tbuckley/cabot-search huggingface dataset:
Macrophages sustain HIV replication in vivo independently of T cells
Authors: Jenna B. Honeycutt, Angela Wahl, Caroline Baker, Rae Ann Spagnuolo, John Foster, Oksana Zakharova, Stephen Wietgrefe, Carolina Caro-Vegas, Victoria Madden, Garrett Sharpe, Ashley T. Haase, Joseph J. Eron, J. Victor Garcia
Journal: Journal of Clinical Investigation (2016)

Macrophages have long been considered to contribute to HIV infection of the CNS; however, a recent study has contradicted this early work and suggests that myeloid cells are not an in vivo source of virus production. Here, we addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. We were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. To determine whether tissue macrophages are productively infected, we used 3 different but complementary humanized mouse models. Two of these models (bone marrow/liver/thymus [BLT] mice and T cell–only mice [ToM]) have been previously described, and the third model was generated by reconstituting immunodeficient mice with human CD34+ hematopoietic stem cells that were devoid of human T cells (myeloid-only mice [MoM]) to specifically evaluate HIV replication in this population. Using MoM, we demonstrated that macrophages can sustain HIV replication in the absence of T cells; HIV-infected macrophages are distributed in various tissues including the brain; replication-competent virus can be rescued ex vivo from infected macrophages; and infected macrophages can establish de novo infection. Together, these results demonstrate that macrophages represent a genuine target for HIV infection in vivo that can sustain and transmit infection.
Abstract P069: Prognostic Impact of the Omega-3 Index in Chest Pain Patients With a Suspected Acute Coronary Syndrome and Low Dietary Intake of Omega-3
Authors: Ricardo A Leon de la Fuente, Patrycja A Naesgaard, Stein Tore Nilsen, Torbjoern Aarsland, Leik Woie, Silvia Dib Ashur, Thomas E Gundersen, Tore Bolstad, Harry Staines, William S Harris, Dennis W Nilsen
Journal: Circulation (2012)

Background: Epidemiological and interventional studies suggest that omega-3 (n-3) fatty acids derived from fish oil can reduce the occurrence of cardiovascular disease. Based on these observations, the omega-3 index [eicosapantaenoic acid (EPA) + docosahexaenoic acid (DHA) content in cell red blood membranes] has been suggested as a novel risk marker for cardiac death. Objective: To assess whether the omega-3 index can predict all-cause mortality, cardiac death and sudden cardiac death (SCD) following hospitalization with an acute coronary syndrome (ACS). Material and methods: The omega-3 index was measured in 572 consecutive patients admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit essentially based on red meat and a low intake of fish. The median age of the included patients was 63 years and 59 % were males. Clinical endpoints were collected during a 5-year follow-up period, median 3.64 years, range 1 day to 5.46 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. In our multivariable analysis we corrected for age, sex, arterial hypertension, diabetes, smoking history, body mass index, previous coronary heart disease, high-sensitivity C-reactive protein, brain natriuretic peptide, Troponin-T release and use of statins and beta-blockers. Results: No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median omega 3-index was 2.8%, and ranging from 1.9% in the lowest to 3.8% in the highest quartile. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. Conclusions: In a population with a low intake of fish and fish oils, the omega-3 index did not predict future fatal events in patients with acute chest pain and suspected ACS, suggesting that index levels less than 4% are too low to be protective.
Long-term survival in patients with para-aortic lymph node metastasis with systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in endometrial carcinoma
Authors: M. Hiura, T. Nogawa, T. Matsumoto, T. Yokoyama, Y. Shiroyama, J. Wroblewski, E. Hirata
Journal: Journal of Clinical Oncology (2007)

16011 Background: The purpose of this study was to assess modified radical hysterectomy including systematic pelvic and para- aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for a long-term survival over the past 10 years. Methods: Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy, and peritoneal cytology in 284 endometrial carcinoma patients who gave an informed consent at the Department of Gynecologic Oncology of Shikoku Cancer Center. The patients with a tumor confined to the uterus (stage Ic and II) were treated by 3 courses of CEP (cyclophosphamide 750 mg/m 2 , epirubicin 50 mg/m 2 , cisplatin 75 mg/m 2 ) regimen 3–4weeks apart, extrauterine lesions involving adnexa and/or pelvic lymph node (PLN), and para-aortic lymph node (PAN) metastasis were treated by 5 and 10 courses, respectively. Multivariate analysis was performed for the prognostic factors and actuarial technique for the survival rate. Results: PLN and PAN metastasis were 9.2% (26/284) and 7.4% (21/284), respectively. The univariate analysis of prognostic factors revealed that FIGO clinical stage, histology, myometrial invasion, adnexal metastasis, lymphvascular space invasion, tumor diameter, peritoneal cytology and retroperitoneal lymph node (RLN) metastasis were significantly associated with 10-year overall survival. A multivariate analysis showed that adnexal metastasis (p=0.0418) and lymphvascular space invasion (p=0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year survival in patients with negative and positive para-aortic lymph node were 96%, 72% and 93%, 62%, respectively (p=0.006). Conclusions: We conclude that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy might improve a long-term survival in patients with PAN metastasis in endometrial carcinoma. No significant financial relationships to disclose.
Effects of Diethyl Maleate on Aryl Hydrocarbon Hydroxylase and on 3-Methyl-cholanthrene-Induced Skin Tumorigenesis in Rats and Mice2
Authors: A. H. L. Chuang, Hasan Mukhtar, Edward Bresnick
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Effects of Diethyl Maleate on Aryl Hydrocarbon Hydroxylase and on 3-Methyl-cholanthrene-Induced Skin Tumorigenesis in Rats and Mice Get access A. H. L. Chuang, A. H. L. Chuang Search for other works by this author on: Oxford Academic PubMed Google Scholar Hasan Mukhtar, Hasan Mukhtar Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward Bresnick Edward Bresnick 6 6Address reprint requests to Dr. Bresnick. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 2, February 1978, Pages 321–325, https://doi.org/10.1093/jnci/60.2.321 Published: 01 February 1978 Article history Received: 28 April 1976 Revision received: 02 May 1977 Accepted: 29 August 1977 Published: 01 February 1978
Changing oral vaccine to inactivated polio vaccine might increase mortality
Authors: Eleanor N Fish, Kate L Flanagan, David Furman, Sabra L Klein, Tobias R Kollmann, Dorthe L Jeppesen, Ofer Levy, Arnaud Marchant, Siva Namachivayam, Mihai G Netea, Magdalena Plebanski, Sarah L Rowland-Jones, Liisa K Selin, Frank Shann, Hilton C Whittle
Journal: The Lancet (2016)
European scheme to develop drugs for diseases with no treatment launched
Authors: Nigel Hawkes
Journal: BMJ (2016)

The European Medicines Agency (EMA) has launched a scheme to speed up the development of new drugs that target diseases with no existing treatment.

Aimed at smaller companies and academic researchers, PRIME (PRIority MEdicines) aims to streamline the development process by offering early advice on clinical trial design. It said that much effort is wasted, especially by those less experienced in drug development, by poorly designed trials that do not address the issues needed for marketing authorisation.

Unlike the UK’s Early Access to Medicines scheme, PRIME does not shorten the authorisation procedure. Under the UK scheme drugs may be given market access if they show sufficient promise before a …
Pregnancy Toxaemia and Hypertension
Authors: S V SUKHORUKIKH
Journal: BMJ (1965)

MEDICAL JORNAL ground to this the charter asks in effect that the doctor should be treated as a responsible person ready and anxious to do a job of work free from pettifogging restrictions.All these matters have been discussed almost ad nauseam in our correspondence pages, in editorial articles, in debates up and down the country by the many persons and institutions con- cerned to see general practice put on a sound basis and freed from the recurring crises that seem to be characteristic of it, not only in this but in other countries.So far as Britain's N.H.S. is concerned, the obstacle at the moment is what has been called " pricing the contract."Practitioners have been disappointed, even dismayed, by the two recent awards of the Review Body-the 14% award of 1963 and the £5-m.award of 1965.They should pause to reflect that they are not the only aggrieved persons, and that, as letters in this journal have pointed out, junior hospital staff and senior hospital medical officers are by no means contented with their lot.Those representing general practitioners have obviously sought to negotiate the cost of the new
A commitment law for patients, doctors, and lawyers
Authors: L H Roth
Journal: American Journal of Psychiatry (1979)

The author proposes a model commitment law that balances the sometimes conflicting points of view among patients, doctors, and lawyers about this subject. Paternalism is affirmed, while safeguards are provided. It is argued that absent patient incompetency to consent to or refuse treatment, or absent an emergency, mental patients should not be treated involuntarily. The author believes that a different procedural approach is required depending on whether the patient is committed under the parens patriae or police power of the state.
Comparative transcriptomics reveals the conserved building blocks involved in parallel evolution of diverse phenotypic traits in ants
Authors: Claire Morandin, Mandy M. Y. Tin, Sílvia Abril, Crisanto Gómez, Luigi Pontieri, Morten Schiøtt, Liselotte Sundström, Kazuki Tsuji, Jes Søe Pedersen, Heikki Helanterä, Alexander S. Mikheyev
Journal: Genome biology (2016)

Abstract Background Reproductive division of labor in eusocial insects is a striking example of a shared genetic background giving rise to alternative phenotypes, namely queen and worker castes. Queen and worker phenotypes play major roles in the evolution of eusocial insects. Their behavior, morphology and physiology underpin many ecologically relevant colony-level traits, which evolved in parallel in multiple species. Results Using queen and worker transcriptomic data from 16 ant species we tested the hypothesis that conserved sets of genes are involved in ant reproductive division of labor. We further hypothesized that such sets of genes should also be involved in the parallel evolution of other key traits. We applied weighted gene co-expression network analysis, which clusters co-expressed genes into modules, whose expression levels can be summarized by their ‘eigengenes’. Eigengenes of most modules were correlated with phenotypic differentiation between queens and workers. Furthermore, eigengenes of some modules were correlated with repeated evolution of key phenotypes such as complete worker sterility, the number of queens per colony, and even invasiveness. Finally, connectivity and expression levels of genes within the co-expressed network were strongly associated with the strength of selection. Although caste-associated sets of genes evolve faster than non-caste-associated, we found no evidence for queen- or worker-associated co-expressed genes evolving faster than one another. Conclusions These results identify conserved functionally important genomic units that likely serve as building blocks of phenotypic innovation, and allow the remarkable breadth of parallel evolution seen in ants, and possibly other eusocial insects as well.
Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation
Authors: Fatemeh Ravar, Ebrahim Saadat, Mehdi Gholami, Pouya Dehghankelishadi, Mehdi Mahdavi, Samira Azami, Farid A. Dorkoosh
Journal: Journal of Controlled Release (2016)
Unilateral vanishing lung syndrome
Authors: Marco Anile, Daniele Diso, Ilaria Onorati, Sara Mantovani, Federico Venuta
Journal: Thorax (2016)

A 14-year-old boy was admitted with mild right chest pain, exercise dyspnoea and occasional palpitations. There was no smoking history. There was no past medical history of recurrent chest infections. The physical examination revealed an absence of breath sounds and hyper-resonance of the right hemithorax. A chest X-ray showed unilateral massive bullous disease with radiolucency of right lung and flattening of the right hemidiaphragm (figure 1A). The high-resolution chest CT scan confirmed …
P-249 Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003) - an analysis of surgeons vs oncologists
Authors: I. Iwanaga, S. Yuki, H. Fukushima, N. Takahashi, T. Shichinohe, T. Kusumi, F. Nakamura, S. Sogabe, K. Hatanaka, K. Oomori, K. Misawa, N. Senmaru, K. Iwai, T. Shinohara, M. Koike, K. Miyashita, T. Amano, Y.M. Ito, N. Sakamoto, A. Taketomi, S. Hirano, Y. Komatsu
Journal: Annals of Oncology (2015)
Abstract 15275: Altered Extracellular Matrix Proteoglycan- Decorin, Collagens and Elastin Deposition May Enhance Atherosclerosis in Human Peripheral Artery Disease: Implication of Morphological Predictors in Restenotic Plaque Progression
Authors: Prakash Krishnan, Purushothaman K-Raman, Meerarani Purushothaman, Jason C Kovacic, Usman Baber, Arthur Tarricone, Miguel Vasquez, Jose Wiley, Annapoorna Kini, Samin K Sharma, Valentin Fuster, Pedro R Moreno
Journal: Circulation (2015)

Introduction: In coronary artery restenosis, reduced proteoglycan-decorin deposition in extracellular matrix (ECM) was shown to be associated with alterations in the types of collagens in ECM. However, in Peripheral Artery Disease (PAD) restenosis, these ECM changes have not been carefully characterized. Alterations in proteoglycan-decorin expression in the ECM may change the fibrillar architecture of collagens, and may alter the type of collagen deposition. HYPOTHESIS: We hypothesize that in PAD restenotic plaques, decreased deposition of proteoglycan-decorin is associated with increased type III collagen and elastin with decreased type I collagen content when compared to de novo control plaques. Methods: Thirteen restenotic and thirteen de novo superficial femoral artery plaques were obtained in-vivo during peripheral artery interventional procedure and compared histopathologically for ECM changes. Protein expression profiles of decorin, type I and type III collagen, and elastin deposition were evaluated and graded by immunohistochemistry. H&amp; E stain was used to characterize the plaque morphology and stellate cell grade by scoring. Results: (See figure and table). In restenotic atheroma decorin, and type I collagen were decreased (p= 0.0001 for all comparisons). Type III collagen and elastin content were increased (p= 0.0001 for all comparisons) compared to de novo plaques. Conclusions: In PAD restenosis, we observed a reduction in decorin with an increase in type III collagen and simultaneous decrease in type I collagen as reported in CAD restenosis. Reparative injurious processes may underlie the associated observation in reduced proteoglycan-decorin in the ECM and altered types of collagen content. Additional molecular biological studies will address the mechanistic mediators which cause these ECM compositional changes.
Safety of Fluticasone plus Salmeterol in Asthma — Reassuring Data, but No Final Answer
Authors: Fernando D. Martinez
Journal: New England Journal of Medicine (2016)

After the introduction of the long-acting beta-agonist (LABA) salmeterol for the treatment of asthma, two large trials — the Salmeterol Multicenter Asthma Research Trial (SMART),1 which was mandated by the Food and Drug Administration (FDA) and involved 26,000 patients, and the Serevent Nationwide Surveillance (SNS) trial2 in the United Kingdom, which involved 25,000 patients — showed a higher risk of asthma-related death among patients receiving salmeterol than among those receiving placebo. A second LABA, formoterol, was introduced some years later, and although no such large studies were available for this drug, the aggregate evidence showed that patients taking this drug . . .
Quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design
Authors: Justin D. Smith, Sundari Suresh, Ulrich Schlecht, Manhong Wu, Omar Wagih, Gary Peltz, Ronald W. Davis, Lars M. Steinmetz, Leopold Parts, Robert P. St.Onge
Journal: Genome biology (2016)

Genome-scale CRISPR interference (CRISPRi) has been used in human cell lines; however, the features of effective guide RNAs (gRNAs) in different organisms have not been well characterized. Here, we define rules that determine gRNA effectiveness for transcriptional repression in Saccharomyces cerevisiae.
Drug allergies documented in electronic health records of a large healthcare system
Authors: L. Zhou, N. Dhopeshwarkar, K. G. Blumenthal, F. Goss, M. Topaz, S. P. Slight, D. W. Bates
Journal: Allergy (2016)

The prevalence of drug allergies documented in electronic health records (EHRs) of large patient populations is understudied.We aimed to describe the prevalence of common drug allergies and patient characteristics documented in EHRs of a large healthcare network over the last two decades.Drug allergy data were obtained from EHRs of patients who visited two large tertiary care hospitals in Boston from 1990 to 2013. The prevalence of each drug and drug class was calculated and compared by sex and race/ethnicity. The number of allergies per patient was calculated and the frequency of patients having 1, 2, 3…, or 10+ drug allergies was reported. We also conducted a trend analysis by comparing the proportion of each allergy to the total number of drug allergies over time.Among 1 766 328 patients, 35.5% of patients had at least one reported drug allergy with an average of 1.95 drug allergies per patient. The most commonly reported drug allergies in this population were to penicillins (12.8%), sulfonamide antibiotics (7.4%), opiates (6.8%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (3.5%). The relative proportion of allergies to angiotensin-converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors (statins) have more than doubled since early 2000s. Drug allergies were most prevalent among females and white patients except for NSAIDs, ACE inhibitors, and thiazide diuretics, which were more prevalent in black patients.Females and white patients may be more likely to experience a reaction from common medications. An increase in reported allergies to ACE inhibitors and statins is noteworthy.
Effect of Cytokine Therapy on Survival for Patients With Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Madhu Mazumdar, Jennifer Bacik, Paul Russo, William J. Berg, Erica M. Metz
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the relationship between treatment with cytokine therapy and survival, investigate the effect of nephrectomy on survival, and identify long-term survivors among a cohort of 670 patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 670 patients with advanced RCC treated on 24 clinical trials of systemic chemotherapy or cytokine therapy were the subjects of this retrospective analysis. Treatment was categorized as cytokine (containing interferon alfa and/or interleukin-2) in 396 patients (59%) and as chemotherapy (cytotoxic or hormonal therapy) in 274 (41%). Among the 670 patients, those with survival times of greater than 5 years were identified as long-term survivors. RESULTS: Patients treated with cytokine therapy had a longer survival time than did those treated with chemotherapy, regardless of the year of treatment or risk category based on pretreatment features. The median survival times for favorable-, intermediate-, and poor-risk patients were 27, 12, and 6 months for those treated with cytokines and 15, 7, and 3 months for those treated with chemotherapy, respectively. The magnitude of difference in median survival was greater in the favorable- and intermediate-risk groups. The median survival time was less than 6 months in the poor-risk group for both treatment programs. Median survival time was 14 months among patients with prior nephrectomy plus time from diagnosis to treatment greater than 1 year versus 8 months among those with time from diagnosis to treatment less than 1 year, regardless of pretreatment nephrectomy status. Thirty patients (4.5%) among the 670 patients were identified as long-term survivors; 12 were free of disease after nephrectomy and treatment with interferon alfa, interleukin-2, or surgical resection of metastasis. CONCLUSION: The low proportion of patients with advanced RCC who achieve long-term survival emphasizes the need for clinical investigation to identify more effective therapy.
PML as a potential predictive factor of efficacy of oxaliplatin based first line chemotherapy in colorectal cancer patients
Authors: B. Vincenzi, G. Perrone, D. Santini, F. Loupakis, F. Graziano, A. Ruzzo, O. Venditti, A. Onetti Muda, Alfredo Falcone, G. Tonini
Journal: Annals of Oncology (2009)
Drugs to Decrease Alcohol Consumption
Authors: Jan Koch-Weser, Edward M. Sellers, Claudio A. Naranjo, John E. Peachey
Journal: New England Journal of Medicine (1981)

MANY drugs have been used with the expectation of reducing alcohol consumption. A few seem to be associated with a reduction in alcohol use for up to three to six months in some patients, but none is associated with a reduction in alcohol consumption for longer periods.1 , 2 In spite of uncertainty about efficacy, over 90 per cent of physicians in private practice prescribe drugs for the treatment of alcoholism.3 The effectiveness of drug therapies for alcohol-related problems is seriously compromised by the difficulty of characterizing patients according to the cause of their alcohol problems, by the large number of nonpharmacologic . . .