tbuckley/cabot-search huggingface dataset:
Stimulus Specific Responses from Beyond the Classical Receptive Field: Neurophysiological Mechanisms for Local-Global Comparisons in Visual Neurons
Authors: John Allman, Francis Miezin, EveLynn McGuinness
Journal: Annual Review of Neuroscience (1985)

We perceive the visual world as a unitary whole, yet one of the guiding principles of nearly a half century of neurophysiological research since the early recordings by Hartline (1938) has been that the visual system consists of neurons that are driven by stimulation within small discrete portions of the total visual field. These classical receptive fields (CRFs) have been mapped with the excitatory responses evoked by a flashed or moving stimulus, usually a spot or bar of light. Most of the visual neurons, in turn, are organized in a series of maps of the visual field, at least 10 of which exist in the visual cortex in primates as well as additional topographic representations in the lateral geniculate body, pulvinar and optic tectum (Allman 1977, Newsome & Allman 1980, Allman & Kaas 1984). It has been widely assumed that perceptual functions that require the integration of inputs over large portions of the visual field must be either collective properties of arrays of neurons representing the visual field, or features of those neurons at the highest processing levels in the visual system, such as the cells in inferotemporal or posterior parietal cortex that typically possess very large receptive fields and do not appear to be organized in visuotopic maps. These assumptions have been based on the results of the many studies in which receptive fields were mapped with conventional stimuli, presented one at a time, against a featureless background. However, unlike the neurophysiologist's tangent screen, the natural visual scene is rich in features, and there is a growing body of evidence that in many visual neurons stimuli presented outside the CRF strongly and selectively influence neural responses to stimuli presented within the CRF. These results suggest obvious mechanisms for local-global comparisons within visuotopically organized structures. Such broad and specific surround mechanisms could participate in many functions that require the integration of inputs over wide regions of the visual space such as the perceptual constancies, the segregation of figure from ground, and depth perception through motion parallax. In the first section of this paper, we trace the historical development of the evidence of response selectivity for visual stimuli presented beyond the CRF; in the second, examine the anatomical pathways that sub serve these far-reaching surround mechanisms; and in the third, explore the possible relationships between these mechanisms and perception.
An eye to the future: exhaled nitric oxide as a predictor of clinical outcomes in asthma
Authors: D. R. Taylor
Journal: European Respiratory Journal (2010)

Recent guidelines for the management of asthma now emphasise the importance of anticipating what lies ahead. The concept of “future risk” has been introduced into our clinical terminology 1. While it may be argued that clinicians have always intuitively paid attention to ideas of future risk as well as future benefit, it is only recently that these have been articulated. Future risk refers to the risk of adverse outcomes such as exacerbations, poor asthma control, accelerated decline in lung function or side-effects of treatment in the near or distant future 2. Similarly, although anticipating future benefit may seem easy, it is not: the response to most asthma treatments is heterogeneous, and predicting those who are likely to benefit from a therapeutic intervention is possible in only a proportion of patients. This is particularly true for anti-inflammatory treatment 3, 4, and many clinicians prescribe empirically.

In asthma studies, the effect of an intervention on some future risks ( e.g. exacerbations) may be measured directly, or inferences may be drawn from measuring physiological variables or biomarkers. The latter are of increasing importance because the future benefits and risks associated with treatment intervention may be related to control of the underlying disease process, as reflected in biomarker levels. For asthma exacerbations, we can assess future risk in three ways. Firstly, we can identify epidemiological factors that characterise the “at risk” patient, e.g. male sex, ethnicity, smoking history 5. Second, there is the patient's individual history. The past is a good predictor of the future. …
Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial
Authors: N P Quillinan, D McIntosh, J Vernes, S Haq, C P Denton
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> The primary objective of the study was to explore safety and tolerability of hyperimmune caprine serum (AIMSPRO) in established diffuse cutaneous systemic sclerosis (SSc). Secondary objectives included assessment of potential efficacy and biological activity and exploration of candidate biomarkers. <h3>Methods</h3> This was a double-blind parallel group randomised placebo-controlled clinical trial. After informed consent 20 patients with established diffuse cutaneous SSc of greater than 3 years duration not receiving immunosuppressive therapy were randomised to receive either active (n=10) or placebo formulation (n=10) by subcutaneous twice weekly injection over 26 weeks. Clinical assessments were evaluated over 26 weeks. <h3>Results</h3> There were no safety concerns during this study. Frequency of adverse events was not different between active and placebo groups. Mean modified Rodnan Skin Score (mRSS) fell by 1.4±4.7 units with active treatment but increased by 2.1±6.4 units on placebo when baseline values were compared with 26 weeks and responder analysis showed clinically meaningful improvement in mRSS at 26 weeks in 5 (50%) of actively treated patients compared with 1 (10%) in the control group (p=0.062). PIIINP (µg/L) showed a comparatively larger increase in the treatment group compared with the placebo group, (p=0.0118). <h3>Conclusions</h3> These results confirm tolerability and safety of this novel biological agent in established diffuse SSc. The value of a placebo treated control group in small clinical trials evaluating skin disease in SSc is confirmed. Potential improvement in mRSS and changes in PIIINP in cases receiving active therapy suggest that this intervention may be of clinical benefit and warrants further evaluation.
Patterns of Puumala virus infection in Finland
Authors: Angie Rose, O Vapalahti, O Lyytikäinen, P Nuorti
Journal: Eurosurveillance (2003)

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.
Gonadotropins and Ovarian Cancer
Authors: Jung-Hye Choi, Alice S. T. Wong, He-Feng Huang, Peter C. K. Leung
Journal: Endocrine Reviews (2007)

Ovarian epithelial cancer (OEC) accounts for 90% of all ovarian cancers and is the leading cause of death from gynecological cancers in North America and Europe. Despite its clinical significance, the factors that regulate the development and progression of ovarian cancer are among the least understood of all major human malignancies. The two gonadotropins, FSH and LH, are key regulators of ovarian cell functions, and the potential role of gonadotropins in the pathogenesis of ovarian cancer is suggested. Ovarian carcinomas have been found to express specific receptors for gonadotropins. The presence of gonadotropins in ovarian tumor fluid suggests the importance of these factors in the transformation and progression of ovarian cancers as well as being prognostic indicators. Functionally, there is evidence showing a direct action of gonadotropins on ovarian tumor cell growth. This review summarizes the key findings and recent advances in our understanding of these peptide hormones in ovarian cancer development and progression and their role in potential future cancer therapy. We will first discuss the supporting evidence and controversies in the "gonadotropin theory" and the use of animal models for exploring the involvement of gonadotropins in the etiology of ovarian cancer. The role of gonadotropins in regulating the proliferation, survival, and metastasis of OEC is next summarized. Relevant data from ovarian surface epithelium, which is widely believed to be the precursor of OEC, are also described. Finally, we will discuss the clinical applications of gonadotropins in ovarian cancer and the recent progress in drug development.
Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I–III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial
Authors: Gustavo Ismael, Roberto Hegg, Susanne Muehlbauer, Dominik Heinzmann, Bert Lum, Sung-Bae Kim, Tadeusz Pienkowski, Mikhail Lichinitser, Vladimir Semiglazov, Bohuslav Melichar, Christian Jackisch
Journal: The Lancet Oncology (2012)
Glucose Abnormalities in Patients with Hepatitis C Virus Infection: Epidemiology and pathogenesis 
Authors: A. Lecube
Journal: Diabetes Care (2006)

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, affecting ∼3% of the world’s population (1,2). The disease is characterized by silent onset in most infected individuals (3), and recent studies indicate that the rate of progression to advanced liver disease might be lower than previously assumed (4–6). If we consider that most HCV-infected persons are <50 years of age, the burden of disease associated with HCV infection is likely to increase during the next 10–20 years as this cohort reaches the age at which complications of chronic liver disease typically occur (7).

The prevalence of type 2 diabetes in people living in the developed world ranges from 2.0 to 9.4% (8), rising to 12.3% in U.S. adults between 40 and 74 years of age (9). The decline in mortality of people with diabetes, together with the rapidly increasing frequency of obesity and the sedentary lifestyle of the population portends a dramatic increase in the prevalence rates of type 2 diabetes (10–11). Therefore, both HCV liver disease and type 2 diabetes are two already prevalent diseases that will probably continue to increase in the next decades.

HCV mainly affects the liver, but also several tissues outside the liver have been reported to be involved, resulting in a wide spectrum of extrahepatic manifestations (12–14). During the last decade, it has been hypothesized that diabetes could be one more of these extrahepatic conditions attributable to HCV infection. This raises the intriguing question of whether the rise in HCV infection is contributing to the increasing prevalence of type 2 diabetes.

In this review, the available information concerning the epidemiological association between HCV infection and diabetes is summarized. In addition, the physiopathological mechanisms related to the association between HCV and diabetes …
BIOMETRY OF CALCIUM, INORGANIC PHOSPHORUS, CHOLESTEROL, AND LECITHIN IN THE BLOOD OF RABBITS
Authors: Alvin R. Harnes
Journal: The Journal of Experimental Medicine (1929)

Experiments are reported in which it was shown that the calcium, inorganic phosphorus, cholesterol, and lecithin in the blood of normal rabbits were influenced by inoculation with a malignant tumor (4). Animals in which death was due to tumor gave results on which the following conclusions are based: 1. A marked increase in inorganic phosphorus of blood serum and cholesterol of whole blood followed inoculation. 2. The ratios of cholesterol to calcium and lecithin to calcium increased in trend, while the calcium to inorganic phosphorus, lecithin to cholesterol, and lecithin to inorganic phosphorus ratios showed a marked decrease in trend. 3. The r cholesterol-lecithin were all negative.
Analysis of cell cycle-related proteins in mediastinal lymph nodes of patients with N2-NSCLC obtained by EBUS-TBNA: relevance to chemotherapy response
Authors: S Mohamed, K Yasufuku, T Nakajima, K Hiroshima, R Kubo, A Iyoda, S Yoshida, M Suzuki, Y Sekine, K Shibuya, A Farouk, T Fujisawa
Journal: Thorax (2008)

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate tool for lymph node staging of non-small cell lung cancer (NSCLC). Most patients with NSCLC require systemic chemotherapy during their treatment, with relatively poor responses. If the response to chemotherapy could be predicted, ideally at the time of the initial bronchoscopic examination, the therapeutic benefit could be maximised while limiting toxicity. A study was therefore undertaken to investigate the feasibility of EBUS-TBNA for obtaining tissue samples from mediastinal lymph nodes that can be used for immunohistochemical analysis, and to stratify patients with molecular-based pN2-NSCLC into chemo-responsive and chemoresistant subgroups who might benefit from tailoring of chemotherapy.The expression of six cell cycle-related proteins (pRb, cyclin D1, p16(INK4A), p53, p21(Waf1), Ki-67) in mediastinal lymph node specimens obtained by EBUS-TBNA was investigated by immunohistochemistry in 36 patients with pN2-NSCLC. Their predictive role(s) in the response to platinum-based chemotherapy was examined.Immunostaining was feasible in all studied specimens. Univariate analysis revealed that p53 and p21(Waf1) expressions were significantly related to the response to chemotherapy (p = 0.002 and p = 0.011, respectively). Multivariate logistic regression analysis revealed that only p53 overexpression was associated with a poor response to chemotherapy (p = 0.021).These results suggest that EBUS-TBNA is a feasible tool for obtaining mediastinal nodal tissue samples amenable for immunohistochemical analysis. Immunostaining of p53 in EBUS-TBNA-guided specimens may be useful in predicting the response to chemotherapy in patients with N2-NSCLC and helping in the selection of patients who might benefit from certain chemotherapeutic strategies.
The Gamma Knife
Authors: L. Dade Lunsford
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Stereotaxic radiosurgery refers to a technique whereby an intracranial target can be destroyed by ionizing beams of radiation that are directed with stereotaxic precision, without the need for a surgical incision. Lars Leksell, MD, PhD, defined the field and the term in 1951.<sup>1-3</sup>Working together with physicist Borje Larrson at the Gustav Werner Institute, Uppsala, Sweden, Leksell first used orthovoltage roentgenographic techniques, then a proton beam generated by a synchrocyclotron, and eventually a linear accelerator to deliver, in a single session, a high dose of radiation to a defined volume in the brain. Because of complexity and imprecision, Leksell subsequently abandoned work with these devices and instead he and Larrson arranged for construction of the first true stereotaxic radiosurgical unit, the gamma knife. In 1968, the first gamma knife was used under the direction of Leksell at an affiliated hospital of the Karolinska Institute in Stockholm.
Will SUMMIT reach the peak in COPD?
Authors: Samy Suissa
Journal: Thorax (2014)

The Study to Understand Mortality and Morbidity in COPD (SUMMIT) is a randomised controlled trial conducted in patients with COPD and comorbid cardiovascular disease, designed to assess the ‘impact of Fluticasone Furoate/Vilanterol combination (FF/VI) and its individual components on the survival of patients with moderate COPD and either a history of CVD or at increased risk for CVD’.1 Fluticasone furoate is an inhaled corticosteroid (ICS) and vilanterol is a long-acting β-agonist (LABA). The trial is enrolling 16 000 such patients with moderate COPD randomly assigned to once daily treatment with this ICS–LABA combination, the ICS only, the LABA only or placebo. Patients in this event-driven trial will be followed up until 1000 deaths occur, which is expected to take up to 44 months. Mortality is the primary endpoint and the primary comparison is between the ICS–LABA combination and placebo. The study is designed as a superiority trial with 90% power to detect a 30% reduction in all-cause mortality when comparing the ICS–LABA with placebo at the two-sided 1% significance level. Secondary endpoints will also be studied, including lung function decline and composite cardiovascular events.

The design of SUMMIT is similar to that of the Towards a Revolution in COPD Health (TORCH) trial,2 with the exception that SUMMIT focuses on a study population of patients with moderate COPD and at cardiovascular risk. As well, while all patients in TORCH were followed for an exact 3-year period, SUMMIT being event-driven is expected to follow-up patients between 15 and 44 months.

At first glance, the SUMMIT trial appears to have set unattainable goals. Indeed, the magnitude of the targeted effect in terms of power, a 30% reduction in all-cause mortality (HR=0.70), seems overly ambitious. In the TORCH trial, the target for this same outcome was a 27% reduction (HR=0.73) with an even smaller sample …
Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation
Authors: Angela Dispenzieri, Martha Q. Lacy, Jerry A. Katzmann, S. Vincent Rajkumar, Roshini S. Abraham, Suzanne R. Hayman, Shaji K. Kumar, Raynell Clark, Robert A. Kyle, Mark R. Litzow, David J. Inwards, Stephen M. Ansell, Ivana M. Micallef, Luis F. Porrata, Michelle A. Elliott, Patrick B. Johnston, Philip R. Greipp, Thomas E. Witzig, Steven R. Zeldenrust, Stephen J. Russell, Dennis Gastineau, Morie A. Gertz
Journal: Blood (2006)
Patch Testing for Methylisothiazolinone and Methylchloroisothiazolinone-Methylisothiazolinone Contact Allergy
Authors: Sherry H. Yu, Apra Sood, James S. Taylor
Journal: JAMA Dermatology (2015)

Contact allergy to methylisothiazolinone (MI) or to the combined formulation of methylchloroisothiazolinone and MI (MCI-MI) has increased significantly, with a frequency of as much as 11.1% in patients with dermatitis; however, few cohort studies in the US population have been reported.To investigate the prevalence of contact allergies to MI and MCI-MI and the outcomes of patients with positive patch test reactions to MI and MCI-MI.Retrospective medical record review of all consecutive patients (n = 703) presenting with possible allergic contact dermatitis and subsequently undergoing patch testing at a tertiary referral center from January 1, 2012, through November 30, 2014. Patch testing used the North American Contact Dermatitis Group standard series. The MCI-MI concentration was 100 ppm; the MI concentration in the screening series increased from 200 to 2000 ppm in January 2013. Demographic data, exposures, and outcomes were reported for patients with positive patch test reactions to MI and/or MCI-MI. Data were analyzed from December 1, 2014, through January 31, 2015.Positive patch test reaction to MI and/or MCI-MI and identification of the relevance of contact allergy to these preservatives. Follow-up after allergen avoidance was determined when available.Of the 703 patients who underwent patch testing, contact allergy to MI and/or MCI-MI occurred in 57 patients (8.1%), with 35 reactions to MI only, 5 reactions to MCI-MI only, and 17 reactions to both. Prevalence of contact allergy to MI increased from 6 of 236 patients (2.5%) in 2012 to 16 of 235 patients (6.8%) in 2014. The most commonly affected sites were the hands and face. Contact allergy to MI and/or MCI-MI was occupationally related in 4 cases. Cosmetics, soaps and cleansers (including wet wipes), and hair care products accounted for all identified sources. Twenty-three patients had follow-up data, and 17 of these (74%) improved with allergen avoidance.The increasing prevalence of contact allergy to MI alone supports its addition to the standard series to identify cases missed by testing only for MCI-MI. Recent regulations by the European Commission have banned MCI-MI in all leave-on body products as of July 16, 2015. Currently recommended US regulations are less stringent; however, US regulatory agencies must act to ensure patient safety.
Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.
Authors: M P Cooke, A W Heath, K M Shokat, Y Zeng, F D Finkelman, P S Linsley, M Howard, C C Goodnow
Journal: The Journal of Experimental Medicine (1994)

The specificity of antibody (Ab) responses depends on focusing helper T (Th) lymphocyte signals to suitable B lymphocytes capable of binding foreign antigens (Ags), and away from nonspecific or self-reactive B cells. To investigate the molecular mechanisms that prevent the activation of self-reactive B lymphocytes, the activation requirements of B cells specific for the Ag hen egg lysozyme (HEL) obtained from immunoglobulin (Ig)-transgenic mice were compared with those of functionally tolerant B cells isolated from Ig-transgenic mice which also express soluble HEL. To eliminate the need for surface (s)Ig-mediated Ag uptake and presentation and allow the effects of sIg signaling to be studied in isolation, we assessed the ability of allogeneic T cells from bm12 strain mice to provide in vivo help to C57BL/6 strain-transgenic B cells. Interestingly, non-tolerant Ig-transgenic B cells required both allogeneic Th cells and binding of soluble HEL for efficient activation and Ab production. By contrast, tolerant self-reactive B cells from Ig/HEL double transgenic mice responded poorly to the same combination of allogeneic T cells and soluble HEL. The tolerant B cells were nevertheless normally responsive to stimulation with interleukin 4 and anti-CD40 Abs in vitro, suggesting that they retained the capacity to respond to mediators of T cell help. However, the tolerant B cells exhibited a proximal block in the sIg signaling pathway which prevented activation of receptor-associated tyrosine kinases in response to the binding of soluble HEL. The functional significance of this sIg signaling defect was confirmed by using a more potent membrane-bound form of HEL capable of triggering sIg signaling in tolerant B cells, which markedly restored their ability to collaborate with allogeneic Th cells and produce Ab. These findings indicate that Ag-specific B cells require two signals for mounting a T cell-dependent Ab response and identify regulation of sIg signaling as a mechanism for controlling self-reactive B cells.
Experimental induction of rheumatoid factor and joint lesions in rabbits after intravenous injections of killed bacteria.
Authors: A C Hanglow, C J Welsh, P Conn, J M Pitts, A Rampling, R R Coombs
Journal: Annals of the Rheumatic Diseases (1986)

Rabbits receiving repeated intravenous injections of killed bacteria (Escherichia coli or Bacillus subtilis) developed IgM rheumatoid factor which reacted with autologous heat-aggregated IgG. In addition, 5/7 9Old English9 and 7/8 9Sandy Lop9 rabbits receiving killed E. coli developed rheumatoid-like synovial lesions. 9Old English9 rabbits developed lesions of a more severe nature. Three of eight 9Sandy Lop9 rabbits injected with killed B. subtilis had high levels of rheumatoid factor but only mild joint lesions.