tbuckley/cabot-search huggingface dataset:
Egyptian doctors vote for free hospital care in police assault protest
Authors: Owen Dyer
Journal: BMJ (2016)

Egypt's doctors, angered by what they said was the growing problem of police violence in hospitals, have planned more demonstrations this week after more than 4000 gathered on Friday to demand police accountability and the health minister's resignation. They voted to start a campaign of strikes across Egypt if their demands were not met in two weeks.

Doctors filled all three floors, the roof, and the streets outside the Cairo headquarters of their union, the Egyptian Medical Syndicate. Many were carrying placards and others had their hands bound with stethoscopes.

The “unprecedented” turnout marked “a turning point in our union’s history,” the syndicate's chairman, Hussein Khairy, said. The protest was in defiance of the military backed government’s ban on public demonstrations, but there was no police response.

The doctors' protest was triggered by the 28 January …
Five-year follow-up of a prospective randomised multi-centre trial of weekly chemotherapy (CAPOMEt) versus cyclical chemotherapy (CHOP-Mtx) in the treatment of aggressive non-Hodgkin’s lymphoma
Authors: N.P. Bailey, N.S.A. Stuart, E.M. Bessell, J.A. Child, D. Norfolk, J. Fletcher, R.J. Grieve, A.V. Simmons, D.L. Barnard, A. Jack, J. Farish, J. Dunn, C.M. Woodroffe, C. Stack, M.H. Cullen
Journal: Annals of Oncology (1998)
Uridine triacetate for lethal 5-FU toxicity due to dihydropyrimidine dehydrogenase (DPD) deficiency.
Authors: R. von Borstel, J. D. O'Neil, J. A. Saydoff, M. K. Bamat
Journal: Journal of Clinical Oncology (2010)

e13505 Background: The enzyme dihydropyrimidine dehydrogenase (DPD) catalyzes the first step in degradation of 5-fluorouracil (5FU). Patients with complete or partial DPD deficiency (about 0.1% and 3% of the population, respectively) can experience severe or lethal toxicities after receiving standard doses of 5FU, and impaired clearance may underlie a large fraction of the ∼1,300 deaths per year due to 5FU toxicity in the US. Orally-administered uridine triacetate (vistonuridine) prevents or diminishes toxicities when administered after 5FU overexposure, and has been used successfully as an antidote in more than 28 patients to date who had received accidental overdoses of 5FU. Because DPD deficiency may alter 5FU clearance kinetics (versus 5FU overdoses in the setting of normal DPD activity), studies were conducted on reversal of 5FU toxicity in mice pretreated with the potent DPD inhibitor ethynyluracil (eniluracil; EU) to model DPD deficiency. Methods: Balb/C mice received 2 mg/kg EU i.p., followed by 100 mg/kg 5FU (weekly bolus MTD in mice). Groups of 10 mice each then received either vehicle or oral uridine triacetate (2,000 mg/kg t.id. × 5) beginning at a range of times after 5FU. Survival was monitored. Results: 100 mg/kg 5FU was lethal in mice pretreated with EU. Uridine triacetate administration beginning within 24 hours after EU + 5FU resulted in survival of all the mice in the treatment groups. Fewer mice survived if treated with uridine triacetate at later time points after EU plus 5FU. Conclusions: Timely treatment with uridine triacetate reduced 5FU toxicity and mortality in DPD-inhibited mice. Its benefit has previously been demonstrated in patients (and mice) overdosed with 5FU. Therefore, DPD-deficient patients who have received 5FU should also benefit from treatment with uridine triacetate if the deficiency is identified soon enough after 5FU dosing. Therapeutic monitoring of 5FU during or after infusions could permit rapid detection of 5FU overexposure due to DPD-deficiency, enabling the use of uridine triacetate as an antidote in DPD-deficient patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wellstat Therapeutics Corporation
HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir
Authors: Harel Dahari, Laetitia Canini, Frederik Graw, Susan L. Uprichard, Evaldo S.A. Araújo, Guillaume Penaranda, Emilie Coquet, Laurent Chiche, Aurelie Riso, Christophe Renou, Marc Bourliere, Scott J. Cotler, Philippe Halfon
Journal: Journal of Hepatology (2016)
Epidemiology of rotavirus in Andaman and Nicobar Islands, India – Predominance of G1 and emergence of G12 strains
Authors: Rajesh Reesu, N. Muruganandam, Itta Krishna Chaaithanya, Anwesh Maile, Attayur Purushottaman Sugunan, A.N. Shriram, Ashok Kumar Biswas, Ageshwar Prasad Bharadwaj, Munni Singhania, Brij Gopal Lall, Paluru Vijayachari
Journal: Journal of Infection (2016)
Transcriptional upregulation of microtubule-associated protein 2 is involved in the protein kinase A-induced decrease in the invasiveness of glioma cells
Authors: Yuxi Zhou, Sihan Wu, Chaofeng Liang, Yuan Lin, Yan Zou, Kai Li, Bingzheng Lu, Minfeng Shu, Yijun Huang, Wenbo Zhu, Zhuang Kang, Dong Xu, Jun Hu, Guangmei Yan
Journal: Neuro-Oncology (2015)

Malignant glioma is the most lethal primary tumor of the central nervous system, with notable cell invasion causing significant recurrence. Suppression of glioma invasion is very important for improving clinical outcomes. Drugs that directly disrupt the cytoskeleton have been developed for this purpose; however, drug resistance and unsatisfactory selectivity have limited their clinical use. Previously, we reported that protein kinase A (PKA, also known as cyclic-AMP dependent protein kinase) activation induced the differentiation of glioma cells.We used several small molecular inhibitors and RNA interference, combined with wound healing assays, Matrigel transwell assay, and microscopic observation, to determine whether activation of the PKA pathway could inhibit the invasion of human glioma cells.Activation of PKA decreased the invasion of glioma cells. The mechanism operated via transcriptional upregulation of microtubule-associated protein 2 (MAP2), which was activated by the PKA pathway and led to ossification of microtubule dynamics via polymerization of tubulin. This resulted in morphological changes and a reduction in glioma cell invasion. Furthermore, chromosome immunoprecipitation and quantitative real-time polymerase chain reaction showed that signal transducer and activator of transcription 3 (STAT3) is involved in the transcriptional upregulation of MAP2.Our findings suggested that PKA may represent a potential target for anti-invasion glioma therapy and that the downstream modulators (eg, STAT3/MAP2) partially mediate the effects of PKA.
Phase II trial of oral suberoylanilide hydroxamic acid (SAHA) for cutaneous T-cell lymphoma (CTCL) unresponsive to conventional therapy
Authors: M. Duvic, R. Talpur, C. Zhang, A. Goy, V. Richon, S. R. Frankel
Journal: Journal of Clinical Oncology (2005)

6571 Background: Epigenetic modulation of genes controlling apoptosis and differentiation is an attractive strategy for targeted cancer therapies. Suberoylanilide hydroxamic acid (SAHA), an oral inhibitor of class I and II histone deacetylases, induces apoptosis of malignant cutaneous T-cell lymphoma (CTCL) cell lines and Sezary Syndrome (SS) patients’ cells at clinically achievable doses. Methods: Thirty-seven advanced, refractory CTCL patients were treated with three oral dosing regimens of SAHA in a Phase II opened label trial. Results: Ten of 37 (27%) of patients, including 3 with large cell transformed tumors and 7 with SS, achieved a PR as evaluated by a physician global assessment score (> 50% reduction in disease burden). Lymphadenopathy decreased by more than 50% in 15 of 26 pts (58%), and pruritus in 21 of 31 pts (68%). Thirteen patients discontinued for progressive disease, and ten withdrew for adverse events of fatigue, anemia, rash, cutaneous neuropathy, leukopenia, weight loss (1 each), prior DVT with pulmonary embolism (2 pts), or thrombocytopenia (3 pts). The most common toxicities irrespective of grade were fatigue (27) or GI symptoms including diarrhea (21), nausea (19), dysguesia (17), dry mouth (14), and decreased appetite (13). Thrombocytopenia occurred in 21 of 37 pts (57%) at Gr 1 = 13, Gr 2 = 1, Gr 3 =3 and Gr 4 = 4 pts. Conclusions: Oral SAHA produced clinically meaningful partial responses (skin, nodes and blood) in 10 of 37 advanced, heavily pre-treated CTCL patients associated with decreased pruritus. The dosing regimen of 400 mg daily is undergoing confirmatory study in a phase IIb trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Aton
Evaluation of nausea control with NEPA, a novel oral combination antiemetic.
Authors: Snezana Bosnjak, Lee Steven Schwartzberg, Giada Rizzi, Maria Elisa Borroni
Journal: Journal of Clinical Oncology (2014)

169 Background: The introduction of NK 1 receptor antagonists (RAs) improved the control of chemotherapy-induced nausea and vomiting. However, prevention of nausea, particularly in the delayed phase remains suboptimal, with no consistent superiority seen with the addition of aprepitant over 5-HT 3 RAs + dexamethasone (DEX). NEPA, a fixed-dose oral combination of the new NK 1 RA, netupitant (NETU 300 mg) plus palonosetron (PALO 0.50 mg) targets two main antiemetic pathways with a convenient single dose. NEPA has shown superior complete response rates (no vomiting and no rescue use) compared with PALO in pivotal trials. This analysis summarizes the nausea control seen with NEPA in all 3 pivotal trials in the clinical development program. Methods: Patients in 3 randomized, double-blind trials received a single dose of NEPA + DEX prior to a variety of either highly emetogenic (HEC) (Studies 1 and 3) or moderately emetogenic (MEC) (Studies 2 and 3) chemotherapeutic agents. Patients receiving HEC also received additional DEX on Days 2–4. Nausea was measured daily with a 100 mm visual analog scale (VAS). The proportion of patients with no significant nausea (VAS &lt;25 mm) were summarized (Table). Results: In Studies 1 and 2, NEPA was significantly more effective in controlling delayed and overall nausea compared with PALO (Table). The greatest nausea control with NEPA was seen in the non-AC MEC and HEC settings. Conclusions: This summary suggests that NEPA + DEX improves control of nausea during the delayed and overall periods following chemotherapy. High levels of nausea control were seen and were most noteworthy in patients receiving HEC or non-AC MEC. Clinical trial information: NCT01339260; NCT01376297. [Table: see text]
IP-10 measurement using a point of care test for the diagnosis of active tuberculosis
Authors: Berit Lange, Martina Vavra, Winfried Kern, Wagner Dirk
Journal: European Respiratory Journal (2011)

Introduction:  Measurement of IP-10 released by whole blood stimulation with tuberculosis (TB) specific antigens has recently been proposed as a new tool for the diagnosis of tuberculosis (TB) with a sensitivity (SE) similar to that of the Quantiferon TB in tube-assay (QFT, Cellestis). More data is needed on the detection as well as indeterminate rates in IP-10-dependent diagnosis for active TB.   Methods:  IP-10 was measured in the supernatants of QFT tests in 81 patients with known TB status (active TB at the time of sampling in 25 patients). QFT results were indeterminate in 41 patients, negative in 13, and positive in 27 of the 81 patients. IP-10 was measured by using a multiplex assay (MPA, Biorad) (50 patients only), or by using a semiquantitative lateral flow immunoassay (LFI, Milenia Biotec). Samples with a mitogen control ≥500 pg of IP-10 per mL were considered determinate. The cut-off for IP-10 positivity in determinate tests was 455 pg/mL both MPA and LFI.   Results:  Indeterminate results were reduced by 56% (18/41) using IP-10 LFI in comparison with QFT. 5% (2/40) determinate QFT results turned indeterminate in IP-10 LFI. Pearson correlation for IP-10 measurements by MPA and LFI was 0.53 (95%CI 0.3-0.7). The SE in patients with active TB was 56% for QFT (14/25, CI 0,35-0.76), 70% for IP-10 MPA (19/25; CI 0.55-0.9) and 63% for IP-10 LFI (15/24; CI 0.4-0.81).   Conclusion:  IP-10 measured by LFI and IFN-γ measured by QFT had comparable detection and indeterminate rates. A combination of IFN-γ and IP-10 might increase SE by lowering indeterminate rates. Point of care tests as the IP-10 LFI, which correlated fairly well with IP-10 MPA, should be further evaluated for the diagnosis of TB infection.
Herpesvirus Antibodies and Antigens in Patients With Cervical Anaplasia and in Controls 2
Authors: Alexander S. Pacsa, Lajos Kummerländer, Bela Pejtsik, Kalman Pali
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Herpesvirus Antibodies and Antigens in Patients With Cervical Anaplasia and in Controls Get access Alexander S. Pacsa, Ph.D., Alexander S. Pacsa, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lajos Kummerländer, M.D., Lajos Kummerländer, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Bela Pejtsik, M.D., Bela Pejtsik, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kalman Pali, M.D. Kalman Pali, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 4, October 1975, Pages 775–781, https://doi.org/10.1093/jnci/55.4.775 Published: 01 October 1975 Article history Received: 12 March 1975 Accepted: 23 May 1975 Published: 01 October 1975
Skin carcinogenesis in Ras/fos/PTEN null transgenic mice associates reveals mTOR association with papillomatogenesis/conversion and AKT with malignant progression
Authors: F.H. MacDonald, J.A. Quinn, D.A. Greenhalgh
Journal: British Journal of Dermatology (2011)

The conversion of benign tumour to malignancy depends on a complex combination of the genetic mutation milieu and the sentinel systems that resist carcinogenesis. In transgenic mouse skin carcinogenesis driven by rasHa/fos activation [HK1.ras/fos] and RU486-induced PTEN loss, we previously demonstrated that [HK1.ras/fos-Δ5PTENflx malignant conversion was delayed and progression limited to well-differentiated SSC histotypes [wdSCC]. This delay was associated with elevated p53/p21 expression until p53 was lost in late-stage papillomas, whereas p21 persisted and limit early-stage progression to wdSCCs. Given the regulation of AKT, and its target mTOR, by PTEN, we now determined their stage-specific expression profiles and found that, despite PTEN loss, expression of activated AKT [p-AKT] was low/absent in [HK1.ras/fos-Δ5PTENflx hyperplasia, papillomas and sporadic in wdSCCs. With time, p-AKT expression increased in p53 –negative wdSCCs and concomitant with this rise, punctate, nuclear p21 expression in basal layers became increasingly cytoplasmic, giving a peri-nuclear staining pattern. Hence early progression may involve an AKT-mediated exclusion of p21 from the nucleus, and once p-AKT expression became uniform in overt SCCs, p21 expression was undetectable. In being a major target of AKT activation, a similar profile was envisaged for m-TOR. However unlike p-AKT, p-mTOR was strongly expressed in [HK1.ras/fos-Δ5PTENflx hyperplasia, alongside strong p53/p21, persisted in p21 positive/p53 negative wdSCCs, but then faded on progression to aggressive SCCs, despite uniform p-AKT expression. These data suggest once p53 was lost, elevated [AKT-independent] p-mTOR expression cooperated with ras/fos in a converting role, whilst AKT expression exerts major effect in later progression via inhibition of p21.
Vulnerability to psychosis in unipolar major depression: is premorbid functioning involved?
Authors: J R Sands, M Harrow
Journal: American Journal of Psychiatry (1995)

This research examined whether deficits in premorbid functioning are associated with a vulnerability to psychosis in unipolar major depressive disorder.A group of 92 inpatients with unipolar major depression were assessed for premorbid functioning and psychotic symptoms during an index hospitalization. They were prospectively assessed for psychotic symptoms 2.0 and 4.5 years after hospital discharge.The psychotic depressed patients had significantly poorer premorbid functioning--particularly, adolescent social functioning--than the nonpsychotic depressed patients. Longitudinal analyses indicated that poor premorbid social adaptation was significantly associated with the emergence of psychosis during the follow-up period in depressed patients who had not been psychotic as inpatients.Factors related to a vulnerability to psychosis among patients with major depression are present even years before the onset of overt psychotic symptoms. The data could support the view that impaired premorbid functioning is one manifestation of prepsychotic processes that constitute an underlying diathesis for psychotic episodes during the longitudinal course of unipolar major depression. These findings are consistent with other emerging findings pointing to early developmental deficits in patients who subsequently develop psychotic disorders.
HP0010 Long-term effects of nonsteroidal antinflammatory drugs on human chondrocytes in alginate beads
Authors: C Sanchez, M Deberg, J-Y Reginster, Y Henrotin
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> This study was designed to compare the long-term effects (12 days) of nonsteroidal anti-inflammatory drugs (NSAID) on the metabolism of human chondrocytes cultured in alginate beads. Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium (DMEM +ITS+) for 12 days. Interleukin-6 and -8 (IL-6, IL-8), stromelysin (MMP-3) and aggrecan (AGG) productions were assayed by specific enzyme amplified sensitivity immunoassays (EASIA), and prostaglandin E2 (PGE2) production by a specific radioimmunoassay. All NSAID were tested at the mean peak plasmatic concentration (Cmax) obtained after oral administration of a therapeutic dose. The Cmax used in this study were 7.5 mg/ml for aceclofenac (ACECLO), 1.4 mg/ml for diclofenac (DICLO), 2 mg/ml for indomethacin (INDO), 3 mg/ml for nimesulide (NIM),1 mg/ml for rofecocib (ROFE), 0.7 mg/ml for celecoxib (CELE), 7 mg/ml for piroxicam (PIROX), and 25 mg/ml for ibuprofen (IBUP). At the therapeutic concentration, all NSAID tested fully blocked PGE2 production. Interestingly, ACECLO, DICLO, INDO, NIM and IBUP significantly inhibited both basal and IL-1b-stimulated IL-6 production, whereas ROFE, CELE and PIROX had no significant effects. No NSAID showed significant effects on basal and IL-1b-stimulated IL-8 production, excepted CELE and IBUP which slightly increased basal IL-8 production. ACECLO and INDO increased by 25% AGG content in the alginate beads, while the other NSAID were without significant effect. Furthermore, none NSAID were able to modify the inhibitory effect of IL-1b on AGG production. Finally, NSAID did not modify MMP-3 production. From this study, we can conclude that the mechanism of action of NSAID seems to be multifactorial and not limited to the inhibition of cyclooxygenases. Furthermore, in our culture conditions, at the Cmax and by comparison with other NSAID ACECLO and INDO show a advantageous profile of activity. They fully block PGE2 production, inhibit IL-6 synthesis and increase aggrecan synthesis. These effects would appear to be advantageous for the long-term treatment of chronic joint diseases such as osteoarthritis.
The breast differentiation antigen NY-BR-1: A novel target antigen for active immunotherapy in breast cancer
Authors: D. Jaeger, E. Saller, A. Zippelius, C. Frei, M. Gerlinger, T. Bartnick, E. Jaeger, A. Knuth
Journal: Journal of Clinical Oncology (2004)

2575 Background: There is evidence that the immune system interacts with cancer cells. This interaction influences the development of cancer and shapes the antigenic profile of emerging cancer cells. The identification of numerous tumor associated antigens that are recognized by autologous T cells opened new therapeutic perspectives for active immunotherapy. Here we report on the expression and immunogenicity of a novel breast differentiation antigen designated as NY-BR-1. Methods: SEREX technology was used to identify NY-BR-1 in a cDNA expression library of a breast cancer patient. The expression of NY-BR-1 was assessed and quantified in a series of healthy tissues, mammary and non-mammary tumors by RT-PCR and real time RT-PCR, respectively. Applying the reverse immunology approach, potential HLA-A2 binding peptide motifs were analyzed to assess CD8 T cell recognition. Results: NY-BR-1 is composed of 37 exons and has on open reading frame of 4.2 kb, encoding a peptide of Mr 158,000. It is expressed in normal breast, normal testis, and inconsistent in normal prostate; all other normal tissues were negative. In tumor tissues, NY-BR-1 mRNA expression was detected in 70% of breast cancer specimens. We identified 2 HLA-A*0201 restricted peptide epitopes that were recognized by CD8 T cell clones. They represent naturally processed NY-BR-1 epitopes, as cancer cells expressing HLA-A*0201 and NY-BR-1 will be lysed by these peptide specific T cell clones. Conclusions: These findings provide the rationale to consider NY-BR-1 as a target antigen for active immunotherapy in HLA-A*0201 positive patients with NY-BR-1 expressing breast cancer. No significant financial relationships to disclose.
A phase I study of cisplatin, tirapazamine and accelerated re-irradiation in unresectable recurrent head and neck cancer
Authors: E. E. W. Cohen, D. Rosine, E. Loh, D. J. Haraf, E. E. Vokes, J. Bourhis
Journal: Journal of Clinical Oncology (2004)

5511 Background: Head and neck cancer (HNC) patients will often experience local failure. Surgery is an accepted means of treating patients who have received prior full-dose radiotherapy (RT) although many patients are not surgical candidates and the procedures are often extensive. Re-irradiation offers a therapeutic option that can be locally palliative and rarely curative. Moreover, hypoxia within head and neck tumors has been implicated in resistance to therapy and recurrence. Tirapazamine (TPZ) has had promising effects when combined with cisplatin (CDDP) and RT as first-line therapy for advanced HNC. This Phase I trial was designed to test the feasibility of giving tirapazamine in the reirradiation setting. Methods: Inclusion criteria: recurrent HNC after prior RT, not amenable to standard therapy, recurrence primarily in sites that are amenable to RT, and no metastatic disease except “oligometastases”. Some patients were treated with palliative intent. The treatment regimen consisted of TPZ (260 mg/m2) and CDDP (50 mg/m2) weeks 1, 3, and 5, and TPZ (160 mg/m2) without CDDP days 1, 3, and 5 of week 2 for cohort 1 and of weeks 2 and 4 for cohort 2 in a phase I cohort design. RT was 7200 cGy in 42 fractions over 6 weeks with two daily fractions on the last 12 days. Results: 25 patients have received treatment: 7 and 18 patients on cohorts 1 and 2, respectively, from 10/01 to 11/03. The median dose of prior RT was 60 Gy and the median time to reirradiation was 22 mos. The median follow-up is 15 mo. Significant toxicities (grade 3 or higher) have been seen only in the RT port including grade 3 dermatitis and grade 3 mucositis. 4 fatalities occurred during the treatment period (2 pneumonias, 1 anoxic death, and 1 sudden death) and 1 additional death occurred due to carotid artery rupture 190 days after starting therapy. The median survival is 10 mos with actuarial 1-yr survival of 50%. The actuarial 1-yr progression-free survival is 19%. Conclusion: With limited follow-up, reirradiation with concomitant chemotherapy including TPZ is feasible without excessive toxicities in patients with unresectable recurrent HNC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Research Sanofi-Synthelabo