tbuckley/cabot-search huggingface dataset:
Level of Systolic Blood Pressure Within the Normal Range and Risk of Recurrent Stroke
Authors: Bruce Ovbiagele, Hans-Christophe Diener, Salim Yusuf, Reneé H. Martin, Daniel Cotton, Richard Vinisko, Geoffrey A. Donnan, Philip M. Bath, for the PROFESS Investigators
Journal: JAMA (2011)

Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear.To assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke.Post hoc observational analysis of a multicenter trial involving 20,330 patients (age ≥50 years) with recent non-cardioembolic ischemic stroke; patients were recruited from 695 centers in 35 countries from September 2003 through July 2006 and followed up for 2.5 years (follow-up ended on February 8, 2008). Patients were categorized based on their mean SBP level: very low-normal (<120 mm Hg), low-normal (120-<130 mm Hg), high-normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (≥150 mm Hg).The primary outcome was first recurrence of stroke of any type and the secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes.The recurrent stroke rates were 8.0% (95% CI, 6.8%-9.2%) for the very low-normal SBP level group, 7.2% (95% CI, 6.4%-8.0%) for the low-normal SBP group, 6.8% (95% CI, 6.1%-7.4%) for the high-normal SBP group, 8.7% (95% CI, 7.9%-9.5%) for the high SBP group, and 14.1% (95% CI, 13.0%-15.2%) for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low-normal SBP group (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.07-1.56), in the high SBP group (AHR, 1.23; 95% CI, 1.07-1.41), and in the very high SBP group (AHR, 2.08; 95% CI, 1.83-2.37). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low-normal SBP group (AHR, 1.31; 95% CI, 1.13-1.52), in the low-normal SBP group (AHR, 1.16; 95% CI, 1.03-1.31), in the high SBP group (AHR, 1.24; 95% CI, 1.11-1.39), and in the very high SBP group (AHR, 1.94; 95% CI, 1.74-2.16).Among patients with recent non-cardioembolic ischemic stroke, SBP levels during follow-up in the very low-normal (<120 mm Hg), high (140-<150 mm Hg), or very high (≥150 mm Hg) range were associated with increased risk of recurrent stroke.clinicaltrials.gov Identifier: NCT00153062.
Dietary Phytoestrogens and Lung Cancer Risk
Authors: Matthew B. Schabath, Ladia M. Hernandez, Xifeng Wu, Patricia C. Pillow, Margaret R. Spitz
Journal: JAMA (2005)

Despite lung-specific in vitro and in vivo studies that support a chemopreventive role for phytoestrogens, there has been little epidemiologic research focused on dietary intake of phytoestrogens and risk of lung cancer.To examine the relationship between dietary intake of phytoestrogens and risk of lung cancer.Ongoing US case-control study of 1674 patients with lung cancer (cases) and 1735 matched healthy controls. From July 1995 through October 2003, participants were personally interviewed with epidemiologic and food frequency questionnaires to collect demographic information and to quantify dietary intake of 12 individual phytoestrogens.Risk of lung cancer, estimated using unconditional multivariable logistic regression analyses stratified by sex and smoking status and adjusted for established and putative lung cancer risk factors.Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.64-0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42-0.70; P<.001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56-1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41-0.76; P<.001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46-0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31-0.68; P = .04 for interaction) reduction in risk of lung cancer.While there are limitations and concerns regarding case-control studies of diet and cancer, these data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer. Confirmation of these findings is still required in large-scale, hypothesis-driven, prospective studies.
Local Renal Circadian Clocks Control Fluid–Electrolyte Homeostasis and BP
Authors: Natsuko Tokonami, David Mordasini, Sylvain Pradervand, Gabriel Centeno, Céline Jouffe, Marc Maillard, Olivier Bonny, Frédéric Gachon, R Ariel Gomez, Maria Luisa S Sequeira-Lopez, Dmitri Firsov
Journal: Journal of the American Society of Nephrology (2014)

The circadian timing system is critically involved in the maintenance of fluid and electrolyte balance and BP control. However, the role of peripheral circadian clocks in these homeostatic mechanisms remains unknown. We addressed this question in a mouse model carrying a conditional allele of the circadian clock gene Bmal1 and expressing Cre recombinase under the endogenous Renin promoter (Bmal1(lox/lox)/Ren1(d)Cre mice). Analysis of Bmal1(lox/lox)/Ren1(d)Cre mice showed that the floxed Bmal1 allele was excised in the kidney. In the kidney, BMAL1 protein expression was absent in the renin-secreting granular cells of the juxtaglomerular apparatus and the collecting duct. A partial reduction of BMAL1 expression was observed in the medullary thick ascending limb. Functional analyses showed that Bmal1(lox/lox)/Ren1(d)Cre mice exhibited multiple abnormalities, including increased urine volume, changes in the circadian rhythm of urinary sodium excretion, increased GFR, and significantly reduced plasma aldosterone levels. These changes were accompanied by a reduction in BP. These results show that local renal circadian clocks control body fluid and BP homeostasis.
The role of mentoring in academic career progression: a cross-sectional survey of the Academy of Medical Sciences mentoring scheme
Authors: Amy C Iversen, Nigel AJ Eady, Simon C Wessely
Journal: Journal of the Royal Society of Medicine (2014)

Summary Objectives To describe a successful mentoring scheme designed for mid-career clinician scientists and to examine factors associated with mentee report of positive career impact. Design Mixed methods study including in-depth interviews and cross-sectional data collection via an online survey. Setting Academy of Medical Sciences mentoring scheme set up in 2002 and evaluated in 2010. Participants One hundred and forty-seven of 227 mentees took part in the study (response rate of 65%). Ten mentees, three mentors and eight stakeholders/scheme staff were selected to participate in in-depth interviews. Main outcome measures Qualitative data: Interviews were transcribed, and free text was analysed to identify themes and subthemes in the narrative. Quantitative data: We examined the associations of reported positive career impact of mentoring by performing simple and multiple logistic regression analysis. Results Mentoring success was determined by a variety of factors including reasons for selection (e.g. presence of a personal recommendation), mentee characteristics (e.g. younger age), experience and skills of the mentor (e.g. ‘mentor helped me to find my own solutions’) and the quality of the relationship (e.g. ‘my mentor and I set out clear expectations early on’). Conclusions Our evaluation demonstrates that both mentor and mentee value mentoring and that careful planning of a scheme including preparation, training and ongoing support of both mentor and mentee addressing expectations, building rapport and logistics are likely to be helpful in ensuring success and benefit from the intervention.
Skin problems associated with multifunctional acrylic monomers in ultraviolet curing inks
Authors: JAMES R. NETHERCOTT
Journal: British Journal of Dermatology (1978)

Fifteen cases of contact dermatitis and three of irritant contact conjunctivitis due to multifunctional acrylic monomers in printing inks are described. Seven with dermatitis were sensitized to pentaerythritol triacrylate but evidenced no cross-reactivity to methyl methacrylate. The other eight cases of dermatitis were irritant. Pentaerythritol triacrylate has been shown experimentally to be a cutaneous sensitizer for guinea-pigs and man. Multi-functional acrylates should be handled with minimal skin contact, to avoid cutaneous problems.
Surgery for Combined Valvular and Coronary Heart Disease
Authors: Floyd D. Loop
Journal: JAMA (1972)

Valvular heart disease, regardless of its etiology or chronicity, offers no protection against coronary atherosclerosis. Fifty patients with combined valve and coronary heart disease required aortocoronary bypass grafts in addition to valve reconstruction or replacement. The operative mortality was 8%. Twenty-three of 27 patients for whom follow-up has been more than six months after surgery (average: 14.8 months) are active or have returned to work. Only one patient experiences angina pectoris postoperatively and no myocardial infarctions have occurred in the late period. Eighteen patients underwent a second cardiac catheterization after an average interval of nine months and 24 of 26 grafts (92%) are patent. This review emphasizes the necessity for cinecoronary arteriography in the preoperative evaluation of valvular heart disease.
Treating and Preventing Adolescent Mental Health Disorders: What We Know and What We Don’t Know, A Research Agenda for Improving the Mental Health of Our Youthedited by Dwight L. Evans, Edna B. Foa, Raquel E. Gur, Herbert Hendin, Charles P. O’Brien, Martin E. P. Seligman, and B. Timothy Walsh. New York, Oxford University Press, 2005, 864 pp., $59.50.
Authors: ROBERT STERN
Journal: American Journal of Psychiatry (2007)
Cystin Localizes to Primary Cilia via Membrane Microdomains and a Targeting Motif
Authors: Binli Tao, Su Bu, Zhihua Yang, Brian Siroky, John C. Kappes, Andreas Kispert, Lisa M. Guay-Woodford
Journal: Journal of the American Society of Nephrology (2009)

Primary cilia are dynamic, complex structures that contain >500 proteins, including several related to polycystic kidney disease. How these proteins target to cilia and assemble is unknown. We previously identified Cys1 as the gene responsible for disease in Cys1(cpk) mice, a mouse model of autosomal recessive polycystic kidney disease; this gene encodes cystin, a 145-amino acid cilium-associated protein. Here, we characterized the localization of cystin in the embryonic kidney and liver, in isolated renal collecting ducts, and in an inner medullary collecting duct mouse cell line. Because endogenous levels of cystin expression are low, we generated inner medullary collecting duct cell lines that stably express enhanced green fluorescence protein-tagged constructs of wild-type cystin or various truncation mutants. We determined that cystin is myristoylated at its G2 residue and that N-myristoylated cystin fractionates with membrane microdomains. Furthermore, the N-myristoylation signal is necessary but not sufficient to target cystin to the primary cilium. Analysis of deletion and chimeric constructs identified an AxEGG motif that is necessary to target and retain cystin in the cilium. Derangement of these localization motifs may lead to cystic kidney disease.
Reaction Due To Milk Proteins Contaminating Lactose Added To Inhaled Corticosteroid
Authors: A.B. Sa, L.C.L. Oliveira, K.V.M. Miyagi, Y.A.M.F. Mello, E.C. Cabral, A.P.E. Carvalho, F.F. Komaroff, R.F.F. Gonçalves
Journal: Journal of Allergy and Clinical Immunology (2011)
Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the distal interphalangeal finger joints
Authors: D Santilli
Journal: Annals of the Rheumatic Diseases (2002)

Background: Multicentric reticulohistiocytosis (MRH) is a rare systemic disease, presenting with typical skin abnormalities and erosive polyarthritis, which is often associated with malignancy. Case report: A case of MRH arthropathy, in which the typical nodular skin manifestation of the disease was absent, is described in a patient with a past history of breast cancer and no evidence of recurrent or new malignancy. Results: Careful clinical and roentgenological evaluation disclosed important clues to differentiate this condition from other more common distal interphalangeal arthritides—namely, osteoarthritis and its "erosive" variant, rheumatoid arthritis, psoriatic arthritis, tophaceous gout, dialysis related hand arthropathy, and from the rarer fibroblastic rheumatism, all of which can be mimicked by MRH. Histopathology showed the characteristic histiocytic and multinucleated giant cell infiltrate with ground glass cytoplasm, and immunohistochemical analysis showed markers evocative of a monocyte/macrophage origin of MRH.
Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.
Authors: J L Speyer, U Beller, N Colombo, J Sorich, J C Wernz, H Hochster, M Green, R Porges, F M Muggia, R Canetta
Journal: Journal of Clinical Oncology (1990)

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.
A Simple and Portable Spray Pump for Disinfection
Authors: W. L. Mackenzie
Journal: BMJ (1901)

the impairment caused by the adenoids as was thus immediately removed by the operation could not have been de- pendent upon diminished intratympanic air tension depression of %the membrane and consequent depression of the ossicles; owing to the perforation of the membrane these factors would not be affected by the operation and it is evident that another cause is at work.The foregoing is part of a paper which in addition contained a criticism of the stenosal theory and a statement of con- siderations which might be useful when seeking an explana- tion of the difficulties which had been raised.Mr. JOBSoN HORNE said it was still within his recollection, and no doubt within that of others present, that discussion on a similar paper had taken place last year in the section at Ipswich.On that occasion he, together with others, expressed the opinion that the immediate improvement in hearing was in all probability due in a great measure to the sudden local depletion following the operation.It seemed to him that the present discussion had come round to the point where they left off last year, and that no material advance had been made in the elucidation of the problem.
Identifying the Best Candidate for Radical Prostatectomy Among Patients with High-Risk Prostate Cancer
Authors: Alberto Briganti, Steven Joniau, Paolo Gontero, Firas Abdollah, Niccolò M. Passoni, Bertrand Tombal, Giansilvio Marchioro, Burkhard Kneitz, Jochen Walz, Detlef Frohneberg, Chris H. Bangma, Markus Graefen, Alessandro Tizzani, Bruno Frea, R. Jeffrey Karnes, Francesco Montorsi, Hein Van Poppel, Martin Spahn
Journal: European Urology (2011)
Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin
Authors: Ronit Satchi-Fainaro, Roni Mamluk, Ling Wang, Sarah M. Short, Janice A. Nagy, Dian Feng, Ann M. Dvorak, Harold F. Dvorak, Mark Puder, Debabrata Mukhopadhyay, Judah Folkman
Journal: Cancer Cell (2005)
Endocrine Pacemaker for Complete Heart Block
Authors: Judah Folkman, L. Henry Edmunds
Journal: Circulation Research (1962)

In dogs with complete heart block, adrenal medulla or thyroid autografts, or tri-idiothyronine tablets implanted into the myocardium produced a sustained elevation in heart rate for 24 to 96 hours. Exercise of the animal caused a further increase in heart rate. Electrocardiographic studies suggested that the faster pacemaker activity originated from the area of implantation of the grafts or the tablets. After implantation of either thyroid grafts or tri-iodothyronine tablets, a latent period of 8 to 12 hours occurred before the new pacemaker became active. Data suggest that the pacemaker shift and the increase in heart rate are due to a local increase in hormones provided by the autografts or by the tri-iodothyronine tablets. There was no effect on the heart rate when similar or higher doses of tri-iodothyronine were given systemically. The method of tri-iodothyronine implantation into the myocardium is valuable in the study of the action of this hormone. The technique has two unique advantages: the reaction remains localized, and the endpoint is signaled electrically. Reserpine suppresses the ability of implanted tri-iodothyronine to increase the heart rate. This suggests that normal catecholamine levels are required for the positive chronotropic action of tri-iodothyronine. Myocardial catecholamine concentrations were not increased around the implanted tri-iodothyronine tablets. If catecholamines are necessary for the action of tri-iodothyronine on the myocardium, this suggests that tri-iodothyronine causes sensitization of the myocardium to the catecholamines, rather than causing an accumulation of the catecholamines themselves. Fibrous encapsulation of endocrine transplants appears to prevent permanent pacemaker activity. In lieu of successful thyroid transplants, myocardial implantations of tri-iodothyronine as slow release pellets are potentially applicable for patients with complete heart block.
American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Reduction
Authors: Kala Visvanathan, Rowan T. Chlebowski, Patricia Hurley, Nananda F. Col, Mary Ropka, Deborah Collyar, Monica Morrow, Carolyn Runowicz, Kathleen I. Pritchard, Karen Hagerty, Banu Arun, Judy Garber, Victor G. Vogel, James L. Wade, Powel Brown, Jack Cuzick, Barnett S. Kramer, Scott M. Lippman
Journal: Journal of Clinical Oncology (2009)

Purpose To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. Methods A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) –positive invasive tumors. Women ≤ 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.
Neanderthal Introgression at Chromosome 3p21.31 Was Under Positive Natural Selection in East Asians
Authors: Qiliang Ding, Ya Hu, Shuhua Xu, Jiucun Wang, Li Jin
Journal: Molecular Biology and Evolution (2013)

Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin introgression in Eurasians. Here, we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans. We also detected a signal of strong positive selection in this region only in East Asians. Our data indicate that likely candidate targets of selection include rs12488302-T and its associated alleles—among which four are nonsynonymous, including rs35455589-G in HYAL2, a gene related to the cellular response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly, the distribution of rs35455589-G suggests that this allele was lost during the exodus of ancestors of modern Eurasians from Africa and reintroduced to Eurasians from Neanderthals.
Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin
Authors: A. Zaanan, P. Cuilliere-Dartigues, A. Guilloux, Y. Parc, C. Louvet, A. de Gramont, E. Tiret, S. Dumont, B. Gayet, P. Validire, J.-F. Fléjou, A. Duval, F. Praz
Journal: Annals of Oncology (2009)
Outbreak of calicivirus gastroenteritis associated with eating frozen raspberries
Authors: A Pönka, L Maunula, C. H. von Bonsdorff, O Lyytikaïnen
Journal: Eurosurveillance (1999)

Small round structured viruses (SRSVs - for example, calici-, astro-, and entero-viruses) are the commonest causes of outbreaks of non-bacterial gastroenteritis worldwide. Transmission of SRSVs by water and by various foods – including salads, bakery prod