tbuckley/cabot-search huggingface dataset:
Bifidobacteria and subsets of dendritic cells: friendly players in immune regulation!: Figure 1
Authors: Corinne Grangette
Journal: Gut (2011)

The mammalian gastrointestinal tract harbours a vast number of bacterial residents, recently referred to as the microbiota, which are instrumental in supporting energy metabolism and immune function of the host. A large number of studies have highlighted the fact that certain (pathogenic) micro-organisms can be harmful to the health of their host, while more recently an increasing number of papers have attributed direct beneficial health effects to the gut microbial community. As these bacteria encode 100 times more genes than present in the human genome, the partnership of the host with its microbiota constitute a ‘superorganism’.1 Homoeostasis in this superorganism is sustained through an optimal cohabitation of the host with this microbiota, keeping the balance between commensals and pathogens, but also between proinflammatory and regulatory responses. The composition of the gut microbiota has indeed been shown to be an important determinant of Th17:Treg balance and may thus influence intestinal immunity and tolerance.2 Disturbing alterations in the composition of the microbiota (a process known as dysbiosis) will compromise such homoeostasis and promote the development of various inflammatory disorders, such as inflammatory bowel disease. An in-depth understanding of the mechanisms underlying host–symbiont relationships will be pivotal for the development of new therapeutic or prophylactic interventions targeting the intestinal microbiota.

One such approach is the use of probiotics, mainly lactobacilli and bifidobacteria, to impact on …
New policies to address the global burden of childhood cancers
Authors: Richard Sullivan, Jerzy R Kowalczyk, Bharat Agarwal, Ruth Ladenstein, Edel Fitzgerald, Ronald Barr, Eva Steliarova-Foucher, Ian Magrath, Scott C Howard, Mariana Kruger, Maria Grazia Valsecchi, Andrea Biondi, Paul Grundy, Malcolm A Smith, Peter Adamson, Gilles Vassal, Kathy Pritchard-Jones
Journal: The Lancet Oncology (2013)
Ultraviolet light induction of peripheral granulocytosis with splenomegaly: protection of mice with topical p-aminobenzoic acid (PABA)
Authors: H. FLINDT-HANSEN, P. EBBESEN
Journal: British Journal of Dermatology (1991)

Journal Article Ultraviolet light induction of peripheral granulocytosis with splenomegaly: protection of mice with topical p‐aminobenzoic acid (PABA) Get access H. FLINDT‐HANSEN, H. FLINDT‐HANSEN Department of Dermatolosn, Ullevaal University Hospital, Oslo, Norwan Dr Henrik Plindt‐Hansen, Department of Dermatology, Ullevaal Hospital, Oslo 4, Norway. Search for other works by this author on: Oxford Academic Google Scholar P. EBBESEN P. EBBESEN Department of Virus and Cancer, The Danish Cancer Society, Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 3, 1 September 1991, Pages 222–226, https://doi.org/10.1111/j.1365-2133.1991.tb14744.x Published: 01 September 1991
The Prospective Course of Rapid-Cycling Bipolar Disorder: Findings From the STEP-BD
Authors: Christopher D. Schneck, David J. Miklowitz, Sachiko Miyahara, Mako Araga, Stephen Wisniewski, Laszlo Gyulai, Michael H. Allen, Michael E. Thase, Gary S. Sachs
Journal: American Journal of Psychiatry (2008)

In a naturalistic follow-up of adult bipolar patients, the authors examined the contributions of demographic, phenomenological, and clinical variables, including antidepressant use, to prospectively observed mood episode frequency.For 1,742 bipolar I and II patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), episodes of mood disorders were evaluated for up to 1 year of treatment.At entry, 32% of the patients met the DSM-IV criteria for rapid cycling in the prestudy year. Of the 1,742 patients, 551 (32%) did not complete 1 year of treatment. Among the 1,191 patients remaining, those with prior rapid cycling (N=356) were more likely to have further recurrences, although not necessarily more than four episodes per year. At the end of 12 months, only 5% (N=58) of the patients could be classified as rapid cyclers; 34% (N=409) had no further mood episodes, 34% (N=402) experienced one episode, and 27% (N=322) had two or three episodes. Patients who entered the study with earlier illness onset and greater severity were more likely to have one or more episodes in the prospective study year. Antidepressant use during follow-up was associated with more frequent mood episodes.While DSM-IV rapid cycling was prospectively observed in only a small percentage of patients, the majority of these patients had continued recurrences at lower but clinically significant rates. This suggests that cycling is on a continuum and that prevention of recurrences may require early intervention and restricted use of antidepressants.
Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data
Authors: Brian S Hooker
Journal: Translational Neurodegeneration (2014)

A significant number of children diagnosed with autism spectrum disorder suffer a loss of previously-acquired skills, suggesting neurodegeneration or a type of progressive encephalopathy with an etiological basis occurring after birth. The purpose of this study is to investigate the effectof the age at which children got their first Measles-Mumps-Rubella (MMR) vaccine on autism incidence. This is a reanalysis of the data set, obtained from the U.S. Centers for Disease Control and Protection (CDC), used for the Destefano et al. 2004 publication on the timing of the first MMR vaccine and autism diagnoses.The author embarked on the present study to evaluate whether a relationship exists between child age when the first MMR vaccine was administered among cases diagnosed with autism and controls born between 1986 through 1993 among school children in metropolitan Atlanta. The Pearson's chi-squared method was used to assess relative risks of receiving an autism diagnosis within the total cohort as well as among different race and gender categories.When comparing cases and controls receiving their first MMR vaccine before and after 36 months of age, there was a statistically significant increase in autism cases specifically among African American males who received the first MMR prior to 36 months of age. Relative risks for males in general and African American males were 1.69 (p=0.0138) and 3.36 (p=0.0019), respectively. Additionally, African American males showed an odds ratio of 1.73 (p=0.0200) for autism cases in children receiving their first MMR vaccine prior to 24 months of age versus 24 months of age and thereafter.The present study provides new epidemiologic evidence showing that African American males receiving the MMR vaccine prior to 24 months of age or 36 months of age are more likely to receive an autism diagnosis.
The interface: crucial for successful noninvasive ventilation
Authors: M.W. Elliott
Journal: European Respiratory Journal (2003)

Noninvasive ventilation (NIV) is a real advance in the management of both chronic and acute respiratory failure. It is the absence of an endotracheal or tracheostomy tube which defines NIV. The development of various interfaces have made the delivery of effective ventilation to patients without intubation possible and a good interface is crucial to success. These can be factory manufactured or customised. Driven largely by the explosion in the diagnosis and treatment of obstructive sleep apnoea there are now a wide variety of different factory-made masks of different designs, shapes, sizes and materials. It is usually possible to find something that suits most individuals and there is seldom a need for an individually made interface. Broadly speaking there are four different types: full face masks (enclose mouth and nose), nasal masks, nasal pillows or plugs (insert directly into the nostrils), and mouthpieces. A review of published studies showed that in acute NIV facial masks predominate (63%), followed by nasal masks (31%) and nasal pillows (6%). In contrast for chronic NIV nasal masks (73%) are the most commonly used followed by nasal pillows (11%), facial masks (6%) and mouthpieces (5%) 1. More recently the use of a “helmet” has been described in hypoxaemic acute respiratory failure (ARF) with patients receiving continuous ventilation for many days 2. Nasal masks have less static dead space, are not as claustrophobic and allow expectoration and communication more easily than full face masks. The improvement in arterial blood gas tensions appears to be slower in some studies using nasal masks compared to face masks 3. A full face mask is usually chosen when there is significant mouth breathing, which is very common in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD), and at least during the initial phase results in …
Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development
Authors: Alexander Astrakhan, Miyuki Omori, Thuc Nguyen, Shirly Becker-Herman, Masanori Iseki, Theingi Aye, Kelly Hudkins, James Dooley, Andrew Farr, Charles E Alpers, Steven F Ziegler, David J Rawlings
Journal: Nature Immunology (2007)
Multiple cancers. Tumor burden permits the outgrowth of other cancers.
Authors: C A Mullen, J L Urban, C Van Waes, D A Rowley, H Schreiber
Journal: The Journal of Experimental Medicine (1985)

We demonstrate that tumor-bearing hosts permit the outgrowth of "potentially malignant" cells that are located at a different site. These second cancers continued to grow and kill their hosts even though they retain the "premalignant" phenotype, even after removal of the original malignancy. The potentially malignant cells used in these experiments were ultraviolet light- or methylcholanthrene-induced regressor tumor cells that are rejected regularly by normal mice at any testable dose, and only form progressive tumors in immunosuppressed individuals. The immunological rejection of these highly immunogenic, potentially malignant cells was suppressed by Thy-1+, Ly-2-, nonadherent, radio-sensitive suppressor cells in the tumor-bearing mice. These suppressor cells were absent in nude tumor-bearing mice. Unlike helper and cytolytic T cell-mediated responses, which are exquisitely tumor specific, the suppression caused by a progressively growing tumor was crossreactive among many syngeneic, independently derived tumors induced by different carcinogens. However, T cell-mediated immune responses to alloantigens, allogeneic tumors, certain syngeneic tumors, and humoral responses to xenogeneic red blood cells were normal in these mice. The immune suppression in the tumor-bearing animals closely simulated that induced by ultraviolet light irradiation, and both types of suppression might therefore share common mechanisms. Our findings may contribute to understanding the growth, development, and possible control of multicentric malignancies and add a precaution to the potential use of strongly immunogenic tumor variants for active immunotherapy in hosts bearing less immunogenic tumors.
Steroids do not improve RSV-related wheeze in children
Authors: R P H Tofts
Journal: Thorax (2009)

Respiratory syncytial virus (RSV)-related lower respiratory tract infection is common in infants and is often followed by recurrent wheeze and morbidity. This double-blind placebo controlled trial investigated whether early glucocorticoids prevent recurrent wheeze.

The 243 participants were infants (aged <13 months) admitted to hospital with RSV (confirmed by immunofluorescence) from …
Hemodynamic changes in patients developing effective hypovolemia after total paracentesis
Authors: Maria Carme Vila, Ricard Solà, Lluis Molina, Montserrat Andreu, Susanna Coll, Jordi Gana, Judith Marquez, Joaquin Palá, Felipe Bory, Silvia Pons, Luis Szescielinski, Wladimiro Jimenez
Journal: Journal of Hepatology (1998)
Elevated Levels of Circulating Platelet Aggregates and Beta-Thromboglobulin in Scleroderma
Authors: M. BASHAR KAHALEH
Journal: Annals of Internal Medicine (1982)

Levels of circulating platelet aggregates and plasma β-thromboglobulin reflect the degree of platelet activation in vascular injury and repair. Both values were evaluated in 38 patients with scleroderma and 18 control subjects matched for age, sex, and race. Circulating platelet aggregates (expressed as percentage of total platelet count) were 7.2 ± 5.5% (mean ± SD) in the control group and 31.2 ± 13% in the scleroderma group (p < 0.0005). Beta-thromboglobulin levels in the control group were 20 ± 10 ng/mL and 72.7 ± 50 ng/mL in the group with scleroderma (p < 0.0005). A positive correlation was found between the two values (r = 0.6, p < 0.0005). Significant reductions in circulating platelet aggregates and β-thromboglobulin levels were achieved in 10 patients by dipyridamole and aspirin therapy. These results show in-vivo activation of platelets in scleroderma with release of platelet granule constituents. Antiplatelet therapy in adequate doses returned both values to normal; however, its long-term effect on scleroderma is not yet known.
Highlights of the North American Cystic Fibrosis Conference 2011
Authors: Rishi Pabary, Rebecca Thursfield, Jane C Davies
Journal: Journal of the Royal Society of Medicine (2012)

This year's meeting was held in Anaheim, California, and was an excellent mix of basic science, translational research and clinical practice. For the first time, authors were invited to submit accepted abstracts as electronic posters (http://nacfcdl.cff.org/Pages/E-Posters.aspx). The meeting was heavily dominated by the hot-off-the-press news of the phase 3 trial results of Ivacaftor (VX-770), which is discussed in detail below. Accompanying this was a resurgence of enthusiasm surrounding the potential of CFTR as a therapeutic target, with possible implications for other small molecule approaches and gene therapy.

We have structured this review around the following areas: (a) Genetics, including newborn screening; (b) pathophysiology and animal models; (c) conventional management and monitoring and (d) progress in novel therapies.
Intensified Neoadjuvant Chemotherapy in Early-Responding Breast Cancer: Phase III Randomized GeparTrio Study
Authors: G. von Minckwitz, S. Kummel, P. Vogel, C. Hanusch, H. Eidtmann, J. Hilfrich, B. Gerber, J. Huober, S. D. Costa, C. Jackisch, S. Loibl, K. Mehta
Journal: JNCI Journal of the National Cancer Institute (2008)

Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery. The relationship between extended chemotherapy and pathological complete response at surgery was investigated in a clinical trial. Untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m 2 , doxorubicin at 50 mg/m 2 , and cyclophosphamide at 500 mg/m 2 (TAC). Those whose tumor size decreased by 50% or more by sonographic measurement (ie, reduction in the product of the two largest perpendicular diameters by at least 50%) were classified as responders and randomly assigned to receive four or six more cycles of TAC, for a total of six or eight TAC cycles. The primary aim was to increase the rate of a pathological complete response (defined as no invasive or in situ residual tumor masses in the breast and lymph nodes) from 20% to 26%. Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed. All statistical tests were two-sided. Of the 2090 patients in the GeparTrio trial, 1390 (66.5%) were randomly assigned as responders after two initial TAC cycles to receive an additional four (n = 704) or six (n = 686) TAC cycles. Rates of pathological complete response were not statistically significantly different between the arms (21.0% with six TAC cycles and 23.5% with eight TAC cycles; difference = 2.5%, 95% confidence interval [CI] = −1.8% to 6.8%; P = .27). More clinical (48.2% vs 52.9%, difference = 4.7%; 95% CI = −0.55% to 9.95%; P = .08) and sonographic (22.6% vs 27.6%, difference = 5%; 95% CI = 0.45% to 9.55%; P = .033) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles. The rate of breast-conserving surgery was similar in both arms (67.5% vs 68.5%, respectively, P = .68). Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles. Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles. However, they also had more toxic effects. So far, eight cycles of TAC cannot be recommended for the whole group of patients responding to two initial cycles of TAC.
Mitochondrial DNA Diversity in South America and the Genetic History of Andean Highlanders
Authors: Silvia Fuselli, Eduardo Tarazona-Santos, Isabelle Dupanloup, Alonso Soto, Donata Luiselli, Davide Pettener
Journal: Molecular Biology and Evolution (2003)

We analyzed mtDNA sequence variation in 590 individuals from 18 south Amerindian populations. The spatial pattern of mtDNA diversity in these populations fits well the model proposed on the basis of Y-chromosome data. We found evidence of a differential action of genetic drift and gene flow in western and eastern populations, which has led to genetic divergence in the latter but not in the former. Although it is not possible to identify a pattern of genetic variation common to all South America, when western and eastern populations are analyzed separately, the mtDNA diversity in both regions fits the isolation-by-distance model, suggesting independent evolutionary dynamics. Maximum-likelihood estimates of divergence times between central and south Amerindian populations fall between 13,000 and 19,000 years, which is consistent with a Pleistocenic peopling of South America. Moreover, comparison of among-population variability of mtDNA and Y-chromosome DNA seems to indicate that South America is the only continent where the levels of differentiation are similar for maternal and paternal lineages.
The need for medical education reform: genomics and the changing nature of health information
Authors: Elizabeth A Nelson, Amy L McGuire
Journal: Genome Medicine (2010)

No course in genetics can prepare the practicing physician to interpret whole-genome data. We argue that genetics is a microcosm of the changing dynamics of the practice of medicine. It illustrates the perfect storm of exponential increases in raw data with undetermined clinical relevance, ease of access to large amounts of data via the internet and shifting expectations of the doctor-patient relationship and the very mechanisms of health care delivery. Educational reform is needed across the continuum of medical education, from the student to the faculty training them, and requires a shift in focus from factual knowledge to data management and interpretation.
A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate
Authors: Mark C Genovese, Eric Lee, Julie Satterwhite, Melissa Veenhuizen, Damon Disch, Pierre-Yves Berclaz, Stephen Myers, Gregory Sides, Olivier Benichou
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the dose-response relationship, efficacy and safety of tabalumab, a human monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX). <h3>Methods</h3> In this phase 2, 24-week, double-blind, placebo-controlled, dose-ranging study, patients with RA (N=158) on stable &nbsp;MTX were randomised by Bayesian-adaptive method to receive 1, 3, 10, 30, 60, or 120 mg tabalumab or placebo subcutaneously every 4 weeks for 24 weeks. The primary objective was to test for a significant dose-response relationship using a statistical model of the proportion of patients having ≥50% improvement in American College of Rheumatology (ACR) criteria (ACR50) at week 24 (prespecified α=0.10). <h3>Results</h3> At week 24, a significant dose-response relationship was observed using ACR50 (p=0.059) and ACR20 (p=0.044) response rates. Using model-estimated data, only 120 mg had significantly higher ACR50 and ACR20 response rates versus placebo (p&lt;0.05). Observed response rates were significantly higher for 120 mg versus placebo as measured by ACR50 at weeks 12 (p=0.039) and 20 (p=0.018), but not week 24, and by ACR20 at weeks 12 (p=0.011) and 24 (p=0.039). Mean DAS28 C-reactive protein &nbsp;improved with 120 mg at week 24 (p=0.048). Frequency of TEAEs was similar across groups (range 50–69%, p=0.884). Ten (8.2%) tabalumab and 5 (13.9%) placebo patients reported a serious adverse event (SAE). Infections occurred more frequently in patients exposed to tabalumab (30.3% vs 19.4%). Serious infections were reported in 3 (2.5%) tabalumab-treated patients only. <h3>Conclusions</h3> A dose-response relationship was detected with monthly subcutaneous tabalumab. A significant effect was detected with the 120 mg dose with no unexpected safety signals. <h3>Clinical Trial #</h3> NCT00785928.
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Authors: Jiangbin Ye, Jing Fan, Sriram Venneti, Ying-Wooi Wan, Bruce R. Pawel, Ji Zhang, Lydia W.S. Finley, Chao Lu, Tullia Lindsten, Justin R. Cross, Guoliang Qing, Zhandong Liu, M. Celeste Simon, Joshua D. Rabinowitz, Craig B. Thompson
Journal: Cancer Discovery (2014)

The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in MYC-dependent cells reduced cellular NADPH:NADP+ ratio, increased cellular reactive oxygen species, and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In MYC-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and hypoxia-inducible factor-1 α (HIF1α), and SHMT2 expression correlated with unfavorable patient prognosis. Together, these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival.In this study, we demonstrate that the mitochondrial enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth.
Corrections
Authors: G Banffi, M Krajewska, G Melegati, M Patacchini
Journal: British Journal of Sports Medicine (2008)

Whole-body cryotherapy is a treatment used for various conditions, especially rheumatological disease.1 In sports medicine, whole-body cryotherapy is known to encourage recovery from muscular traumas, although well-controlled studies have not been published. The treatment is not dangerous for lung function2 and does not decrease antioxidant capacity.3

In whole-body cryotherapy, the subjects, wearing minimal clothing, are exposed to very cold air: a period of 30 seconds at –60°C and, later, a period of 2 minutes at –110°C. Despite the high cold …