three multilevel OPLS-DA models showed clear separation between baseline and different OmniHeart diets, with model predictability (Q 2 Yhat) between 75 - 85 %. The urine 1 H NMR spectra for OmniHeart diets were characterised by the higher concentrations of several metabolites of both exogenous and endogenous origin, as well as those derived from gut microbiota. Core molecules common to all three OmniHeart diets were also observed. The baseline urine spectra were characterised by the higher concentrations of molecules present in the aliphatic regions of the urine 1 H NMR spectra. Conclusion: NMR-based metabolic phenotyping approach provides an objective method for assessing the impact of different healthy diets in human population. It has the potential to delineate the complexities of dietary effect on human health. Future work aims to determine the identity of these discriminating molecules and to possibly un-cover the biological mechanisms of how these molecules may contribute the reduction of cardiovascular risk.
High-throughput detection of alternative splicing in patients with non-small cell lung cancer treated by bevacizumab/erlotinib
Authors: Florent Baty, Martin Brutsche
Journal: European Respiratory Journal (2014)

Introduction  Alternative splicing is an important component of tumorigenesis. Recent advent of exon array technology enables the detection of alternative splicing at a genome-wide scale. Few analysis tools of high-throughput alternative splicing are currently available. We propose a novel statistical approach for the detection of splicing changes in exon array data. Using this methodology, we investigated the genome-wide alteration of alternative splicing in NSCLC patients treated by bevacizumab/erlotinib.  Methods  We used restricted constrained correspondence analysis (RCCA) to explore the exonic variations with respect to disease phenotypes. We applied RCCA on oncological data investigating the response to targeted therapy on late stage non-squamous NSCLC. Exonic expression levels were measured on bronchospic biopsies from 42 patients treated by bevacizumab/erlotinib using Affymetrix GeneChip Human Exon 1.0 ST Array. Patients were categorized into responders/non-responders according to their response to treatment.  Results  Splicing candidates reveal a series of genes related to carcinogenesis, cell adhesion, tumor aggressiveness, apoptosis, proliferation and differentiation, as well as tumor growth or tumor suppression, with indication of known alternative splicing in a majority of genes. Diagnostic markers of metastasis and micrometastasis were also found.  Conclusion  RCCA facilitates the identification of biologically relevant alternative splicing events in high-throughput exon array data. The flexibility of this approach makes it ideal as a screening procedure for identification of splicing sites candidates and group-specific alternative splicing events.
Elicitability of defensive reflexes within the breathing cycle
Authors: Silvia Varechova, Bruno Demoulin, Mathias Poussel, Cyril Schweitzer, Bruno Chenuel, Anne-Laure Leblanc, Francois Marchal
Journal: European Respiratory Journal (2011)

Background:  Both the cough (CR) and the expiration reflex (ER) are usually elicited within prolonged (more than 10 s) mechanical stimulation. The use of a discrete mechanical stimulus (150 ms) has shown that the type of response is strongly dependent on the phase of the breathing cycle. CR is favoured in inspiration (I) and ER in expiration (E). The observation suggests that CR and ER exhibit different regulatory mechanisms, but it still remains unclear which mechanisms control the expression of these reflexes.  The aim of the study was to assess the elicitability of CR and ER in relation to the timing of stimulation within breathing.   Methods:  313 mechanical stimulations of the trachea were performed in 14 rabbits using stimuli lasting 50 to 600 ms. CR and ER were identified from airflow and tidal volume. The timing of the stimulus was defined within TI and TE arbitrarily divided into 4 equivalent epochs (TI1 to TI4 and TE1 to TE4) and expressed as percentage of TI and TE of the reference breath.   Results:  CR incidence during TI increased from 43% in TI1 to 56% in TI4. CR was almost absent in TE1 (4%) and whenever observed, always preceded by ER. In TE2-4, CR incidence increased, e.g., 50% in T3, to a nadir of 75% at TE4, i.e. the transition from TE to TI. On the contrary, incidence of ER increased throughout inspiration (from 15% in TI1 to 50% in TI4), and further to 54% to in TE1. The incidence then decreased gradually from 53% in TE2 to 19% in TE4.   Conclusions:  Elicitability of CR and ER exhibit a completely different pattern within each phase of breathing suggesting implication of distinct control mechanisms in their regulation and/or different impact of inputs from lung afferents in tuning of the CR and ER.
Real-World Analysis Of Celgene Global Drug Safety (GDS) Database: Early Permanent Discontinuation (D/C) Of Lenalidomide (LEN) In Patients (Pts) With Myelodysplastic Syndromes (MDS) Due To Nonserious (NS) Rash
Authors: Lilia Weiss, Dianna Gary, Arlene S. Swern, John Freeman, Mary M. Sugrue
Journal: Blood (2013)
Pneumatic displacement of submacular hemorrhage11The following letter addresses an article that appeared in the October 1999 issue of the Journal: Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. (Ophthalmology 1999;106:1900–6)
Authors: Edward Averbukh, Robert G Devenyi, Wai-Ching Lam, Alan R Berger
Journal: Ophthalmology (2000)
Alternative splicing of <i>Krüppel-like factor 6 (KLF6)</i> enriched in human androgen-deprived prostate cancer (PC).
Authors: XiaoMei Liu, Alejandro Gomez-Pinillos, Charisse Loder, Enrique Carrillo-de Santa Pau, Rui Fang Quiao, Pamela D Unger, Ralf Kurek, Carole Oddoux, Jonathan Melamed, Robert E Gallagher, John P Mandeli, Anna C. Ferrari
Journal: Journal of Clinical Oncology (2012)

e15191 Background: Inactivation of KLF6 by mutations and alternative splicing has been implicated in PC. However, there are significant discrepancies among human PC studies concerning the prevalence and significance of KLF6 mutations, and the prevalence of splice variants (SVs) has not been established. The objective of this study was to assess the prevalence and role of KLF6 splicing in human PC progression. Methods: Human specimens were obtained from the tissue banks of three institutions. Representative epithelium of 74 frozen PC specimens [25 primary hormone-naïve (HN) PCs, 21 primary hormone-deprived (HD) PCs, 6 castrate-resistant metastases] and 22 normal prostates (NPs) were microdissected. KLF6 cDNA was amplified by PCR, cloned and sequenced in both forward and reverse directions and compared to the KLF6 GenBank sequence. The transcriptional activity of KLF6 SVs was evaluated in co-transfection assays with a p21-reporter, and their effect on LNCaP cell growth was determined by MTT assays. Results: Sixteen different SVs were identified: 13 were novel; 14 affected the DNA binding domain (DBD) and were transcriptionally inactive. The incidence of SVs was increased in PC versus NP (75% vs 45%; p=0.01) and in HD-PC versus HN-PC (90% vs 64%; p=0.04) HD-PC were significantly enriched in SVs lacking the DBD. Forced expression of dysfunctional KLF6 SVs increased growth of LNCaP cells in androgen-depleted media. Conclusions: KLF6 SVs lacking p21-reporter transactivation activity occur in NP epithelium but are markedly increased in incidence, variety and level of expression in PC tissues that survive androgen-deprivation. This enrichment may enable resistance to hormone therapy and a proliferative advantage under castrate conditions.