tbuckley/cabot-search huggingface dataset:
Europe the continent with the lowest fertility
Journal: Human Reproduction Update (2010)

Although fertility rates are falling in many countries, Europe is the continent with the lowest total fertility rate (TFR). This review assesses trends in fertility rates, explores possible health and social factors and reviews the impact of health and social interventions designed to increase fertility rates.Searches were done in medical and social science databases for the most recent evidence on relevant subject headings such as TFR, contraception, migration, employment policy and family benefits. Priorities, omissions and disagreements were resolved by discussion.The average TFR in Europe is down to 1.5 children per woman and the perceived ideal family size is also declining. This low fertility rate does not seem directly caused by contraception since in Northern and Western Europe the fertility decline started in the second half of the 1960s. Factors impacting on lower fertility include the instability of modern partnerships and value changes. Government support of assisted human reproduction is beneficial for families, but the effect on TFR is extremely small. Government policies that transfer cash to families for pregnancy and child support also have small effects on the TFR.Societal support for families and for couples trying to conceive improves the lives of families but makes no substantial contribution to increased fertility rates.
Alk Inhibitor Ap26113 in Patients with Advanced Malignancies, Including Alk+ Non-Small Cell Lung Cancer (Nsclc): Updated Efficacy and Safety Data
Authors: S. Gettinger, L. Bazhenova, R. Salgia, C. Langer, K. Gold, R. Rosell, A. Shaw, G.J. Weiss, N.I. Narasimhan, D.J. Dorer, V.M. Rivera, T. Clackson, F.G. Haluska, R. Camidge
Journal: Annals of Oncology (2014)
Percutaneous mitral commissurotomy for restenosis after surgical commissurotomy
Authors: Bernard Iung, Eric Garbarz, Pierre Michaud, Abdallah Mahdhaoui, Steeven Helou, Bruno Farah, Patricia Berdah, Pierre-Louis Michel, Yasuhiro Makita, Bertrand Cormier, Philippe Luxereau, Alec Vahanian
Journal: Journal of the American College of Cardiology (2000)
Improvement of physicochemical stability of highly-concentrated antibodies using cyclodextrin polypseudorotaxane hydrogels
Authors: Naoko Ohshita, Anna Tajima, Taishi Higashi, Keiichi Motoyama, Sawako Koyama, Ruriko Iibuchi, Shiuhei Mieda, Kenji Handa, Tomoaki Kimoto, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Determinants of Diabetes Remission and Glycemic Control After Bariatric Surgery
Authors: Simona Panunzi, Lena Carlsson, Andrea De Gaetano, Markku Peltonen, Toni Rice, Lars Sjöström, Geltrude Mingrone, John B. Dixon
Journal: Diabetes Care (2015)

Eligibility criteria for bariatric surgery in diabetes include BMI ≥35 kg/m(2) and poorly controlled glycemia. However, BMI does not predict diabetes remission, and thus, predictors need to be identified.Seven hundred twenty-seven patients were included in a database merged from the Swedish Obese Subjects (SOS) study and two randomized controlled studies, with 415 surgical and 312 medical patients in total. Bariatric operations were divided into gastric only (GO) and gastric plus diversion (GD).Sixty-four percent of patients in the surgical arm and 15.0% in the medical arm experienced diabetes remission (P < 0.001). GO yielded 60% remission, and GD yielded 76% remission. The best predictors of diabetes remission were lower baseline glycemia and shorter diabetes duration. However, when operation type was considered, GD predicted a higher likelihood of remission and greater weight loss. Patients in remission (responders) lost more weight (25% vs. 17%) and waist circumference (18% vs. 13%) and experienced better insulin sensitivity than nonresponders.Surgery is more effective than medical treatment in achieving diabetes remission and tighter glycemic control. Shorter diabetes duration, lower fasting glycemia before surgery, and GD versus GO procedures independently predict higher rates of remission, whereas baseline HbA1c and waist circumference predict improved glycemic control. The results show the advantage of an early operation together with better controlled glycemia on diabetes remission independently of BMI.
Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease
Authors: Steven E Reis, Richard Holubkov, Joon S Lee, Barry Sharaf, Nathaniel Reichek, William J Rogers, Edward G Walsh, Anthon R Fuisz, Richard Kerensky, Katherine M Detre, George Sopko, Carl J Pepine
Journal: Journal of the American College of Cardiology (1999)
Bone and joint changes in haemochromatosis.
Journal: BMJ (1969)

100l.)g.) min. 100ml.) (mg.) 100ml.) 100M~l. KAnt) (mg.) (mg.) (m. 1 + 220 1,800 125 3-7 610 9-8 39 105 118 2-6 6-6 2 + 220 930 6-9 2-9 390 9-5 3-1 23-0 150 2-8 6-3 3 + 290 1,920 4 0 3-5 560 10-8 3-2 15-0 65 3-3 6-2 4 0 60 0 0 5-5 620 10-2 2-8 9 0 252 7-0 99 5 + 230 715 8-2 2-8 760 9 9 3-1 13-0 384 30 8-8 6 0 180 1,520 7 0 6-6 500 9 2 3-0 12-0 41 2-5 7-1 7 + 60 100 1.0 4-5 610 10-6 4-3 17-0 113 8-3 13-2 8 + 40 54 10 4 5 450 9-2 2-3 42-0 428 2 6 5-9 9 220 - 64 4-1 480 100 3-3 25-0 51 19 4-6 10 0 170 376 - 4-7 400 10-0 2-3 7-5 269 8-4 11-0 11 + 220 950 2-9 - 10-7 4-8 13-0 - 1-6 152
Underlying Autoimmune Disease Is Not a Contraindication to the Use of Ipilimumab
Authors: Mary L. Disis
Journal: JAMA Oncology (2015)

Douglas B. Johnson, MD; Ryan J. Sullivan, MD; Patrick A. Ott, MD, PhD; Matteo S. Carlino, MBBS; Nikhil I. Khushalani, MD; Fei Ye, PhD; Alexander Guminski, MD, PhD; Igor Puzanov, MD; Donald P. Lawrence, MD; Elizabeth I. Buchbinder, MD; Tejaswi Mudigonda, BS; Kristen Spencer, DO; Carolin Bender, MD; Jenny Lee, MBBS; Howard L. Kaufman, MD; Alexander M. Menzies, MBBS; Jessica C. Hassel, MD; Janice M. Mehnert, MD; Jeffrey A. Sosman, MD; Georgina V. Long, MBBS; Joseph I. Clark, MD
Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia
Authors: Ravi Thadhani, Henning Hagmann, Wiebke Schaarschmidt, Bernhard Roth, Tuelay Cingoez, S. Ananth Karumanchi, Julia Wenger, Kathryn J. Lucchesi, Hector Tamez, Tom Lindner, Alexander Fridman, Ulrich Thome, Angela Kribs, Marco Danner, Stefanie Hamacher, Peter Mallmann, Holger Stepan, Thomas Benzing
Journal: Journal of the American Society of Nephrology (2015)

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20–38 years of age) with very preterm preeclampsia (23–32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%–28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2–11) and 15 days (range 11–21) in women treated once and multiple times, respectively, compared with 3 days (range 0–14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.
Identifying alcoholism in treated opiate addicts
Authors: B J Rounsaville, M M Weissman, C Wilber, H D Kleber
Journal: American Journal of Psychiatry (1983)

The authors evaluated the usefulness of the Michigan Alcoholism Screening Test in detecting alcoholism (as defined by the Research Diagnostic Criteria) in opiate addicts. The test was found to be adequately sensitive and specific in detecting current cases of alcoholism but inadequate for detecting alcoholic opiate addicts whose drinking was currently under control.
Cutaneous <scp>T</scp>‐cell lymphoma: 2016 update on diagnosis, risk‐stratification, and management
Authors: Ryan A. Wilcox
Journal: American Journal of Hematology (2015)

Disease overview : Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Diagnosis :The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk‐adapted therapy : TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers or histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. In highly‐selected patients, allogeneic stem‐cell transplantation may be considered, as this may be curative in some patients. Am. J. Hematol. 91:151–165, 2016. © 2015 Wiley Periodicals, Inc.
Transcatheter Versus Surgical Closure of Perimembranous Ventricular Septal Defects in Children
Authors: Jian Yang, Lifang Yang, Shiqiang Yu, Jincheng Liu, Jian Zuo, Wensheng Chen, Weixun Duan, Qijun Zheng, Xuezeng Xu, Jun Li, Jun Zhang, Jian Xu, Lijun Sun, Xiuling Yang, Lize Xiong, Dinghua Yi, Lei Wang, Qingchun Liu, Shuping Ge, Jun Ren
Journal: Journal of the American College of Cardiology (2014)

The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial.pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial.Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared.Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p < 0.001) in minor adverse events (32 vs. 7), quantity of blood transfused, duration of the procedure, median hospital stay, median intensive care unit stay, median hospitalization cost, and median blood loss. During a median follow-up of 2 years, the left ventricular end-diastolic dimension of both groups returned to normal and there was no difference in closure rate, adverse events, and complications between groups.Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799).
A Multicenter, Randomized, Open-Label Trial Evaluating Deferasirox Compared with Deferoxamine for the Removal of Cardiac Iron in Patients with β-Thalassemia Major and Iron Overload (CORDELIA).
Authors: Dudley J Pennell, John B Porter, Antonio Piga, Yongrong Lai, Amal El-Beshlawy, Khawla Beloul, Mohsen Elalfy, Akif Yesilipek, Yurdanur Kilinç, Tomasz Lawniczek, Dany Habr, Marianne Weisskopf, Yiyun Zhang, Yesim Aydinok
Journal: Blood (2012)
A Two-Step Pretargeted Nanotherapy for CD20 Crosslinking May Achieve Superior Anti-Lymphoma Efficacy to Rituximab
Authors: Te-Wei Chu, Rui Zhang, Jiyuan Yang, Mark P. Chao, Paul J. Shami, Jindřich Kopeček
Journal: Theranostics (2015)

The use of rituximab, an anti-CD20 mAb, in combination with chemotherapy is the current standard for the treatment of B-cell lymphomas.However, because of a significant number of treatment failures, there is a demand for new, improved therapeutics.Here, we designed a nanomedicine that crosslinks CD20 and directly induces apoptosis of B-cells without the need for toxins or immune effector functions.The therapeutic system comprises a pretargeting component (anti-CD20 Fab' conjugated with an oligonucleotide1) and a crosslinking component (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple complementary oligonucleotide2).Consecutive treatment with the two components resulted in CD20 clustering on the cell surface and effectively killed malignant B-cells in vivo.To enhance therapeutic efficacy, a two-step pretargeting approach was employed.We showed that the time lag between the two doses can be optimized based on pharmacokinetics and biodistribution of the Fab'-oligonucleotide1 conjugate.In a mouse model of human non-Hodgkin lymphoma (NHL), increasing the time lag from 1 h to 5 h resulted in dramatically improved tumor growth inhibition and animal survival.When the 5 h interval was used, the nanotherapy was more efficacious than rituximab and led to complete eradication of lymphoma cells with no signs of metastasis or disease recurrence.We further evaluated the nanomedicine using patient mantle cell lymphoma cells; the treatment demonstrated more potent apoptosis-inducing activity than rituximab hyper-crosslinked with secondary antibodies.In summary, our approach may constitute a novel treatment for NHL and other B-cell malignancies with significant advantages over conventional chemo-immunotherapy.
Adverse effects of antiparkinson drug withdrawal
Authors: T Jellinek, G Gardos, J O Cole
Journal: American Journal of Psychiatry (1981)

The authors conducted a double-blind, controlled study to test the behavioral, affective, and neurological effects of antiparkinson drug discontinuation. Patients were evaluated at baseline and at 2 and 4 weeks. Of 24 placebo patients 9 left the study early because of adverse effects; none of the 8 patients in the antiparkinsonian group did so. The placebo group had significantly more lower extremity movements, motor agitation, hallucinations, and physical complaints at 2 weeks and scored significantly higher in depression at 4 weeks. A sizable proportion of chronic, drug-treated schizophrenic patients appear to need antiparkinsonians for clinical stability.
Breakthrough candidaemia in the era of broad-spectrum antifungal therapies
Authors: G. Cuervo, C. Garcia-Vidal, M. Nucci, F. Puchades, M. Fernández-Ruiz, M. Obed, A. Manzur, C. Gudiol, J. Pemán, J.M. Aguado, J. Ayats, J. Carratalà
Journal: Clinical Microbiology and Infection (2015)
Une épidémie de légionellose parmi les visiteurs d'un salon en Belgique, 1999
Authors: K De Schrijver, E van Bouwel, L Mortelmans, P van Rossom, T De Beukelaer, C Vael, K Dirven, H Goossens, M Leven, O Ronveaux
Journal: Eurosurveillance (2000)

En novembre 1999, 93 cas de legionellose ont ete identifies au cours d’une epidemie associee a un salon a Kapellen, en Belgique (43 cas confirmes, 12 presumes et 38 possibles/cliniques). Cinq malades sont decedes. L’investigation epidemiologique a montre une association entre le temps passe au salon, l’exposition a certaines zones du chapiteau et la survenue de la maladie. Les analyses par PCR (polymerase chain reaction) ont montre qu’un bassin et une fontaine etaient contamines par Legionella.
Leading tobacco firm is accused of bribery
Authors: Adrian O’Dowd
Journal: BMJ (2015)

One of the world’s major tobacco companies, British American Tobacco (BAT), has been accused of repeated bribery by the BBC’s Panorama investigative programme. The London based company has, however, strongly rejected the claims, saying that the sources of the programme’s information were unreliable and that, as a firm, it would never tolerate corruption.

In the programme, screened on 30 November, investigators said that they had found evidence that the company had bribed civil servants and senior politicians in various African countries to damage rival companies, corrupt parliaments, and undermine a World Health Organization initiative against smoking.

The programme (www.bbc.co.uk/programmes/b006t14n) spoke to the whistleblower Paul Hopkins, a former employee who worked for BAT in Kenya for 13 …
Measuring the breathless brain: is real life too noisy?
Authors: Andrew Binks
Journal: European Respiratory Journal (2015)

The first brain study of “real-life” dyspnoea is limited by real-life, but gives us a renewed sense of direction <http://ow.ly/T70dp> In our 15-year history of mapping the central neural mechanisms of dyspnoea, we have discovered the complexities of obtaining an objective measure of the sensation and begun discriminating the emotional, cognitive and behavioural responses to it. The task has been complicated by use of a variety of laboratory models that likely produce varying forms of dyspnoea. There are at least three neurally distinct forms (air hunger, effort to breathe and chest tightness [1]) and each form has quantitatively, and maybe qualitatively, different affective components [2]. The stimuli used to gain the first insights into the “breathless brain” were tidal volume restriction [3], hypercapnia [4] and resistance loaded breathing [5]. The most consistent finding in these and subsequent studies [6–8] is activation of the insula cortex; a region also involved with the perception of other homeostatic warning signals such as pain, hunger and thirst [9]. The involvement (or not) of other brain regions has varied between studies and likely reflects the variety of stimuli and types of dyspnoea they generated. The most consistent factor throughout these studies is the use of healthy individuals as subjects.
Development of Th17‐Associated Interstitial Kidney Inflammation in Lupus‐Prone Mice Lacking the Gene Encoding STAT‐1
Authors: Gloria Yiu, Tue K. Rasmussen, Bahareh Ajami, David J. Haddon, Alvina D. Chu, Stephanie Tangsombatvisit, Winston A. Haynes, Vivian Diep, Larry Steinman, James Faix, Paul J. Utz
Journal: Arthritis & Rheumatology (2015)

Objective Type I interferon (IFN) signaling is a central pathogenic pathway in systemic lupus erythematosus (SLE), and therapeutics targeting type I IFN signaling are in development. Multiple proteins with overlapping functions play a role in IFN signaling, but the signaling events downstream of receptor engagement are unclear. This study was undertaken to investigate the roles of the type I and type II IFN signaling components IFN‐α/β/ω receptor 2 (IFNAR‐2), IFN regulatory factor 9 (IRF‐9), and STAT‐1 in a mouse model of SLE. Methods We used immunohistochemical staining and highly multiplexed assays to characterize pathologic changes in histology, autoantibody production, cytokine/chemokine profiles, and STAT phosphorylation in order to investigate the individual roles of IFNAR‐2, IRF‐9, and STAT‐1 in MRL/ lpr mice. Results We found that STAT‐1 −/− mice, but not IRF‐9 −/− or IFNAR‐2 −/− mice, developed interstitial nephritis characterized by infiltration with retinoic acid receptor–related orphan nuclear receptor γt–positive lymphocytes, macrophages, and eosinophils. Despite pronounced interstitial kidney disease and abnormal kidney function, STAT‐1 −/− mice had decreased proteinuria, glomerulonephritis, and autoantibody production. Phosphospecific flow cytometry revealed shunting of STAT phosphorylation from STAT‐1 to STAT‐3/4. Conclusion We describe unique contributions of STAT‐1 to pathology in different kidney compartments in a mouse model, and provide potentially novel insight into tubulointerstitial nephritis, a poorly understood complication that predicts end‐stage kidney disease in SLE patients.
Hyaluronan-CD44 interaction with neural wiskott-aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to β-catenin nuclear translocation, transcriptional upregulation and cell migration in ovarian tumor cells
Authors: Lilly Bourguignon, Karine Peyrollier, Eli Gilad, Amy Brightman
Journal: Cancer Research (2007)

2527   In this study we have investigated the interaction of hyaluronan (HA) and CD44 with the Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) in regulating actin polymerization and ErbB2/β-catenin signaling in human ovarian tumor cells (SK-OV-3.ipl cells). Biochemical and immunological analyses indicate that N-WASP is expressed in SK-OV-3.ipl cells and that the binding of HA stimulates N-WASP association with CD44 and Arp2/Arp3 leading to filamentous actin (F-actin) formation and ovarian tumor cell migration. In addition, HA binding promotes CD44-N-WASP association with ErbB2 and activates ErbB2 kinase activity which, in turn, increases phosphorylation of the cytoskeletal protein, β-catenin. Subsequently, phosphorylated β-catenin is transported into the nucleus leading to β-catenin-mediated TCF/LEF-transcriptional co-activation. Since HA-induced β-catenin phosphorylation, nuclear translocation and TCF/LEF transcriptional activation is effectively blocked by the ErbB2 inhibitor, AG825, we conclude that HA/CD44-N-WASP-associated ErbB2 activation is required for β-catenin-mediated signaling events.  In assessing the regulatory role of N-WASP in HA-CD44 signaling and ErbB2 activation, we have determined that overexpression of a dominant-negative N-WASP mutant protein [by transfecting cells with N-WASP’s VCA (verpolin homology, cofilin homology, and acidic domain) fragment cDNA] not only blocks HA/CD44-induced N-WASP-Arp2/3 complex formation, but also inhibits actin polymerization/F-actin formation and tumor cell migration. Transfection of SK-OV-3.ipl cells with N-WASP-VCAcDNA also significantly reduces HA-induced ErbB2 recruitment to CD44, diminishes β-catenin phosphorylation/nuclear translocation and abrogates TCF/LEF-specific transcriptional co-activation by β-catenin. Taken together, our findings strongly suggest that N-WASP plays a pivotal role in regulating HA-mediated CD44-ErbB2 interaction, β-catenin signaling and actin cytoskeleton functions that are required for tumor-specific behaviors (e.g. transcriptional upregulation and tumor cell migration) and ovarian cancer progression.
Fas expression in memory CD8+ T cell subsets augments cellular differentiation and effector function
Authors: Tori Yamamoto, Anthony Leonardi, Hui Liu, Ena Wang, Luca Gattinoni, Anthony Cruz, Claudia Ouyang, Richard Siegel, Nicholas Restifo, Christopher A Klebanoff
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Memory CD8+ T cells (TMem) have the capacity to provide lifelong host protection against intracellular pathogens and cancer. Despite phenotypic and functional heterogeneity among TMem, the expression of Fas — a tumor necrosis family receptor (TNFR) superfamily member