tbuckley/cabot-search huggingface dataset:
Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria
Authors: Helen E. Jenkins, R. Bruce Aylward, Alex Gasasira, Christl A. Donnelly, Michael Mwanza, Jukka Corander, Sandra Garnier, Claire Chauvin, Emmanuel Abanida, Muhammad Ali Pate, Festus Adu, Marycelin Baba, Nicholas C. Grassly
Journal: New England Journal of Medicine (2010)

The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV).We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared.No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV.The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge.
Setting the Bar in Phase II Trials: The Use of Historical Data for Determining “Go/No Go” Decision for Definitive Phase III Testing
Authors: Andrew J. Vickers, Vennus Ballen, Howard I. Scher
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Phase II trials aim to determine whether a cancer treatment is sufficiently promising to justify phase III study. Whether an agent is declared promising in a phase II trial depends on prespecified “null” and “alternative” rates of an outcome of interest such as tumor response. In some cases, the null must be determined with reference to historical data. We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived. Experimental Design: We conducted a systematic review of phase II trials published in the Journal of Clinical Oncology or Cancer in the 3 years to June 2005. Data were extracted following a prespecified protocol. Results: We retrieved 251 papers, of which 117 were found to be ineligible; 70 of 134 included trials (52%) were defined as requiring historical data for design. Nearly half (32, 46%) of these papers did not cite the source of the historical data used, and just 9 (13%) clearly gave a single historical estimate as the rationale for the null. Trials that failed to cite prior data appropriately were significantly more likely to declare an agent to be active (82% versus 33%; P = 0.005). No study incorporated statistical methods to account for either sampling error or possible differences in case mix between the phase II sample and the historical cohort. Conclusions: Many phase II trials require historical data to determine null response rates. Simple guidelines may improve design and reporting of such trials.
Use of transcutaneous oxygen tension, arterial oxygen saturation, and respiratory resistance to assess the response to inhaled methacholine in asthmatic children and normal adults.
Authors: N M Wilson, S B Phagoo, M Silverman
Journal: Thorax (1991)

Respiratory resistance (Rrs6), transcutaneous oxygen tension (PtcO2), and oxygen saturation (SaO2) were measured during methacholine challenge in 15 asthmatic children and six normal adults. During bronchoconstriction, induced by a wide range of inhaled methacholine concentrations (0.5-256 g/l), the rise in Rrs6 was reflected by a fall in PtcO2 in all subjects. Although there was a significant mean fall in SaO2 at maximum bronchoconstriction there was no consistent relation between changes in SaO2 and Rrs6. The inhaled dose of methacholine causing a 40% increase in Rrs6 (PD40Rrs6) and a 20% fall in PtCO2 (PD20PtcO2) was calculated for each subject. There was no significant difference in mean PD40Rrs6 and PD20PtcO2, and the relation between the two was similar in the asthmatic children and the normal adults. It was therefore concluded that the measurement of PtcO2, but not SaO2, during methacholine challenge can be used for the assessment of bronchial responsiveness, and that it could prove particularly useful for children too young to cooperate with lung function tests.
Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease
Authors: Marie-Pierre Audrézet, Christine Corbiere, Said Lebbah, Vincent Morinière, Françoise Broux, Ferielle Louillet, Michel Fischbach, Ariane Zaloszyc, Sylvie Cloarec, Elodie Merieau, Véronique Baudouin, Georges Deschênes, Gwenaelle Roussey, Sandrine Maestri, Chiara Visconti, Olivia Boyer, Carine Abel, Annie Lahoche, Hanitra Randrianaivo, Lucie Bessenay, Djalila Mekahli, Ines Ouertani, Stéphane Decramer, Amélie Ryckenwaert, Emilie Cornec-Le Gall, Rémi Salomon, Claude Ferec, Laurence Heidet
Journal: Journal of the American Society of Nephrology (2015)

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.
Anterior Chamber Depth Is Significantly Decreased after Scleral Buckling Surgery
Authors: Fleur Goezinne, Ellen C. La Heij, Tos T.J.M. Berendschot, Nayyirih G. Tahzib, Diana W.K.J. Cals, Albert T.A. Liem, Igor J. Lundqvist, Fred Hendrikse
Journal: Ophthalmology (2009)
Selective parasympathetic innervation of subcutaneous and intra-abdominal fat — functional implications
Authors: Felix Kreier, Eric Fliers, Peter J. Voshol, Corbert G. Van Eden, Louis M. Havekes, Andries Kalsbeek, Caroline L. Van Heijningen, Arja A. Sluiter, Thomas C. Mettenleiter, Johannes A. Romijn, Hans P. Sauerwein, Ruud M. Buijs
Journal: Journal of Clinical Investigation (2002)

The wealth of clinical epidemiological data on the association between intra-abdominal fat accumulation and morbidity sharply contrasts with the paucity of knowledge about the determinants of fat distribution, which cannot be explained merely in terms of humoral factors. If it comes to neuronal control, until now, adipose tissue was reported to be innervated by the sympathetic nervous system only, known for its catabolic effect. We hypothesized the presence of a parasympathetic input stimulating anabolic processes in adipose tissue. Intra-abdominal fat pads in rats were first sympathetically denervated and then injected with the retrograde transneuronal tracer pseudorabies virus (PRV). The resulting labeling of PRV in the vagal motor nuclei of the brain stem reveals that adipose tissue receives vagal input. Next, we assessed the physiological impact of these findings by combining a fat pad-specific vagotomy with a hyperinsulinemic euglycemic clamp and RT-PCR analysis. Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51%. Moreover, expression of resistin and leptin mRNA decreased, whereas adiponectin mRNA did not change. All these data indicate an anabolic role for the vagal input to adipose tissue. Finally, we demonstrate somatotopy within the central part of the autonomic nervous system, as intra-abdominal and subcutaneous fat pads appeared to be innervated by separate sympathetic and parasympathetic motor neurons. In conclusion, parasympathetic input to adipose tissue clearly modulates its insulin sensitivity and glucose and FFA metabolism in an anabolic way. The implications of these findings for the (patho)physiology of fat distribution are discussed.
THE STANDARDIZATION OF ANTIPNEUMOCOCCIC SERUM TYPES I AND II
Authors: José Zozaya, John Boyer, Janet Clark
Journal: The Journal of Experimental Medicine (1930)

1. The mouse protection test used for the standardization of anti-pneumococcic serum Type I and II is very unreliable. 2. The specific polysaccharide precipitation test can be used to establish the comparative value of a test serum to a standardized serum. 3. The polysaccharide used for such tests does not have to be of the highest purity.
NHS patient safety incidents rise by 12% in six months, as reporting culture grows
Authors: A. O'Dowd
Journal: BMJ (2009)

Reported incidents that compromised patient safety in the NHS in England rose by 12% in a six month period, with an even steeper rise in primary care organisations.

Figures from the National Patient Safety Agency released on 7 October show that 459 500 incidents were reported to have happened between 1 October 2008 and 31 March 2009.

This is a 12% increase on the previous six months, but primary care organisations had a 25% rise in incidents, such as errors, complications, or inadvertent injuries.

The rises were largely the result of more reporting and an …
Chronic Traumatic Encephalopathy: Historical Origins and Current Perspective
Authors: Philip H. Montenigro, Daniel T. Corp, Thor D. Stein, Robert C. Cantu, Robert A. Stern
Journal: Annual Review of Clinical Psychology (2015)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.
Smoking cessation strategies in patients with COPD
Authors: Miriam J. Warnier, Evelien E.S. van Riet, Frans H. Rutten, Marie Louise De Bruin, Alfred P.E. Sachs
Journal: European Respiratory Journal (2012)

Smoking cessation is the cornerstone of treatment of chronic obstructive pulmonary disease (COPD) patients. This systematic review evaluates the effectiveness of behavioural and pharmacological smoking cessation strategies in COPD patients. MEDLINE was searched from January 2002 to October 2011. Randomised controlled trials evaluating the effect of smoking cessation interventions for COPD patients, published in English, were selected. The methodological quality of included trials was assessed using the Delphi list by two reviewers independently. The relative risks of smoking cessation due to the intervention, compared with controls, were calculated. Eight studies met the inclusion criteria. Heterogeneity was observed for study population, the intervention strategy, the follow-up period and the outcome. According to the Delphi list methodological quality scores, five studies were considered to be of acceptable quality. Pharmacological therapy combined with behavioural counselling was more effective than each strategy separately. In COPD patients, the intensity of counselling did not seem to influence the results, nor did the choice of drug therapy make a difference. This systematic review makes clear that in COPD patients, pharmacological therapy combined with behavioural counselling is more effective than each strategy separately. Neither the intensity of counselling nor the type of anti-smoking drug made a difference.
Vascular Endothelial Growth Factor Activation of Sterol Regulatory Element Binding Protein
Authors: Rui-Hai Zhou, Min Yao, Tzong-Shyuan Lee, Yi Zhu, Manuela Martins-Green, John Y.-J. Shyy
Journal: Circulation Research (2004)

By stimulating the migration and proliferation of endothelial cells (ECs), vascular endothelial growth factor (VEGF) is a potent angiogenic factor. However, the molecular mechanism involved in the VEGF-induced angiogenesis remains elusive. We hypothesized that sterol regulatory element binding proteins (SREBPs), transcription factors governing cellular lipid homeostasis, play an important role in regulating angiogenesis in response to VEGF. VEGF activated SREBP1 and SREBP2 in ECs, as demonstrated by the increased SREBPs, their cleavage products, and the upregulation of the targeted genes. VEGF-induced SREBP activation depended on SREBP cleavage-activating protein (SCAP), because knocking down SCAP by RNA interference (RNAi) inhibited SREBP activation in response to VEGF. SREBP activation was also blocked by 25-hydroxycholesterol (25-HC). To verify the functional implication of SREBPs in VEGF-induced angiogenesis, we tested the role of SREBPs in EC migration and proliferation. SCAP RNAi or 25-HC inhibited VEGF-induced pseudopodia extension and migration of ECs. Both treatments inhibited VEGF-induced EC proliferation, with cell growth arrested at the G(0)/G(1) phase and a concomitant decrease of the S phase. Blocking the PI3K-Akt pathway inhibited the VEGF-activated SREBPs, demonstrating that PI3K-Akt regulates SREBPs. Consistent with our in vitro data, SREBP1 was detected in newly developed microvasculatures in a rabbit skin partial-thickness wound-healing model. SREBP inhibition also markedly suppressed VEGF-induced angiogenesis in chick embryos. In summary, this study identifies SREBPs as the key molecules in regulating angiogenesis in response to VEGF.
The natural soluble form of IL-18 receptor β exacerbates collagen-induced arthritis via modulation of T-cell immune responses
Authors: S Veenbergen, R L Smeets, M B Bennink, O J Arntz, L A B Joosten, W B van den Berg, F A J van de Loo
Journal: Annals of the Rheumatic Diseases (2009)

Objective: IL-18 is a pluripotent cytokine that has been implicated in the development of rheumatoid arthritis. A soluble form of the IL-18 receptor accessory protein (sIL-18Rβ) with unknown function has recently been identified. This study examined the ability of sIL-18Rβ to inhibit IL-18 biological activities and to modulate immune responses during collagen-induced arthritis (CIA). Methods: Adenoviruses encoding sIL-18Rβ were administered intravenously in type II collagen-immunised DBA/1 mice. Humoral responses were analysed by determining anti-bovine collagen type II (BCII) antibody levels by ELISA. Cytokine production by splenic T cells and cytokine levels in serum were measured by Luminex multi-analyte technology. CD4 + CD25 + Foxp3 + regulatory T cells (Treg) were measured by flow cytometry. Results: Intravenous delivery of Ad5.sIL-18Rβ in collagen-immunised mice led to enhanced transgene expression in splenic antigen-presenting cells (APC). A co-culture of these sIL-18Rβ-transduced APC with purified splenic CD3 + T cells led to a marked inhibition of IL-18-induced IFNγ, IL-4 and IL-17 production by CD3 + T cells. Remarkably, systemic treatment with Ad5.sIL-18Rβ caused an exacerbation of arthritis, and histological evaluation of knee joints showed increased cartilage and bone erosion. No significant differences were observed in anti-BCII antibodies, but the aggravation was accompanied by decreased IFNγ (−30%) and IL-4 (−44%) and increased IL-17 (+84%) production by splenic CD3 + T cells. In addition, reduced circulating levels of CD4 + CD25 + Foxp3 + Treg and anti-inflammatory IL-10 were shown. Conclusion: This study identifies sIL-18Rβ as a novel IL-18 inhibitor, which promotes CIA after intravenous overexpression by affecting Treg levels and supporting a T helper type 17 response.
Prevalence of Recurrent Wheezing in Infancy: Time Trends in the EISL Phase III
Authors: H.J. Chong Neto, N.A. Rosário, F.C. Silva, L.F.M. Bojarski, E.A. Grasselli, C.S. Rosário, B.A. Rosário, F.H. Chong
Journal: Journal of Allergy and Clinical Immunology (2011)
HER-2 Signaling, Acquisition of Growth Factor Independence, and Regulation of Biological Networks Associated with Cell Transformation
Authors: Aliccia Bollig-Fischer, Michele Dziubinski, Alaina Boyer, Ramsi Haddad, Craig N. Giroux, Stephen P. Ethier
Journal: Cancer Research (2010)

Abstract Activated oncogenes are the dominant drivers of malignant progression in human cancer, yet little is known about how the transformation from proto-oncogene to activated oncogene drives the expression of transformed phenotypes. An isogenic model of HER-2–mediated transformation of human mammary epithelial cells was used along with HER-2–amplified human breast cancers to investigate how HER-2 activation alters its properties as a signaling molecule and changes the networks of HER-2–regulated genes. Our results show that full oncogenic activation of HER-2 is the result of a transition in which activated HER-2 acquires dominant signaling properties that qualitatively alter the network of genes regulated by the activated oncogene compared with the proto-oncogene. Consequently, gene expression programs related to invasion, cell stress, and stemness become regulated by HER-2 in a manner not observed in nontransformed cells, even when HER-2 is overexpressed. Our results offer novel insights into biological processes that come under the control of HER-2 after it acquires full oncogenic potential. Cancer Res; 70(20); 7862–73. ©2010 AACR.
VENEREAL SPIROCHETOSIS IN AMERICAN RABBITS
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1922)

Of 50 rabbits, otherwise regarded as normal, three adult females and two adult males (10 per cent) have been found to have in their genitoperineal region certain papulosquamous, often ulcerating, lesions. A recently purchased group of twenty rabbits contained six females (30 per cent) with similar lesions. This condition runs a chronic course and is characterized by the presence of a spiral organism closely resembling Treponema pallidum. The rabbit spirochete has the same morphological features as Treponema pallidum; it is possibly a trifle thicker and longer than the average pallidum. Long specimens measuring 30 µ are frequently encountered, and they show a tendency to form loosely entangled knots. A stellate arrangement of several organisms in a mass is frequently observed. In the lesion of one rabbit there were two types of spirochete, one of the variety just described, the other a somewhat coarser organism, closely resembling Treponema calligyrum found in a human condyloma, but a trifle thinner and longer. This organism is perhaps merely a variant type of the rabbit spirochete. The histological reactions are similar to, but considerably less cellular, than those occurring in typical primary syphilitic lesions. There is a marked hyperkeratosis and interpapillary infiltration not observed in scrotal chancre. The disease is transmissible to normal rabbits, in which the usual papular lesions can be readily reproduced in the genitoperineal region. In the first passages the incubation period varied from 20 to 88 days; subsequently one of the strains produced a lesion in 20 days on the second, and in 5 days on the third passage. No typical orchitis or keratitis was produced in the rabbits of the present series, although in one of the original rabbits (No. 4) scaly, papular lesions have developed on the nose, lips, eyelid, and paws. Monkeys (Macacus rhesus) failed to show any lesions within a period of 4 months after inoculation. In one instance transmission was accomplished through the mating of an infected female with a normal male. The Wassermann reaction was uniformly negative in the five rabbits with spontaneous lesions and in eighteen rabbits experimentally infected. Salvarsan had the same therapeutic effect on the lesions produced by the rabbit spirochete as on the experimental pallidum lesion of the rabbit. The organism belongs to the genus Treponema, and may be designated Treponema cuniculi.
Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions
Authors: Toshimasa Yamauchi, Yasunori Nio, Toshiyuki Maki, Masaki Kobayashi, Takeshi Takazawa, Masato Iwabu, Miki Okada-Iwabu, Sachiko Kawamoto, Naoto Kubota, Tetsuya Kubota, Yusuke Ito, Junji Kamon, Atsushi Tsuchida, Katsuyoshi Kumagai, Hideki Kozono, Yusuke Hada, Hitomi Ogata, Kumpei Tokuyama, Masaki Tsunoda, Tomohiro Ide, Kouji Murakami, Motoharu Awazawa, Iseki Takamoto, Philippe Froguel, Kazuo Hara, Kazuyuki Tobe, Ryozo Nagai, Kohjiro Ueki, Takashi Kadowaki
Journal: Nature Medicine (2007)