tbuckley/cabot-search huggingface dataset:
Pelvic Inflammatory Disease
Authors: Lars Weström
Journal: JAMA (1991)

Today, over a century after the first report on the links between sexually transmitted diseases (STDs), adnexitis, and infertility in women, Noeggerath's finding has become a serious public health problem. The past decade's epidemic of STDs<sup>2</sup>has been accompanied by an epidemic of pelvic inflammatory disease (PID).<sup>3</sup>Trailing after the STD-PID epidemic have been epidemics of sequelae, such as infertility, chronic pain, and ectopic pregnancy.<sup>3</sup>These threats to the fecundity of millions of young women can and must be met. This theme issue ofThe Journalpresents modern thinking on PID and its sequelae, as well as research challenges for the future. Pelvic inflammatory disease as a major public health problem is illustrated by Aral and coauthors,<sup>4</sup>who report that one of 10 American women suffers from PID during their reproductive years. As calculated by Washington and Katz,<sup>5</sup>each year, 1 million US women seek
Time Course of Increased Airway Narrowing Caused by Inhibition of Deep Inspiration during Methacholine Challenge
Authors: GREGORY G. KING, BARBARA J. MOORE, CHUN Y. SEOW, PETER D. PARÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inhibition of deep inspiration (DI) enhances methacholine-induced airway narrowing in normal subjects. However, the time course over which excessive airway narrowing develops during inhibition of DI is not known. We hypothesized that the development of enhanced airway narrowing when DI is inhibited is time dependent. Ten normal volunteers (five males and five females) inhaled five doses of methacholine (16 mg/ml for 2 min) at 5-min intervals during an initial methacholine challenge. FEV1 was measured at baseline and after each dose. On four subsequent days, the subjects again inhaled two, three, four, or five doses, in random order, without DIs during the challenge. FEV1 was measured only at baseline and after the last dose. Baseline FEV1 was normal in all subjects. The maximal mean percent decrease in FEV1 after the initial challenge was 10 ± 1.5%, but was 28 ± 6.0% when DIs were inhibited throughout the five inhalations (p < 0.01). The difference in decrease in FEV1 between days with and without DI became significant after 10 min (three doses), and remained stable thereafter when the response plateaued. The reversal of airway narrowing after three DIs was incomplete after 15 min (four doses). In conclusion, the increased airway narrowing associated with inhibition of DI during airway smooth-muscle contraction occurs after 10 min in normal subjects, at which time the response plateaus. However, the ability of DI to reverse airway narrowing appears to diminish progressively.
Localized unilateral hyperhidrosis
Authors: P.C.M. KERKHOF, J.A.J.C. AREND, M.T. BOUSEMA, E. STOLZ
Journal: British Journal of Dermatology (1987)

A case of unilateral hyperhidrosis of the face is described. Measurements of the rate of evaporative water loss from other areas of the body, showed a marked left‐right difference in the sweating rate on the arms and on the legs which had not been suspected clinically. Unilateral hyperhidrosis is a rare and puzzling disorder. Possible neurological causes are discussed.
The relationship between clinical outcomes and medication adherence in difficult-to-control asthma: Table 1
Authors: Anna C Murphy, Amandine Proeschal, Christopher E Brightling, Andrew J Wardlaw, Ian Pavord, Peter Bradding, Ruth H Green
Journal: Thorax (2012)

Medication non-adherence and the clinical implications in difficult-to-control asthma were audited. Prescription issue data from 115 patients identified sub-optimal adherence (<80%) in 65% of patients on inhaled corticosteroids (ICS) or combined ICS/long-acting β2 agonist (LABA). In those using separate ICS and LABA, adherence to LABA (50%) was significantly better than to ICS (14.3%). Patients with sub-optimal ICS adherence had reduced FEV(1) and higher sputum eosinophil counts. Adherence ratio was an independent predictor of previous ventilation for acute severe asthma (p=0.008). The majority of patients with difficult-to-control asthma are non-adherent with their asthma medication. Non-adherence is correlated with poor clinical outcomes.
Sonic Hedgehog Is Required for Progenitor Cell Maintenance in Telencephalic Stem Cell Niches
Authors: Robert Machold, Shigemi Hayashi, Michael Rutlin, Mandar D. Muzumdar, Susana Nery, Joshua G. Corbin, Amel Gritli-Linde, Tammy Dellovade, Jeffery A. Porter, Lee L. Rubin, Henryk Dudek, Andrew P. McMahon, Gord Fishell
Journal: Neuron (2003)
Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer’s pathophysiology and susceptibility
Authors: Daniel Sevlever, Fanggeng Zou, Li Ma, Sebastian Carrasquillo, Michael G Crump, Oliver J Culley, Talisha A Hunter, Gina D Bisceglio, Linda Younkin, Mariet Allen, Minerva M Carrasquillo, Sigrid B Sando, Jan O Aasly, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Olivia Belbin
Journal: Molecular Neurodegeneration (2015)

Alzheimer's disease is a neurodegenerative disorder in which extracellular deposition of β-amyloid (Aβ) oligomers causes synaptic injury resulting in early memory loss, altered homeostasis, accumulation of hyperphosphorylated tau and cell death. Since proteins in the SNAP (Soluble N-ethylmaleimide-sensitive factor Attachment Protein) REceptors (SNARE) complex are essential for neuronal Aβ release at pre-synaptic terminals, we hypothesized that genetically controlled SNARE expression could alter neuronal Aß release at the synapse and hence play an early role in Alzheimer's pathophysiology.Here we report 5 polymorphisms in Vesicle-Associated Membrane Protein 1 (VAMP1), a gene encoding a member of the SNARE complex, associated with bidirectionally altered cerebellar VAMP1 transcript levels (all p<0.05). At the functional level, we demonstrated that control of VAMP1 expression by heterogeneous knockdown in mice resulted in up to 74% reduction in neuronal Aβ exocytosis (p<0.001). We performed a case-control association study of the 5 VAMP1 expression regulating polymorphisms in 4,667 Alzheimer's disease patients and 6,175 controls to determine their contribution to Alzheimer's disease risk. We found that polymorphisms associated with increased brain VAMP1 transcript levels conferred higher risk for Alzheimer's disease than those associated with lower VAMP1 transcript levels (p=0.03). Moreover, we also report a modest protective association for a common VAMP1 polymorphism with Alzheimer's disease risk (OR=0.88, p=0.03). This polymorphism was associated with decreased VAMP1 transcript levels (p=0.02) and was functionally active in a dual luciferase reporter gene assay (p<0.01).Genetically regulated VAMP1 expression in the brain may modify both Alzheimer's disease risk and may contribute to Alzheimer's pathophysiology.
<i>Intensity</i>; in-ten-si-ty;<i>noun</i>. 1. Often used ambiguously within resistance training. 2. Is it time to drop the term altogether?
Authors: James Steele
Journal: British Journal of Sports Medicine (2013)

Recently in BJSM , Dr Berkoff1 highlighted some ‘hot topics’ in sports and exercise medicine. A variety of topics were covered, all of which were ‘hot’. Of particular interest, however, was the fact that Dr Berkoff preceded his article with a definition of ‘hot’. Within sports and exercise medicine, and indeed in all scientific disciplines, definitions are of great importance. In fact, “The primary advantage of operational definitions lies in the unification of science and the resolution of controversy.”2 It is the definition and use of a term within a topic that might also be deemed as ‘hot’ that this editorial attempts to address: Intensity in resistance training (RT).

Recent publications regarding RT have attempted to offer clarification on the definition of intensity .3 ,4 Fisher and Smith3 wrote regarding the use of the term intensity within RT suggesting that it is better representative of effort , whereas other authors have considered it synonymous with load .4 Fisher and Smith2 are not the first to suggest that the use of intensity to refer to load in RT is inappropriate. Others have previously attempted to instigate a change in the language used by researchers and practitioners.5 ,6 Despite previously finding myself supporting this view (that intensity is better defined as effort and not load ) regarding the use of the term and having published as such,6 ,7 further consideration has left me doubting the value of both interpretation of intensity as synonymous with load or effort . Thus, this editorial seeks to ask the readers of BJSM , and the wider community involved in RT, to consider the use of the term intensity as it stands and whether both sides of the disagreement are defending inappropriate idioms. More specifically, however, it …
Hormonal treatment in advanced non-small cell lung cancer: fact or fiction?
Authors: JF Vansteenkiste, JP Simons, EF Wouters, MG Demedts
Journal: European Respiratory Journal (1996)

In patients with advanced non-small cell lung cancer, cachexia is an important cause of morbidity and mortality. The pathogenic mechanism of this finding, usually referred to as "cancer anorexia and cachexia syndrome" (CACS), is complex and far from completely understood, but a disturbed equilibrium between possible food intake and metabolic needs seems to be fundamental. The literature data on the treatment options in advanced non-small cell lung cancer (NSCLC) with cachexia are reviewed. Based on the clinical studies on cancer cachexia, some recommendations for the therapeutic approach of this disorder in patients with advanced NSCLC can be given. Metoclopramide is easily administered, can alleviate gastric disturbances, but probably does not correct the catabolic spiral of CACS. There are not enough data to advise the use of parenteral nutritional support, hydrazine, cyproheptadine, tetrahydrocannabinol or nandrolone decanoate. Corticosteroids are useful in additional analgesia and fast palliation of very weak and debilitated patients in the final episode of their disease. Recent data in non-small cell lung cancer patients are in favour of the use of high-dose progestagens to improve both appetite and weight.
The Genetics of Eating Disorders
Authors: Sara E. Trace, Jessica H. Baker, Eva Peñas-Lledó, Cynthia M. Bulik
Journal: Annual Review of Clinical Psychology (2013)

Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.
Resistance Emerges to Second-Generation Antiandrogens in Prostate Cancer
Authors: William G. Nelson, Srinivasan Yegnasubramanian
Journal: Cancer Discovery (2013)

Abstract Summary: The appearance of a mutant androgen receptor, ARF876L, in prostate cancer cells chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist to agonist receptor function, undermining the potential long-term effectiveness of these second-generation antiandrogen drugs. Cancer Discov; 3(9); 971–4. ©2013 AACR. See related article by Joseph et al., p. 1020 See related article by Korpal et al., p. 1030
PARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis
Authors: Kevin W. O'Connor, Donniphat Dejsuphong, Eunmi Park, Claudia M. Nicolae, Alec C. Kimmelman, Alan D. D'Andrea, George-Lucian Moldovan
Journal: Cancer Research (2013)

Treatment options for patients with pancreatic ductal adenocarcinoma (PDAC) remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here, we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell-cycle alterations associated with S-phase delay, perturbed DNA replication, and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat PDAC.
THE PRODUCTION OF ANTIPNEUMOCOCCIC SERUM
Authors: Rufus Cole, Henry F. Moore
Journal: The Journal of Experimental Medicine (1917)

In the production of immune serum for therapeutic purposes strict attention must be paid to the immunological specificity of the bacteria used for immunization. At present the only serum of which the therapeutic value has been proven is that effective against Type I pneumococcus infection. This serum should have agglutinating power for Type I pneumococcus and should have the power of protecting mice against large amounts of virulent culture. Experiments have shown that for producing the primary immunity most rapidly several series of small doses of dead cultures should be given, the injections being made daily for 6 to 7 days, followed by a week in which no injections are made. To produce the highest type of immunity probably living organisms are required. These should be given in moderate doses daily for 3 days, with an interval of a week between each series of injections. By following accurately the methods described, horses may be made to produce rapidly a high grade of specific serum. The observations so far made indicate the importance of employing small doses of culture frequently repeated in this form of immunization.
Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants
Authors: Florian Klein, Lilian Nogueira, Yoshiaki Nishimura, Ganesh Phad, Anthony P. West, Ariel Halper-Stromberg, Joshua A. Horwitz, Anna Gazumyan, Cassie Liu, Thomas R. Eisenreich, Clara Lehmann, Gerd Fätkenheuer, Constance Williams, Masashi Shingai, Malcolm A. Martin, Pamela J. Bjorkman, Michael S. Seaman, Susan Zolla-Pazner, Gunilla B. Karlsson Hedestam, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2014)

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian–human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.
Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF
Authors: Evelyn Fessler, Tijana Borovski, Jan Paul Medema
Journal: Molecular Cancer (2015)

Glioblastoma multiforme (GBM) is a rapidly growing malignant brain tumor, which has been reported to be organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. Recent studies demonstrate that this hierarchy does not follow a one-way route but can be reverted with more differentiated cells giving rise to cells possessing CSC features. We investigated the role of tumor microvascular endothelial cells (tMVECs) in reverting differentiated glioblastoma cells to CSC-like cells.We made use of primary GBM lines and tMVECs. To ensure differentiation, CSC-enriched cultures were forced into differentiation using several stimuli and cultures consisting solely of differentiated cells were obtained by sorting on the oligodendrocyte marker O4. Reversion to the CSC state was assessed phenotypically by CSC marker expression and functionally by evaluating clonogenic and multilineage differentiation potential.Conditioned medium of tMVECs was able to replenish the CSC pool by phenotypically and functionally reverting differentiated GBM cells to the CSC state. Basic fibroblast growth factor (bFGF), secreted by tMVECs, recapitulated the effects of the conditioned medium in inducing re-expression of CSC markers and increasing neurosphere formation ability of differentiated GBM cells.Our findings demonstrate that the CSC-based hierarchy displays a high level of plasticity showing that differentiated GBM cells can acquire CSC features when placed in the right environment. These results point to the need to intersect the elaborate network of tMVECs and GBM CSCs for efficient elimination of GBM CSCs.
OP21 * ASSESSING ASSOCIATED SYMPTOMS OF FATIGUE: TRIALLING A 'SYMPTOMS MDM' IN EDINBURGH FOR PRIMARY BRAIN TUMOUR
Authors: J. C. Day, B. Berntzen, A. Rooney, C. Derry, E. Caldwell, R. Rhia, R. Grant
Journal: Neuro-Oncology (2014)

INTRODUCTION: Fatigue is unusual daytime tiredness not relieved by sleep. It is common and with mixed aetiology in glioma. Annual fatigue assessment in stable patients with glioma is being trialled through a ‘symptoms MDM’ METHOD: Patients aged >18years, diagnosed with a glioma that was clinically stable, and had completed a fatigue study, were offered further clinical evaluation of their results by discussion at a ‘symptoms MDM’. This included a neurologist, clinical psychologist, psychiatrist and sleep consultant. Assessments included self-reported fatigue, mood, cognition, a growth hormone questionnaire, full neurological examination, and 2 week sleep assessment using an Actigraphy Watch and sleep log. RESULTS: 37/50 patients requested further assessment, including 10/10 severely fatigued, 22/24 moderately fatigued, 4/8 mildly fatigued and 1/8 non-fatigued. Of these the HADS depicted 20 patients with abnormal anxiety (8 borderline) and 5 with abnormal depression (11 borderline), 36 had poor cognition in one or more areas, and a sleep consultant reviewed 23 with abnormal sleep.Individual intervention plans included combinations of: referrals to clinical psychology (10), psychiatry (2), endocrinology (17), sleep clinic (5) and anti-epileptic medication review (9). Twelve were offered local support group in formation, and 24 were offered self-guided relaxation and sleep hygiene information. Almost all patients agreed to all interventions; 1 declined clinical psychology referral, 3 declined anti-epileptic review due to regaining a driving licence. CONCLUSION: Fatigue in glioma is common, complex and debilitating, but may be helped by managing symptoms, through annual ‘symptoms MDM’ and individualised treatment plans.
Abstract P264: Meeting <i>2008 Physical Activity Guidelines for Americans</i> Reduces Risk of Recurrent CVD Events in MI Survivors: The Western New York Acute MI Study (1996–2006)
Authors: Joan M Dorn, Kathleen Hovey, Maurizio Trevisan
Journal: Circulation (2012)

Introduction: The 2008 Physical Activity Guidelines for Americans (PAG) recommend adults perform at least 150 minutes/week of moderate intensity physical activity or 75 minutes/week of vigorous intensity activity or an equivalent combination of both in order to obtain important health benefits, including lower CHD risk. Despite advances in clinical medicine, survivors of MI remain at substantial risk of recurrent cardiovascular events and death. The aim of our prospective study was to examine whether meeting the PAG reduced risk of recurrent CVD events in MI patients. Hypothesis: We hypothesized that MI survivors who met the current PAG had a more favorable prognosis than those who did not meet the guidelines. Methods: Incident MI cases (933 men, 354 women, 35–69 years old) recruited from 12 of 15 Western NY hospitals completed an interviewer-administered survey and clinic exam. Physical activity (PA) in the previous seven days was assessed using the Stanford 7-day PA recall. Minutes reported in moderate and vigorous intensity recreational, household and occupational activity (MVPA) were summed and participants were categorized as follows (min/week): inactive (0), insufficiently active (&gt;0–&lt;150), met (150–300), and exceeded the guideline goal (&gt;300). Participant surveys, medical records and a search of the National Death Index Plus were used to determine fatal and non-fatal recurrent CVD (ICD9 390–450) events. Cox regression analysis adjusting for age (in years), gender, education (in years), race, BMI, smoking status, hypertension and use of diabetes and lipid medication was conducted to examine the association between PA and recurrent events. Results: During a mean follow up of 4.1 years, 301 recurrent CVD events occurred. At baseline, 174 (13.5%) participants reported no MVPA, 216 (16.8%) were insufficiently active, whereas 259 (20.1%) met and 638 (49.6%) exceeded the PAG, respectively. Multivariate adjusted hazard ratios (95% CI) for recurrent CVD events were Inactive [Ref (1.00)], insufficiently active [0.68 (0.46–1.01)], met [0.63 (0.43–0.92)], and exceeded the guideline goal [0.63 (0.45–0.87)], p-trend =0.019. Conclusion: In this prospective population-based study, there is evidence to support that meeting the 2008 Physical Activity Guidelines for Americans has significant benefits on fatal and non-fatal recurrent CVD events in men and women following myocardial infarction.
A prospective study of the radiological changes in the cervical spine in early rheumatoid disease.
Authors: J Winfield, D Cooke, A S Brook, M Corbett
Journal: Annals of the Rheumatic Diseases (1981)

The cervical spine radiographs of 100 patients with early rheumatoid disease were studied annually, on a prospective basis, for a mean follow-up period of 7 years 2 months. Atlantoaxial subluxation developed in 12 patients. The subluxation was more frequent in females, more severe in patients with progressive, seropositive, erosive rheumatoid disease, and more marked in patients treated with oral corticosteroids. Subaxial subluxation, affecting upper cervical disc levels, occurred in a further 20 patients. Three patients developed vertical subluxation. The mobility of the cervical spine affects the degree of subluxation achieved, and when assessing serial films for subluxation it may be necessary to measure the cervical spine flexion before deciding whether subluxation has progressed or not. Over 80% of the patients with subluxation developed the first evidence of subluxation within 2 years of disease onset. Subluxation in the cervical spine is not, therefore, a late complication of rheumatoid disease. During the follow-up period none of the patients developed neurological signs.
Cortistatin production by HepG2 human hepatocellular carcinoma cell line and distribution of somatostatin receptors
Authors: George Notas, George Kolios, Niki Mastrodimou, Marilena Kampa, Anna Vasilaki, Costas Xidakis, Elias Castanas, Kyriaki Thermos, Elias Kouroumalis
Journal: Journal of Hepatology (2004)