tbuckley/cabot-search huggingface dataset:
Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response
Authors: David P. Kao, James D. Lewsey, Inder S. Anand, Barry M. Massie, Michael R. Zile, Peter E. Carson, Robert S. McKelvie, Michel Komajda, John JV McMurray, JoAnn Lindenfeld
Journal: European Journal of Heart Failure (2015)
Induction of anterior chamber-associated immune deviation requires an intact, functional spleen.
Authors: J W Streilein, J Y Niederkorn
Journal: The Journal of Experimental Medicine (1981)

Anterior chamber-associated immune deviation (ACAID) expresses itself in BALB/c mice inoculated intracamerally with P815 cells in three ways: progressive growth of the tumor within the eye, transient growth of P815 cells injected subcutaneously, and prolonged acceptance of DBA/2 skin allografts. The spleen was found to play a crucial role in the development of ACAID. Splenectomized animals bearing intracameral P815 tumors reject DBA/2 skin grafts in an accelerated manner. A functioning spleen was required during the first 10 d after intracameral inoculation of P815 cells, but not thereafter. Reconstitution experiments revealed that the spleen's ability to support the induction of ACAID depends partly upon its constituent lymphoid cells, but also upon either a stromal component or a unique architectural arrangement that can only be restored with splenic fragments. The data hold promise that therapeutic protocols using appropriately timed splenectomy and specific immunization can be devised to induce hosts bearing intraocular tumors to mount an immune response sufficiently vigorous to destroy the tumor within the eye, and sufficiently precise to preserve the functional and anatomic integrity of the eye.
Taking folate in pregnancy and risk of maternal breast cancer
Authors: Deborah Charles, Andy R Ness, Doris Campbell, George Davey Smith, Marion H Hall
Journal: BMJ (2004)

Taking folate before conception and then for the first three months of pregnancy reduces the risk of recurrence of neural tube defects, 1 and fortification of food has been proposed.The effects of long term exposure to high concentrations of supplemental folate are unknown, and antimetabolite effects are theoretically possible. 2Data on the long term effects of increased folate intake in pregnancy are limited.We followed up a large trial of folate supplementation in pregnancy from the 1960s. 3 4 We examined the association between folate status and death, and we also analysed the effects of folate supplementation. Participants, methods, and resultsFrom June 1966 to June 1967, 3187 women were identified as potentially eligible for a trial of folate supplementation. 3 4At her booking visit, the mother's age, gestation, parity, weight, and blood pressure were recorded, and blood was taken to measure serum folate concentrations.Tablets were supplied in six colours, two of which contained folate in 0.2 mg and 5 mg daily doses.The tablets were kept in numbered drawers and distributed in sequence.The trial was double blind.The husband or partner's occupation at the time of delivery was used to determine social class.Linking the trial data What this paper suggestsWomen taking high doses of folate throughout pregnancy may be more likely to die from breast cancer in later life than women taking no folate What research is needed nowThis may be a chance finding, so further studies should examine the association between folate supplementation in pregnancy and risk of breast cancer Papers
Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis: Table 1–
Authors: Devasahayam J. Christopher, Samuel G. Schumacher, Joy S. Michael, Robert Luo, Thangakunam Balamugesh, Paramasivan Duraikannan, Nira R. Pollock, Madhukar Pai, Claudia M. Denkinger
Journal: European Respiratory Journal (2013)

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosisTo the Editor:Tuberculosis (TB) remains the second leading cause of death from an infectious disease in adults.Extrapulmonary TB (EPTB) accounts for about 25% of all cases of active TB.Pleural TB is the second most common manifestation of EPTB.Existing tests for the diagnosis of pleural TB have major limitations in terms of accuracy, time to diagnosis and drug resistance testing, and require special expertise for sample acquisition and interpretation of the results.Biopsy of the pleural tissue for combined histological examination and culture is considered the diagnostic gold standard, albeit imperfect [1, 2].
Glomerular Complement Components in Human Glomerulonephritis
Authors: Pierre J. Verroust, Curtis B. Wilson, Neil R. Cooper, Thomas S. Edgington, Frank J. Dixon
Journal: Journal of Clinical Investigation (1974)

154 of 255 individual human renal biopsies studied by immunofluorescence contained varying combinations of immunoglobulins (Ig), complement (C) components C1q, C3, C4, C5, C6, C8, C3 proactivator (C3PA), and/or properdin. 10 patients had linear deposits of Ig in glomeruli characteristic of antiglomerular basement membrane (GBM) antibodies; nine patients had C3 deposits (minimal in three) with generally lesser amounts of C1q, C4, C5, C6, and/or C8. 118 of the patients had granular deposits of Ig, suggesting immune complex glomerulonephritis; 114 of these had deposits of C3, usually accompanied by C1q, C4, C5, and/or C6. These observations indicate that the entire C sequence is deposited in glomeruli in most Ig-mediated glomerulonephritides. However, certain cases of anti-GBM glomerulonephritis with few or no C deposits may utilize pathways of injury independent of C.21 patients had granular C3 deposits without detectable Ig. C5, C6, and C8 were present in the majority of these patients while C1q was absent and scant C4 was observed in only two patients. The presence of only late-acting C components in the absence of Ig, C1q, and C4 suggests selective, possible nonimmune activation of the alternate C pathway. Finally, five patients had granular deposits of C3, C5, C6, and/or C8 diffusely in all or most glomeruli with a lesser number of glomeruli having additional focal granular deposits of Ig, C1q, and C4. This observation suggests that at least two patterns of C activation can occur simulatenously, possibly triggered by antecedent immune complex deposition and then perpetuated by an as yet undetermined mechanism.
Tissue Enzyme Changes in Parabiotic Rats With Subcutaneous Lymphoma or Fibrosarcoma 2 3
Authors: Annemarie Herzfeld, Olga Greengard, Shields Warren
Journal: JNCI Journal of the National Cancer Institute (1978)

A solid lymphoma implanted into normal inbred Kx rats and one partner of parabiotic pairs caused appreciable decreases in hepatic ornithine aminotransferase and arginase about a week earlier (4-S days aHer implantation) in single hosts than in parabiotic hosts. By 18–21 days significant decreases in both enzymes were apparent in the host partner also. The hepatic thymidine kinase showed a fivefold elevation in single hosts 4 days aHer implantation; by 14 days its levels were about 200 times above normal and had also risen in the parabiotic hosts (20-fold) and host partners (fourfold). Implantation of fibrosarcoma caused qualitatively similar but generally less pronounced changes in these three enzymes in livers of single hosts, parabiotic hosts, and host partners. The splenic thymidine kinase 14 days aHer implantation was increased from control levels of about 3 U/g to 50.S, 44.8, and 13.5 Ulg in single hosts, parabiotic hosts, and host partners, respectively. At later stages, 17–20 days aHer implantation of the lymphoma, appreciable amounts of thymidine kinase appeared in the plasma: The units of activity per milliliter were 6.2 in single hosts, 0.79 in parabiotic hosts, and 0.55 in host partners (control <0.05). Our observations on the changes in hepatic and splenic enzymes in parabiotic rats suggest that effects of neoplasms on distant host tissues are mediated by humoral factors. The less pronounced responses in parabiotic than in single hosts indicate that the tumor-free partner affords some “protection” against these systemic effects.
The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group
Authors: J. R. Le Gall
Journal: JAMA (1996)

To develop an objective method for assessing organ dysfunction among intensive care unit (ICU) patients on the first day of the ICU stay.Physiological variables defined dysfunction in 6 organ systems. Logistic regression techniques were used to determine severity levels and relative weights for the Logistic Organ Dysfunction (LOD) score and for conversion of the LOD score to a probability of mortality.A total of 13 152 consecutive admission to 137 adult medical/surgical ICUs in 12 countries from the European/North American Study of Severity Systems.Patient vital status at hospital discharge.The LOD System identified from 1 to 3 levels of organ dysfunction for 6 organ systems: neurologic, cardiovascular, renal, pulmonary, hematologic, and hepatic. From 1 to 5 LOD points were assigned to the levels of severity, and the resulting LOD scores ranged from 0 to 22 points. Model calibration was very good in the developmental and validation samples (P=.21 and P=.50, respectively), as was model discrimination (area under the receiver operating characteristic curves of 0.843 and 0.850, respectively).The LOD System provides an objective tool for assessing severity levels for organ dysfunction in the ICU, a critical component in the conduct of clinical trials. Neurologic, cardiovascular, and renal dysfunction were the most severe organ dysfunctions, followed by pulmonary and hematologic dysfunction, with hepatic dysfunction the least severe. The LOD System takes into account both the relative severity among organ systems and the degree of severity within an organ system.
LEFT MAIN CORONARY ARTERY ST-ELEVATION MYOCARDIAL INFARCTION: CLINICAL CHARACTERISTICS AND OUTCOMES FROM A MULTICENTER REGISTRY
Authors: Khung Keong Yeo, Gagan Singh, Kelvin Chua, Jonathan Yap, Ehrin Armstrong, Stephen W. Waldo, Krishan Soni, Gregory Barsness, Jamie McCabe, Ehtisham Mahmud, David Muller, Jason Rogers, Aaron Wong, Kendrick Shunk
Journal: Journal of the American College of Cardiology (2014)
Altered Functional Connectivity in Frontal Lobe Circuits Is Associated with Variation in the Autism Risk Gene <i>CNTNAP2</i>
Authors: Ashley A. Scott-Van Zeeland, Brett S. Abrahams, Ana I. Alvarez-Retuerto, Lisa I. Sonnenblick, Jeffrey D. Rudie, Dara Ghahremani, Jeanette A. Mumford, Russell A. Poldrack, Mirella Dapretto, Daniel H. Geschwind, Susan Y. Bookheimer
Journal: Science Translational Medicine (2010)

Children who carry one variant of a brain protein associated with autism exhibit fewer long-range connections between the prefrontal cortex and more posterior brain regions.
TDP-43 knockdown impairs neurite outgrowth dependent on its target histone deacetylase 6
Authors: Fabienne C Fiesel, Christine Schurr, Stephanie S Weber, Philipp J Kahle
Journal: Molecular Neurodegeneration (2011)

Trans-activation response element (TAR) DNA binding protein of 43kDa (TDP-43) is causally related to the neurodegenerative diseases frontotemporal dementia and amyotrophic lateral sclerosis being the hallmark protein in the disease-characteristic neuropathological lesions and via genetic linkage. Histone deacetylase 6 (HDAC6) is an established target of the RNA-binding protein TDP-43. HDAC6 is an unusual cytosolic deacetylase enzyme, central for a variety of pivotal cellular functions including aggregating protein turnover, microtubular dynamics and filopodia formation. All these functions are important in the context of neurodegenerative proteinopathies involving TDP-43. We have previously shown in a human embryonic kidney cell line that TDP-43 knockdown significantly impairs the removal of a toxic, aggregating polyQ ataxin-3 fusion protein in an HDAC6-dependent manner. Here we investigated the influence of TDP-43 and its target HDAC6 on neurite outgrowth.Human neuroblastoma SH-SY5Y cells with stably silenced TDP-43 showed a significant reduction of neurite outgrowth induced by retinoic acid and brain-derived neurotrophic factor. Re-transfection with TDP-43 as well as HDAC6 rescued retinoic acid-induced neurite outgrowth. In addition, we show that silencing of HDAC6 alone is sufficient to reduce neurite outgrowth of in vitro differentiated SH-SY5Y cells.TDP-43 deficiency leads to impairment of neurite growth in an HDAC6-dependent manner, thereby contributing to neurodegenerative events in TDP-43 diseases.
Metformin and Cancer Occurrence in Insulin-Treated Type 2 Diabetic Patients
Authors: Matteo Monami, Claudia Colombi, Daniela Balzi, Ilaria Dicembrini, Stefano Giannini, Cecilia Melani, Valentina Vitale, Desiderio Romano, Alessandro Barchielli, Niccolò Marchionni, Carlo Maria Rotella, Edoardo Mannucci
Journal: Diabetes Care (2010)

Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort.During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25-0.85], P = 0.014 and 0.75 [0.39-1.45], P = 0.40, respectively).The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.
Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data
Authors: Silke Fernandes, Elisa Sicuri, Kassoum Kayentao, Anne Maria van Eijk, Jenny Hill, Jayne Webster, Vincent Were, James Akazili, Mwayi Madanitsa, Feiko O ter Kuile, Kara Hanson
Journal: The Lancet Global Health (2015)

In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2).For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted.The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV-negative women was $6·2 per DALY averted.Our findings lend strong support to the WHO guidelines that recommend a monthly dose of IPTp-SP from the second trimester onwards.Malaria in Pregnancy Consortium and the Bill & Melinda Gates Foundation.
Systematic Review of the Effects of Shared Decision-Making on Patient Satisfaction, Treatment Adherence and Health Status
Authors: E.A.G. Joosten, L. DeFuentes-Merillas, G.H. de Weert, T. Sensky, C.P.F. van der Staak, C.A.J. de Jong
Journal: Psychotherapy and Psychosomatics (2008)

&lt;i&gt;Background:&lt;/i&gt; In the last decade, the clinician-patient relationship has become more of a partnership. There is growing interest in shared decision-making (SDM) in which the clinician and patient go through all phases of the decision-making process together, share treatment preferences, and reach an agreement on treatment choice. The purpose of this review is to determine the extent, quality, and consistency of the evidence about the effectiveness of SDM. &lt;i&gt;Method:&lt;/i&gt; This is a systematic review of randomised controlled trials (RCTs) comparing SDM interventions with non-SDM interventions. Eleven RCTs met the required criteria, and were included in this review. &lt;i&gt;Results:&lt;/i&gt; The methodological quality of the studies included in this review was high overall. Five RCTs showed no difference between SDM and control, one RCT showed no short-term effects but showed positive longer-term effects, and five RCTs reported a positive effect of SDM on outcome measures. The two studies included of people with mental healthcare problems reported a positive effect of SDM. &lt;i&gt;Conclusions:&lt;/i&gt; Despite the considerable interest in applying SDM clinically, little research regarding its effectiveness has been done to date. It has been argued that SDM is particularly suitable for long-term decisions, especially in the context of a chronic illness, and when the intervention contains more than one session. Our results show that under such circumstances, SDM can be an effective method of reaching a treatment agreement. Evidence for the effectiveness of SDM in the context of other types of decisions, or in general, is still inconclusive. Future studies of SDM should probably focus on long-term decisions.
Transcriptional Control of Early T and B Cell Developmental Choices
Authors: Ellen V. Rothenberg
Journal: Annual Review of Immunology (2014)

T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcription factor networks in which these E proteins are embedded are different both in membership and in architecture for T and B cell gene regulatory programs. These differences permit lineage commitment decisions to be made in different hierarchical orders. Furthermore, in contrast to B cell gene networks, the T cell gene network architecture for effector differentiation is sufficiently modular so that E protein inputs can be removed. Complete T cell-like effector differentiation can proceed without T cell receptor rearrangement or selection when E proteins are neutralized, yielding natural killer and other innate lymphoid cells.
Vitamin D Deficiency Induces Early Signs of Aging in Human Bone, Increasing the Risk of Fracture
Authors: Björn Busse, Hrishikesh A. Bale, Elizabeth A. Zimmermann, Brian Panganiban, Holly D. Barth, Alessandra Carriero, Eik Vettorazzi, Josef Zustin, Michael Hahn, Joel W. Ager, Klaus Püschel, Michael Amling, Robert O. Ritchie
Journal: Science Translational Medicine (2013)

In addition to decreasing bone mass, vitamin D deficiency causes early aging of the remaining mineralized bone and leads to severe losses in fracture resistance.
A randomized controlled comparison of the efficacy of Dead Sea salt balneophototherapy vs. narrowband ultraviolet B monotherapy for chronic plaque psoriasis
Authors: R.S. Dawe, S. Yule, H. Cameron, H. Moseley, S.H. Ibbotson, J. Ferguson
Journal: British Journal of Dermatology (2005)

Background Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy. Objectives To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis. Methods Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance. Results The mean area under the psoriasis severity–time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0·099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0·019). There was no detectable difference in times to relapse. Conclusions In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.
In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines
Authors: Franck J. Barrat, Daniel J. Cua, André Boonstra, David F. Richards, Chad Crain, Huub F. Savelkoul, René de Waal-Malefyt, Robert L. Coffman, Catherine M. Hawrylowicz, Anne O'Garra
Journal: The Journal of Experimental Medicine (2002)

We show that a combination of the immunosuppressive drugs, vitamin D3 and Dexamethasone, induced human and mouse naive CD4+ T cells to differentiate in vitro into regulatory T cells. In contrast to the previously described in vitro derived CD4+ T cells, these cells produced only interleukin (IL)-10, but no IL-5 and interferon (IFN)-γ, and furthermore retained strong proliferative capacity. The development of these IL-10–producing cells was enhanced by neutralization of the T helper type 1 (Th1)- and Th2–inducing cytokines IL-4, IL-12, and IFN-γ. These immunosuppressive drugs also induced the development of IL-10–producing T cells in the absence of antigen-presenting cells, with IL-10 acting as a positive autocrine factor for these T cells. Furthermore, nuclear factor (NF)-κB and activator protein (AP)-1 activities were inhibited in the IL-10–producing cells described here as well as key transcription factors involved in Th1 and Th2 subset differentiation. The regulatory function of these in vitro generated IL-10–producing T cells was demonstrated by their ability to prevent central nervous system inflammation, when targeted to the site of inflammation, and this function was shown to be IL-10 dependent. Generating homogeneous populations of IL-10–producing T cells in vitro will thus facilitate the use of regulatory T cells in immunotherapy.