tbuckley/cabot-search huggingface dataset:
Hungarian registers new and improved
Authors: G Jeremendy
Journal: BMJ (1994)

Rates of caesarean section, instrumental vaginal delivery, and breech presentation at Royal Infirmary, Glasgow, 1962-92 This has occurred alongside changes in obstetric practice, including changing rates of induction of labour and epidural analgesia and the introduction of antenatal and intrapartum care led by midwives.The largest group undergoing caesarean section comprises parous patients having an elective pro- cedure.Most are having repeat caesarean sections.If allowed to go into labour almost 70% would achieve a vaginal delivery; the remaining 30% might suffer a potentially traumatic caesarean section.This risk of an emergency caesarean section after a trial of labour may be unacceptable when compared with an elective procedure.Patient choice has become increasingly important.The morbidity after a caesarean section is often mentioned, but how does this compare with the morbidity after a traumatic vaginal delivery, whether spontaneous or instrumental?In 1962 in our hospital the most common indication for caesarean section was failure to progress in the first stage, closely followed by fetal distress.This remains the case 30 years later.Caesarean section for a breech presentation accounts for as little as 2 percentage points in the rate of caesarean section.We have surely heard enough opinion on the causes and problems of caesarean delivery and must not be confused by claims over "physiology."The Republic of Ireland advocates "active management" whereas the Netherlands advocates community obstetrics led by midwives, with low intervention rate.These arguments are contra- dictory, although both centres achieve a low rate of caesarean section.What we now require is information concerning the reasons for caesarean section.The problem should be addressed by the Royal College of Obstetricians and Gynaecologists at a national level.A Scottish study is under way to investigate the reasons for caesarean section.This should give information about different rates and may suggest ways of reducing these if this is thought to be desirable.We may conclude that a relatively high rate of caesarean section may be beneficial to the mother and her baby, and preferred.
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Authors: Esa R. Korpi, Bjørnar den Hollander, Usman Farooq, Elena Vashchinkina, Ramamoorthy Rajkumar, David J. Nutt, Petri Hyytiä, Gavin S. Dawe
Journal: Pharmacological Reviews (2015)

Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses.
Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors
Authors: W Gao, T McGarry, C Orr, J McCormick, D J Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2015)

Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA.To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA.Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA.Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10.This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA.
Suicide risk assessment and intervention in people with mental illness
Authors: J. M. Bolton, D. Gunnell, G. Turecki
Journal: BMJ (2015)

Suicide is the 15th most common cause of death worldwide. Although relatively uncommon in the general population, suicide rates are much higher in people with mental health problems. Clinicians often have to assess and manage suicide risk. Risk assessment is challenging for several reasons, not least because conventional approaches to risk assessment rely on patient self reporting and suicidal patients may wish to conceal their plans. Accurate methods of predicting suicide therefore remain elusive and are actively being studied. Novel approaches to risk assessment have shown promise, including empirically derived tools and implicit association tests. Service provision for suicidal patients is often substandard, particularly at times of highest need, such as after discharge from hospital or the emergency department. Although several drug based and psychotherapy based treatments exist, the best approaches to reducing the risk of suicide are still unclear. Some of the most compelling evidence supports long established treatments such as lithium and cognitive behavioral therapy. Emerging options include ketamine and internet based psychotherapies. This review summarizes the current science in suicide risk assessment and provides an overview of the interventions shown to reduce the risk of suicide, with a focus on the clinical management of people with mental disorders.
Early postoperative changes in regional systolic and diastolic left ventricular function after transmyocardial laser revascularization
Authors: G.Chad Hughes, Ashish S. Shah, Bangliang Yin, Ming Shu, Carolyn L. Donovan, Donald D. Glower, James E. Lowe, Kevin P. Landolfo
Journal: Journal of the American College of Cardiology (2000)
Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis
Authors: Halle R Amick, Gerald Gartlehner, Bradley N Gaynes, Catherine Forneris, Gary N Asher, Laura C Morgan, Emmanuel Coker-Schwimmer, Erin Boland, Linda J Lux, Susan Gaylord, Carla Bann, Christiane Barbara Pierl, Kathleen N Lohr
Journal: BMJ (2015)

<b>Study question</b> What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? <b>Methods</b> This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. <b>Summary answer and limitations</b> Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. <b>What this study adds </b>Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. <b>Funding, competing interests, data sharing</b> This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.
The contribution of Mycoplasma genitalium to the aetiology of sexually acquired infectious proctitis in men who have sex with men
Authors: M. Bissessor, S.N. Tabrizi, C.S. Bradshaw, C.K. Fairley, J.S. Hocking, S.M. Garland, J. Twin, M. Poljak, J. Peel, M.Y. Chen
Journal: Clinical Microbiology and Infection (2015)
Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)
Authors: Ebenezer Daniel, James Shaffer, Gui-shuang Ying, Juan E. Grunwald, Daniel F. Martin, Glenn J. Jaffe, Maureen G. Maguire
Journal: Ophthalmology (2015)
Genomic profiling of Sézary syndrome identifies alterations of key T cell signaling and differentiation genes
Authors: Linghua Wang, Xiao Ni, Kyle R Covington, Betty Y Yang, Jessica Shiu, Xiang Zhang, Liu Xi, Qingchang Meng, Timothy Langridge, Jennifer Drummond, Lawrence A Donehower, Harshavardhan Doddapaneni, Donna M Muzny, Richard A Gibbs, David A Wheeler, Madeleine Duvic
Journal: Nature Genetics (2015)
Testicular Cancer, Version 2.2015
Authors: Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Brian Shuch, Kanishka Sircar, Brad Somer, Richard B. Wilder, Mary Dwyer, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2015)

Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups--pure seminoma and nonseminoma--which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.
Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review
Authors: Eleonora Farina, Fabio Monari, Giovanni Tallini, Andrea Repaci, Renzo Mazzarotto, Francesca Giunchi, Riccardo Panzacchi, Silvia Cammelli, Gilbert D. A. Padula, Francesco Deodato, Renato Pasquali, Stefano Fanti, Michelangelo Fiorentino, Alessio G. Morganti
Journal: Endocrine Pathology (2015)
The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN)
Authors: Petra Baum, Joanna Kosacka, Irina Estrela-Lopis, Katrin Woidt, Heike Serke, Sabine Paeschke, Maximilian Stockinger, Nora Klöting, Matthias Blüher, Marco Dorn, Joseph Classen, Joachim Thiery, Ingo Bechmann, Klaus V. Toyka, Marcin Nowicki
Journal: Metabolism (2015)
Abstract 168: MALAT1 is crucial for epithelial-mesenchymal transition of breast cancer cells in acidic microenvironment
Authors: Subash C. Gupta, Yin-Yuan Mo
Journal: Cancer Research (2015)

Abstract Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is found up-regulated in several tumors. However, little is known about the role of MALAT1 in breast cancer, which is one of the highly invasive tumors among women worldwide. In this study, we found that MALAT1 was highly expressed in both breast cancer cell lines and breast cancer specimens in comparison to normal specimens. We found that low extracellular pH (pHe-acidosis), a major hallmark of solid tumors, further up-regulates MALAT-1 in several breast cancer cell lines in a time-dependent manner. Furthermore, acidosis induces epithelial to mesenchymal transition (EMT)-associated vimentin and Twist 1 expression but suppresses E-cadherin levels in breast cancer cells. Moreover, breast cancer cells under low pHe adopt stem-ness property as revealed by an increase in CD44+ and ESA+ population, mammosphere formation, and expression of OCT-4, SOX-2 and Nanog. Acidosis promotes translocation of β-catenin from cytoplasm to nucleus. The antisense oligonucleotides mediated gene silencing of MALAT-1 prevents acidosis induced nuclear translocation of β-catenin. This is in consistent with our previous finding that breast cancer cells cultured under low pHe exhibit an increased invasion activity. These results suggest that acidosis-induced MALAT-1 trigger an EMT program, leading to cell invasion and metastasis. Therefore, MALAT-1 represents a potential target for breast cancer therapy. Studies are underway to delineate the mechanistic association between MALAT-1, β-catenin, and EMT in acidic microenvironment. Citation Format: Subash C. Gupta, Yin-Yuan Mo. MALAT1 is crucial for epithelial-mesenchymal transition of breast cancer cells in acidic microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 168. doi:10.1158/1538-7445.AM2015-168
Metastatic status of sentinel lymph nodes in melanoma determined noninvasively with multispectral optoacoustic imaging
Authors: Ingo Stoffels, Stefan Morscher, Iris Helfrich, Uwe Hillen, Julia Leyh, Neal C. Burton, Thomas C. P. Sardella, Jing Claussen, Thorsten D. Poeppel, Hagen S. Bachmann, Alexander Roesch, Klaus Griewank, Dirk Schadendorf, Matthias Gunzer, Joachim Klode
Journal: Science Translational Medicine (2015)

Optoacoustic imaging strategies can be used to identify metastasis in excised lymph nodes and to determine SLN status in patients noninvasively.
How many doctors are referred for child protection work?
Authors: Leonard H P Williams
Journal: BMJ (2008)

Catto’s analysis (previous letter) in response to Wheatley’s open letter needs comment.1 He must accept that the GMC’s decision about Meadow was incorrect. The High Court overturned the GMC’s decision, stating that the GMC’s judgment “approached the irrational.” The Court of Appeal confirmed the High Court’s action.2 Perhaps Catto would like to state that …
Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs
Authors: Elisa Corsiero, Michele Bombardieri, Emanuela Carlotti, Federico Pratesi, William Robinson, Paola Migliorini, Costantino Pitzalis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Rheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated antigens with generation of anti-citrullinated peptide/proteins antibodies (ACPA). Currently, the nature and source of citrullinated antigens driving the humoral autoimmune response within synovial ectopic lymphoid structures (ELS) is a crucial unknown aspect of RA pathogenesis. Here we characterised the autoreactive B-cell response of lesional B cells isolated from ELS+RA synovium. <h3>Methods</h3> Single synovial tissue CD19+cells were Fluorescence Activated Cell Sorting (FACS)-sorted and V<sub>H</sub>/V<sub>L</sub> Ig genes cloned to generate recombinant monoclonal antibodies (rmAbs) from patients with ELS+/ACPA+RA. <h3>Results</h3> RA-rmAbs immunoreactivity analysis provided the following key findings: (1) in a chIP-based array containing 300 autoantigens and in a ‘citrullinome’ multiplex assay, a strong reactivity against citrullinated histones H2A/H2B (citH2A/H2B) was observed in ∼40% of RA-rmAbs, followed by cit-fibrinogen and cit-vimentin; (2) anti-citH2A/H2B-reactive RA-rmAbs (but not anti-citH2A/H2B negative) selectively recognised neutrophil extracellular traps (NETs) from peripheral blood and/or RA joint neutrophils; (3) anti-citH2A/citH2B and anti-NET immunobinding was dependent on affinity maturation and was completely abrogated following reversion of hypermutated IgV<sub>H</sub>/V<sub>L</sub> genes to germline sequences; (4) ELS+ (not ELS−) RA synovial tissues engrafted into Severe Combined ImmunoDeficiency (SCID) mice released human anti-citH2A/citH2B and anti-NET antibodies in association with the intra-graft expression of CXCL13 and lymphotoxin (LT)-β, two master regulators of ELS. <h3>Conclusion</h3> We provided novel evidence that B cells differentiated within synovial ELS in the RA joints frequent target deiminated proteins which could be generated during NETosis of RA synovial neutrophils including histones. Thus, NETs could represent a source of citrullinated antigens fuelling the ACPA autoimmune response within the RA synovium.
Gingival crevicular fluid as a source of biomarkers for periodontitis
Authors: Silvana P. Barros, Ray Williams, Steven Offenbacher, Thiago Morelli
Journal: Periodontology 2000 (2015)

In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in periodontal disease pathogenesis, the inflammatory mediator levels present in gingival crevicular fluid represent relevant risk indicators for disease activity. Considerable work has been carried out to identify the many different cytokine inflammatory pathways and microbial stimuli that are associated with periodontal disease pathogenesis. Now, 'omics' approaches aim to summarize how these pathways interact and probably converge to create critical inflammatory networks. More recently, gingival crevicular fluid metabolomics appears promising as an additional diagnostic method. Biofilm structure and the host inflammatory response to the microbial challenge may induce specific inflammatory signatures. Host genetics and epigenetics may also modulate microbial colonization, adding to the multiplicity of potential causal pathways. Omics analyses of gingival crevicular fluid, measuring microbial and host interactions in association with the onset and progression of periodontal diseases, still show the potential to expand the landscape for the discovery of diagnostic, prognostic and therapeutic markers.
Counteraction by Prolactin of Androgen-Induced Inhibition of Mammary Tumor Growth in Rats2
Authors: S. K. Quadri, G. S. Kledzik, Joseph Meites
Journal: JNCI Journal of the National Cancer Institute (1974)

We investigated whether growth of 7,12dimethylbenz[a]anthracene-induced mammary adenocarcinomas, inhibited by an androgen, dromostanolone propionate, could be overcome by daily injections of prolactin. Female Sprague-Dawley rats with established mammary tumors were injected subcutaneously (sc) daily for 3 weeks with corn oil (controls), 0.5 mg dromostanolone propionate (DP) in corn oil, 1.0 mg NIH ovine prolactin, or 0.5 mg DP and 1.0 mg prolactin. Mammary tumors in control rats showed an increase in mean tumor diameter (MTD) by 48.4% and in mean tumor number (MTN) by 66.5% by the end of the treatment period, whereas DP produced a decrease of 65.6% in total MTD and 60.6% in MTN/rat. Prolactin alone produced gains of 169.8% in total MTD and 248.2% in MTD/rat. Simultaneous treatment with DP and prolactin cempletely prevented mammary tumor inhibition and moderately increased MTD and MTN. Termination of treatment resulted in continued tumor growth in controls, only slight resumption of tumor growth in the previously DP-treated rats, regression of tumor size and number in rats previously given prolactin alone, and a reduction in tumor growth in rats given both DP and prolactin. These results indicate that DP exerts its antitumor effects by blocking the peripheral stimulatory action of prolactin on the mammary tumor tissue, and that exogenously administered prolactin can overcome this inhibitory action of DP.