tbuckley/cabot-search huggingface dataset:
Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b–infected null responders
Authors: Kazuaki Chayama, Shoichi Takahashi, Joji Toyota, Yoshiyasu Karino, Kenji Ikeda, Hiroki Ishikawa, Hideaki Watanabe, Fiona McPhee, Eric Hughes, Hiromitsu Kumada
Journal: Hepatology (2011)

Patients with chronic hepatitis C virus (HCV) infection and previous null response to pegylated interferon (Peg-IFN) and ribavirin (RBV) have limited therapeutic options. HCV genotype 1 is the most common worldwide and the most difficult to treat; genotype 1b is the most common subtype of genotype 1 outside North America. The enhanced antiviral activity achieved by combining two direct-acting antiviral (DAA) agents may improve clinical outcomes. This open-label, phase IIa study included 10 patients with chronic HCV genotype 1b infection and previous null response (&lt;2 log10 reduction in HCV RNA after 12 weeks) to Peg-IFN and RBV. Patients received dual DAA treatment for 24 weeks with the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once-daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice-daily, then subsequently reduced to 200 mg twice-daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response (SVR) at 12 weeks post-treatment (SVR12). Nine patients completed 24 weeks of treatment; 1 patient discontinued treatment after 2 weeks. In the 9 patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all 9 patients achieved SVR12 and SVR24. HCV RNA also remained undetectable post-treatment in the patient who discontinued after 2 weeks. There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in 3 patients, but did not result in discontinuation. Conclusions : Dual therapy with daclatasvir and asunaprevir, without Peg-IFN and RBV, can achieve high SVR rates in difficult-to-treat patients with HCV genotype 1b infection and previous null response to Peg-IFN and RBV.
862 TRANSCRIPTIONAL-METABOLIC REPROGRAMMING OF HCV-INFECTION FROM PRIMARY HUMAN HEPATOCYTES CO-CULTURES TO CLINICAL SAMPLES
Authors: M.A. Guzzardi, N. Habib, D. Kitsberg, K. Uygun, M. Trippler, J. Timm, N. Friedman, Y. Nahmias
Journal: Journal of Hepatology (2012)
Randomised trial of two strategies offering women mobile screening for breast cancer.
Authors: E. M. Williams, M. P. Vessey
Journal: BMJ (1989)

The authors determined whether compliance would improve if a letter of invitation contained a definite appointment for breast cancer screening rather than an open ended request to make an appointment. A sample of 450 women aged 45-64 was identified from the age-sex registers of two general practitioners from one practice in Aylesbury and randomly allocated to receive either a letter with an appointment (group 1) or an open ended letter of invitation (group 2) for breast cancer screening
Closing the Gaps: From Science to Action in Maternal, Newborn, and Child Health in Africa
Authors: Sara Bennett, Freddie Ssengooba
Journal: PLoS Medicine (2010)

This essay focuses on the  to policy and  gap and addresses what is already known about how scientific evidence has influenced maternal newborn and child health (MNCH) policy and practice. In addition it considers some of the key challenges in closing the science to policy and practice gap and concludes by identifying promising paths for future action.
Human OX40 tunes the function of regulatory T cells in tumor and nontumor areas of hepatitis C virus-infected liver tissue
Authors: Silvia Piconese, Eleonora Timperi, Ilenia Pacella, Valeria Schinzari, Claudio Tripodo, Massimo Rossi, Nicola Guglielmo, Gianluca Mennini, Gian Luca Grazi, Simona Di Filippo, Stefania Brozzetti, Katia Fazzi, Guido Antonelli, Maria Antonietta Lozzi, Massimo Sanchez, Vincenzo Barnaba
Journal: Hepatology (2014)

Regulatory T cells (Tregs) can be considered as a mixed population of distinct subsets, endowed with a diverse extent and quality of adaptation to microenvironmental signals. Here, we uncovered an opposite distribution of Treg expansion, phenotype, and plasticity in different microenvironments in the same organ (liver) derived from patients with chronic hepatitis C: On the one side, cirrhotic and tumor fragments were moderately and highly infiltrated by Tregs, respectively, expressing OX40 and a T-bethighIFN-γ– “T-helper (Th)1-suppressing” phenotype; on the other side, noncirrhotic liver specimens contained low frequencies of Tregs that expressed low levels of OX40 and highly produced interferon-gamma (IFN-γ; T-bet+IFN-γ+), thus becoming “Th1-like” cells. OX40-expressing and Th1-suppressing Tregs were enriched in the Helios-positive subset, carrying highly demethylated Treg cell-specific demethylated region that configures committed Tregs stably expressing forkhead box protein 3. OX40 ligand, mostly expressed by M2-like monocytes and macrophages, boosted OX40+ Treg proliferation and antagonized the differentiation of Th1-like Tregs. However, this signal is counteracted in noncirrhotic liver tissue (showing various levels of inflammation) by high availability of interleukin-12 and IFN-γ, ultimately leading to complete, full Th1-like Treg differentiation. Conclusion : Our data demonstrate that Tregs can finely adapt, or even subvert, their classical inhibitory machinery in distinct microenvironments within the same organ. (Hepatology 2014;60:1494–1507)
Behavioral Health Services for Women Who Have Breast Cancer
Authors: Vanessa Azzone, Richard G. Frank, Juliana R. Pakes, Craig C. Earle, Michael J. Hassett
Journal: Journal of Clinical Oncology (2008)

To explore whether the use of behavioral health services (BHS) among women with breast cancer is influenced by how insurance plans administer these services, we compared utilization of psychotherapy and psychotherapeutic medications among women with breast cancer who received BHS coverage through a carve-out versus integrated arrangement.We analyzed insurance claims, enrollment data, and benefit design data from the MarketScan Commercial Claims & Encounters Research Database for the years 1998 to 2002 for women <or= 63 years old with newly diagnosed breast cancer. We compared the probability of receiving psychotherapy, the likelihood of receiving antidepressant/antianxiety/hypnotic medications, and the number of psychotherapy sessions used during the year after a breast cancer diagnosis among women whose behavioral health services were provided through carve-out versus integrated arrangements.Women enrolled in carve-outs were significantly less likely to receive any psychotherapy visits compared with women in integrated arrangements (odds ratio, 0.68; P < .01). Conditional on having received psychotherapy, however, women in carve-out arrangements used more psychotherapy visits than women in integrated arrangements. The use of antianxiety/hypnotic drugs was significantly higher for women in carve-out arrangements versus women in integrated arrangements (36.1% v 32.6%, P < .05). Moreover, women who received psychotherapy were significantly more likely to received antidepressants and antianxiety/hypnotic medications (five and three times more likely, respectively).The type of BHS arrangement was associated with the utilization of psychotherapy and psychotherapeutic medications among women with breast cancer.
Doctors fighting, fleeing, or facing up to death
Authors: J. Goodall
Journal: BMJ (1998)

It can be disturbing to consider medical practice as portrayed by the media. On the one hand, we hear of living wills, intended to forestall artificial prolongation of dying. On the other hand,incurable patients—and parents of incurably ill babies—are sometimes finding doctors who will hasten death. If these extremes are there how do they arise?

My reflections about this were fuelled when three of my good friends died within a two week period. In their dying, they showed some of the emotional reactions to loss which doctors can so readily identify in others while imagining themselves to be immune.

The non-medical friend, dying several months after surgery for ovarian cancer, had never admitted to declining health but kept speaking hopefully of improvement ahead. One of the doctors, with inexorably worsening cerebellar ataxia, had rejected offers of palliative therapy, fearing stupefaction. Instead, too unsteady to act for herself, she repeatedly asked her general practitioner andher husband …
Polychlorinated biphenyl induction of hepatocellular carcinoma in the Sprague-Dawley rat.
Authors: D H Norback, R H Weltman
Journal: Environmental Health Perspectives (1985)

Male and female Sprague-Dawley rats (70 males and 70 females in the initial group) were fed a diet containing a polychlorinated biphenyl mixture (Aroclor 1260, 100 ppm for 16 months and 50 ppm for an additional 8 months) for 2 years followed by a control diet for 5 months. A control group initially consisted of 63 males and 63 females. Sequential morphologic changes were evaluated throughout the study. In the PCB-exposed group the following hepatocellular lesions developed in sequence: centrolobular cell hypertrophy at 1 month, foci of cell alteration at 3 months, areas at 6 months, neoplastic nodules at 12 months, trabecular carcinoma at 15 months, and adenocarcinoma at 24 months. In addition, simple and cystic cholangioma at 18 and 23 months, respectively, and adenofibrosis at 22 months were present. With the exception of hepatocyte hypertrophy and adenofibrosis, all lesions contained cells that were positive for gamma glutamyl transpeptidase activity. In the PCB-exposed group that was examined after 18 months, hepatocellular neoplasms were present in 95% of the 47 females and in 15% of the 46 males. Distant organ metastases did not occur and the mortality rate was not increased in the PCB exposed group. In 81 control rats examined after the 18th month, only 1 hepatocellular neoplasm (a neoplastic nodule) occurred. PCB- exposed and control rats developed simple cholangioma, cystic cholangioma and adenofibrosis; the incidence of each was greater in the PCB group. Thus, within the Sprague-Dawley rat group exposed to a diet with relatively high concentrations of Aroclor 1260 for 2 years a hepatocarcinogenic effect manifested by formation of slowly growing hepatocellular carcinomas was produced.
Defective High-Density Lipoprotein Composition in Patients on Chronic Hemodialysis
Authors: Jayson Rapoport, Michael Aviram, Cidio Chaimovitz, J. Gerald Brook
Journal: New England Journal of Medicine (1978)

We determined serum high-density lipoprotein cholesterol content and analyzed the apoprotein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean ±1 standard deviation: 26±13 vs. 52±9 mg per 100 ml; P<0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P<0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in "arginine-rich" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein CII in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein CII. (N Engl J Med 299:1326–1329, 1978)
The Choice: Lewellys F. Barker and the Full-Time Plan
Authors: Charles S. Bryan, M. Shawn Stinson
Journal: Annals of Internal Medicine (2002)

In 1914, Lewellys F. Barker, William Osler's successor as Professor of Medicine and physician-in-chief at Johns Hopkins University School of Medicine, resigned to enter private practice rather than accept the terms of a full-time plan, whereby professors in clinical departments would be salaried like other professors in the university. Barker had been an early proponent of the full-time plan. His decision reflected not only a personal desire for a larger income but also contradictions inherent in the Flexnerian ideal of clinical medicine as a research-oriented university discipline devoid of financial incentives to see patients. In private practice, Barker maintained a high profile as a teacher, writer, supporter of the Johns Hopkins medical institutions, and public figure. The issues raised by his difficult decision remain relevant and have not been satisfactorily resolved.
Abstract 2840: Efficacy of radiation therapy in mammary carcinomas is regulated by macrophages
Authors: Stephen L. Shiao, David G. DeNardo, Kerri A. Fujikawa, Bruce A. Faddegon, Catherine C. Park, Lisa M. Coussens
Journal: Cancer Research (2011)

Abstract In patients with locally advanced breast cancer, radiation therapy (RT) and chemotherapy following surgery has been a mainstay of treatment with demonstrated survival advantage in numerous randomized trials. However, despite recent advances in treatment, many women still ultimately succumb to disease highlighting the need to improve therapeutic strategies. Results from several groups have recently revealed that the therapeutic effects of RT are in part dependent on activation of immune-mediated mechanism(s); however, little is known regarding the mechanistic details of this activation. To address this, we examined changes in the immune microenvironment of mammary carcinomas following RT. We found that following RT (5 Gy), the density of infiltrating macrophages was significantly increased (20 vs 35%, p = 0.02) as compared to mammary tumors in mice not receiving RT. When macrophages were depleted following RT, via use of a CSF-1 antagonist, a significant delay in tumor growth, as compared to tumors treated with RT alone was observed. Since this data indicated that macrophage infiltration blunted RT responsiveness, we hypothesized that reprogramming tumor-infiltrating macrophages more towards a classical cytotoxic phenotype would result in enhanced RT response and delayed tumor re-growth. Thus, we treated tumor-bearing mice with anti-IL-4 neutralizing mABs in combination with RT, and evaluated tumor re-growth, as compared to tumor-bearing mice treated with either RT or anti-IL4 mAB alone, and found that indeed, reprogramming tumor-infiltrating macrophages to favor classical (M1)-type activity significantly enhanced RT response and delayed tumor re-growth. Together these studies indicate that: 1) RT induces macrophage infiltration into mammary tumors, 2) protumor-type macrophages infiltrating mammary carcinomas blunt response to RT, and 3) reprogramming of tumor-infiltrating macrophages to favor a cytotoxic phenotype improves efficacy of RT. This work was supported by grants from the NIH/NCI, and Era of Hope (W81XWH-06-1-0416), and Program in Mesothelioma (PR080717) grants from the Department of Defense to LMC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2840. doi:10.1158/1538-7445.AM2011-2840
Sudden Death and Ischemic Heart Disease
Authors: T. W. Anderson, W. H. le Riche, J. S. MacKay
Journal: New England Journal of Medicine (1969)

Investigations conducted in several parts of the world have shown that residents of soft-water areas have a higher death rate from ischemic heart disease than residents of hard-water areas. The same pattern appears to exist in Ontario, but when deaths are divided into sudden and nonsudden (on the basis of whether or not the death certificate was signed by a coroner), the higher death rate in the soft-water areas is found to be due entirely to an excess of sudden deaths. This finding suggests that the correlation between cardiac mortality and water hardness may be the result of an increased susceptibility to lethal arrhythmias among residents of soft-water areas.
Phenytoin as an Antimanic Anticonvulsant: A Controlled Study
Authors: A. Mishory, Y. Yaroslavsky, Y. Bersudsky, R.H. Belmaker
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Phenytoin, a classical anticonvulsant, shares with antimanic anticonvulsants the property of blockade of voltage-activated sodium channels. The authors therefore planned a trial of phenytoin for mania. METHOD: Patients with either bipolar I disorder, manic type, or schizoaffective disorder, manic type, entered a 5-week, double-blind controlled trial of haloperidol plus phenytoin versus haloperidol plus placebo. Of 39 patients, 30 completed at least 3 weeks and 25 completed 5 weeks. RESULTS: Significantly more improvement was observed in the patients receiving phenytoin. Added improvement with phenytoin in scores on the Brief Psychiatric Rating Scale and Clinical Global Impression was seen in the patients with bipolar mania but not those with schizoaffective mania. CONCLUSIONS: Blockade of voltage-activated sodium channels may be a common therapeutic mechanism of many anticonvulsants given for mania, and phenytoin may be a therapeutic option for some manic patients.
Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia
Authors: William G. Wierda, Thomas J. Kipps, Michael J. Keating
Journal: Journal of Clinical Oncology (2005)

Immune-based treatments represent a new group of therapeutic strategies for patients with cancer, including chronic lymphocytic leukemia (CLL), that employ immune effector mechanisms. Among these strategies is passive immunotherapy with monoclonal antibody, alone or in combination with chemotherapy. Active immunotherapy strategies currently under development include vaccines, administration of expanded and activated T cells, and allogeneic stem cell transplantation. These immune-based strategies represent new treatments with potentially complementary mechanisms of action to standard therapies and signify major advances in treatments for patients with CLL.
Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B
Authors: Nobuyuki Hizawa, Etsuro Yamaguchi, Eisei Jinushi, Satoshi Konno, Yoshikazu Kawakami, Masaharu Nishimura
Journal: Journal of Allergy and Clinical Immunology (2001)
Miracle cures advertised on the internet
Authors: A. Brooks
Journal: BMJ (1998)

Enforcement agencies from 20 countries last week “swept” the internet for potentially misleading health claims and miracle cures. The exercise turned up advertisements for a herbal remedy claimed to help patients become free of cancer within 10-14 days, books that claimed to contain “the cures for all cancers, all diseases and for HIV and AIDS,” and a slimming soap from …
Response to Letters Regarding Article, “Abnormal Conduction and Morphology in the Atrioventricular Node of Mice with Atrioventricular Canal Targeted Deletion of Alk3/Bmpr1a Receptor”
Authors: Dina Myers Stroud, Cindy Yu, Glenn I. Fishman, Gregory E. Morley, Vinciane Gaussin, John B.E. Burch, Yuji Mishina, Michael D. Schneider
Journal: Circulation (2008)
Activation of peroxisome proliferator-activated receptor-α inhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia-reperfusion
Authors: Marta Massip-Salcedo, Amine M. Zaouali, Susagna Padrissa-Altés, Arani Casillas-Ramirez, Joan Rodés, Joan Roselló-Catafau, Carmen Peralta
Journal: Hepatology (2007)

Hepatic steatosis is a major risk factor in ischemia–reperfusion (I/R). Adiponectin acts as an antiobesity and anti-inflammatory hormone. Adiponectin activates peroxisome proliferator-activated receptor-α (PPAR-α), a transcription factor that regulates inflammation in liver disease. Ischemic preconditioning (PC) based on brief periods of I/R protects steatotic livers against subsequent sustained I/R injury, but just how this is achieved is poorly understood. This study explains the role of PPAR-α and adiponectin in the vulnerability shown by steatotic livers to I/R and the benefits of PC in this situation. PPAR-α and adiponectin levels in nonsteatotic livers undergoing I/R were similar to those found in the sham group. However, reduced PPAR-α and increased adiponectin levels, particularly the high molecular weight isoform, were observed in steatotic livers as a consequence of I/R. Our results suggest that mitogen-activated protein kinases (MAPKs) may be positive regulators of adiponectin accumulation in steatotic livers. The addition of adiponectin small interfering RNA (siRNA) before I/R protected steatotic livers against oxidative stress and hepatic injury. The induction of PC before I/R increased PPAR-α and reduced adiponectin levels in steatotic livers. PC, which increased PPAR-α, as well as PPAR-α agonist pretreatment reduced MAPK expression, adiponectin, oxidative stress, and hepatic injury that follows I/R. In addition, the administration of a PPAR-α antagonist in preconditioned steatotic livers eliminated the beneficial effects of PC on MAPKs, adiponectin, oxidative stress, and hepatic injury. Conclusion : Steatotic livers are more predisposed to down-regulate PPAR-α and overexpress adiponectin when subjected to I/R. PPAR-α agonists and adiponectin siRNA are promising candidates to protect steatotic livers. PPAR-α agonists as well as PC, through PPAR-α, inhibited MAPK expression following I/R. This in turn inhibited adiponectin accumulation in steatotic livers and adiponectin-worsening effects on oxidative stress and hepatic injury. (Hepatology 2007.)
Epidemics of fractures during periods of snow and ice.
Authors: Z A Ralis
Journal: BMJ (1986)

Recovery was uneventful and during the subsequent five years the pericardial effusion did not reaccumulate.Blood films showed sc'anty if any acanthocytes but lipoprotein values remained consistent with hypobetalipoproteinaemia.Famtily study-The table gives the results of lipoprotein analysis in family members.Hypobetalipoproteinaemia is recorded when the -low density lipoprotein cholesterol concentration is below-the age and sex related fifth percentile in our laboratory.The patient had acanthocytes in her preoperative blood films.Other family members did not.Each family member was found to be asympto- matic and normal on physical examination.Each had a normal chest x ray picture and echocardiogram.
Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia
Authors: A M Eiring, B D G Page, I L Kraft, C C Mason, N A Vellore, D Resetca, M S Zabriskie, T Y Zhang, J S Khorashad, A J Engar, K R Reynolds, D J Anderson, A Senina, A D Pomicter, C C Arpin, S Ahmad, W L Heaton, S K Tantravahi, A Todic, R Colaguori, R Moriggl, D J Wilson, R Baron, T O'Hare, P T Gunning, M W Deininger
Journal: Leukemia (2014)
Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48
Authors: Saima Riazuddin, Inna A Belyantseva, Arnaud P J Giese, Kwanghyuk Lee, Artur A Indzhykulian, Sri Pratima Nandamuri, Rizwan Yousaf, Ghanshyam P Sinha, Sue Lee, David Terrell, Rashmi S Hegde, Rana A Ali, Saima Anwar, Paula B Andrade-Elizondo, Asli Sirmaci, Leslie V Parise, Sulman Basit, Abdul Wali, Muhammad Ayub, Muhammad Ansar, Wasim Ahmad, Shaheen N Khan, Javed Akram, Mustafa Tekin, Sheikh Riazuddin, Tiffany Cook, Elke K Buschbeck, Gregory I Frolenkov, Suzanne M Leal, Thomas B Friedman, Zubair M Ahmed
Journal: Nature Genetics (2012)