tbuckley/cabot-search huggingface dataset:
Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus
Authors: Vanja Sisirak, Dipyaman Ganguly, Kanako L. Lewis, Coline Couillault, Lena Tanaka, Silvia Bolland, Vivette D’Agati, Keith B. Elkon, Boris Reizis
Journal: The Journal of Experimental Medicine (2014)

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antibodies to self-nucleic acids, immune complex deposition, and tissue inflammation such as glomerulonephritis. Innate recognition of self-DNA and -RNA and the ensuing production of cytokines such as type I interferons (IFNs) contribute to SLE development. Plasmacytoid dendritic cells (pDCs) have been proposed as a source of pathogenic IFN in SLE; however, their net contribution to the disease remains unclear. We addressed this question by reducing gene dosage of the pDC-specific transcription factor E2-2 (Tcf4), which causes a specific impairment of pDC function in otherwise normal animals. We report that global or DC-specific Tcf4 haplodeficiency ameliorated SLE-like disease caused by the overexpression of the endosomal RNA sensor Tlr7. Furthermore, Tcf4 haplodeficiency in the B6.Sle1.Sle3 multigenic model of SLE nearly abolished key disease manifestations including anti-DNA antibody production and glomerulonephritis. Tcf4-haplodeficient SLE-prone animals showed a reduction of the spontaneous germinal center reaction and its associated gene expression signature. These results provide genetic evidence that pDCs are critically involved in SLE pathogenesis and autoantibody production, confirming their potential utility as therapeutic targets in the disease.
Sleep-disordered Breathing in Children
Authors: CAROLE L. MARCUS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Sleep-disordered breathing, particularly the obstructive sleep apnea syndrome, is common during childhood. Complications include neurocognitive deficits, growth failure, and pulmonary hypertension. Nevertheless, sleep-disordered breathing is often unrecognized in children. New syndromes, such as the upper airway resistance syndrome, have recently been described. Polysomnography is invaluable for the evaluation of sleep-disordered breathing. Advances in diagnosis and management can alleviate much of the morbidity previously associated with sleep-related respiratory disorders.
Preclinical study of dimebon on β-amyloid-mediated neuropathology in Alzheimer's disease
Authors: Jun Wang, Mario G Ferruzzi, Merina Varghese, Xianjuan Qian, Alice Cheng, Mathew Xie, Wei Zhao, Lap Ho, Giulio M Pasinetti
Journal: Molecular Neurodegeneration (2011)

Abstract Background Dimebon is a retired non-selective antihistamine drug currently being investigated as a therapeutic agent for the treatment of Alzheimer's disease (AD). Results from several completed clinical trials are mixed and contradictory. Proper interpretations of these clinical observations, as well as future development of dimebon in AD treatment are complicated by the lack of concrete information on the mechanisms by which dimebon might benefit AD. Results The present studies are designed specifically to assess whether dimebon might modulate β-amyloid (Aβ)-mediated responses which are central to the development and progression of AD dementia. We found that dimebon is bioavailable in the brains of mice following oral administration. AD mice chronically treated with dimebon exhibited a trend of improvement in spatial memory function without affecting the levels of total Aβ as well as soluble oligomeric Aβ in the brain. The same trend of behavior improvement is also seen in wild type animals chronically treated with dimebon. Conclusion Collectively, our preclinical studies using the TgCRND8 AD mouse model demonstrated that dimebon might have some beneficial effect in improving cognitive function independent of Alzheimer's disease-type Aβ-related mechanisms or global energy metabolism in the brain. Observations from our study and others suggesting dimebon might improve cognition in wild type mice and rats raises the possibility that dimebon might be able to benefit cognitive function in patients with other neurodegenerative disorders, such as Huntington's disease, or in the aging population. Additional studies will be necessary to clarify the mechanisms by which dimebon might directly or indirectly benefit cognitive function.
Security of infantile attachment as assessed in the “strange situation”: Its study and biological interpretation
Authors: Michael E. Lamb, Ross A. Thompson, William P. Gardner, Eric L. Charnov, David Estes
Journal: Behavioral and Brain Sciences (1984)

Abstract The Strange Situation procedure was developed by Ainsworth two decades agoas a means of assessing the security of infant-parent attachment. Users of the procedureclaim that it provides a way of determining whether the infant has developed species-appropriate adaptive behavior as a result of rearing in an evolutionary appropriate context, characterized by a sensitively responsive parent. Only when the parent behaves in the sensitive, species-appropriate fashion is the baby said to behave in the adaptive or secure fashion. Furthermore, when infants are observed repeatedly in the Strange Situation,the pattern of behavior is said to be highly similar, and this pattern is said to predict the infants' future behavior in a diverse array of contexts. After an exhaustive review of the literature, it is shown that these popular claims are empirically unsupported in their strong form, and that the interpretations in terms of biological adaptationare misguided. There is little reliable evidence about the specific dimensions of parental behavior that affect Strange Situation behavior, although there does appear to be some relationship between these constructs. Temporal stability in security of attachment ishigh only when there is stability in family and caretaking circumstances. Likewise, patterns of Strange Situation behavior only have substantial predictive validity in similarly stable families. Implications for future research and theorizing — particularly as they relate to the use of evolutionary biology in psychological theory — are discussed.
Gene doping: an overview and current implications for athletes
Authors: Toon van der Gronde, Olivier de Hon, Hidde J Haisma, Toine Pieters
Journal: British Journal of Sports Medicine (2013)

The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping, and is prohibited for competitive athletes. As yet there is no conclusive evidence that that gene doping has been practiced in sport. However, given that gene therapy techniques improve continuously, the likelihood of abuse will increase. A literature search was conducted to identify the most relevant proteins based on their current gene doping potential using articles from Pubmed, Scopus and Embase published between 2006 and 2011. The final list of selected proteins were erythropoietin, insulin-like growth factor, growth hormone, myostatin, vascular endothelial growth factor, fibroblast growth factor, endorphin and enkephalin, α actinin 3, peroxisome proliferator-activated receptor-delta (PPARδ) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C). We discuss these proteins with respect to their potential benefits, existing gene therapy experience in humans, potential risks, and chances of detection in current and future anti-doping controls. We have identified PPARδ and PEPCK-C as having high potential for abuse. But we expect that for efficiency reasons, there will be a preference for inserting gene target combinations rather than single gene doping products. This will also further complicate detection.
Douglas Henry Collins
Authors: O. Savage
Journal: Annals of the Rheumatic Diseases (1964)

<h3>ABSTRACT</h3> The skin and its microbiome are the first lines of defense against environmental stressors and pathogens. The symbiotic relationships between the host and the microbiome and within the microbiome are critical to host health. In frogs, this research area is lacking especially in the context of their skin infection with <i>Batrachochytrium dendrobatidis</i>. <i>B. dendrobatidis</i> is a major fungal skin pathogen to amphibians that has caused the extinction of hundreds of amphibian species populations. While some frog species are known susceptible to <i>B. dendrobatidis</i> infections, and others are resistant, we hypothesized that the skin microbiome of frogs plays a role in the prevention of <i>B. dendrobatidis</i> infections that is yet unknown. Therefore, in this work we have examined the bacterial and fungal skin microbiome of one species that is sensitive to <i>B. dendrobatidis</i> infections, <i>Anaxyrus boreas</i> (formerly: <i>Bufo boreas</i>), and the resistant species, <i>Xenopus laevis</i> and <i>Rhinella marina</i> (formerly: <i>Bufo marinus</i>). This was accomplished using tag-encoded FLX amplicon pyrosequencing (bTEFAP) of the 16S rRNA and ITS DNA regions. Our results showed that the bacterial and fungal skin microbiome of <i>A. boreas</i> and <i>R. marina</i> were more similar than to that of <i>X. laevis.</i> We found distinct patterns between the skin microbiome of <i>B. dendrobatidis</i> sensitive and resistant frog species. For the bacterial microbiome, the most abundant bacterial genus observed in all frog samples was <i>Microbacterium</i>. The resistant species had higher abundance in the genera <i>Pseudomonas</i>, <i>Sphingobium</i>, <i>Pedobacter</i>, <i>Variovorax</i>, <i>Morganella</i>, <i>Sphingomonas</i>, <i>Giesbergeria</i>, and <i>Agromyces</i>. In contrast, they had lower abundance of <i>Elizabethkingia</i> (formerly: <i>Flavobacterium</i>)<i>, Enterobacter</i>, <i>Ochrobactrum</i>, <i>Arthobacter</i>, <i>Stenotrophomonas</i>, <i>Shinella</i>, <i>Klebsiella</i>, <i>Aeromonas</i>, <i>Comomonas</i>, <i>Chitinophaga</i>, and <i>Rhodococcus</i>. Regarding the fungal microbiome, the resistant species showed higher abundance in the genera <i>Aspergillus</i>, <i>Cladosporium, Elaphomyces</i>, <i>Monascus</i>, <i>Tritirachium</i>, <i>Ceratostomella</i>, and <i>Claviceps</i>, while <i>Asterotremella</i>, <i>Trichosporon</i>, and <i>Malasezzia</i> genera were less represented in resistant species. We have also observed that in the resistant species, the skin microbiome had higher diversity in the fungal microbiota, but not in the bacterial microbiota. We speculate that those observed differences have implications in <i>B. dendrobatidis</i> susceptibility that are yet to be determined, possibly through competition for nutrients or the production of specific anti-fungal molecules. <h3>GRAPHICAL ABSTRACT</h3>
The spread, treatment, and prevention of HIV-1: evolution of a global pandemic
Authors: Myron S. Cohen, Nick Hellmann, Jay A. Levy, Kevin DeCock, Joep Lange
Journal: Journal of Clinical Investigation (2008)

The most up-to-date estimates demonstrate very heterogeneous spread of HIV-1, and more than 30 million people are now living with HIV-1 infection, most of them in sub-Saharan Africa. The efficiency of transmission of HIV-1 depends primarily on the concentration of the virus in the infectious host. Although treatment with antiviral agents has proven a very effective way to improve the health and survival of infected individuals, as we discuss here, the epidemic will continue to grow unless greatly improved prevention strategies can be developed and implemented. No prophylactic vaccine is on the horizon. However, several behavioral and structural strategies have made a difference--male circumcision provides substantial protection from sexually transmitted diseases, including HIV-1, and the application of antiretroviral agents for prevention holds great promise.
Urinary Schistosomiasis Treated with Sodium Antimony Tartrate--a Quantitative Evaluation
Authors: Z. Farid, S. Bassily, D. C. Kent, A. Hassan, M. F. Abdel-Wahab, J. Wissa
Journal: BMJ (1968)

Seventeen Egyptian male farm-workers aged 8 to 27 years infected with Schistosoma haematobium were given twice-weekly intravenous injections of sodium antimony tartrate in a dose of 0.5 g. (30 mg.) per 15 kg. body weight for 12 injections. Bell9s egg-count technique was used to evaluate results on 24-hour urine collections before and at 1, 4, 8, and 12 weeks after treatment. Patients were considered to be cured only when there were no eggs in the urine when examined by the filtration-staining, miracidial-hatching, and 24-hour urinesediment examination methods. At the final follow-up 14 out of 17 patients were found not to be passing eggs in the urine—an 82% cure rate. The mean reduction in egg output in the remaining three patients was 99%. These results are superior to any reported for other antimony drugs.
Low LDL Cholesterol, Albuminuria, and Statins for the Risk of Cancer in Type 2 Diabetes
Authors: Xilin Yang, Wing Yee So, Ronald C.W. Ma, Gary T.C. Ko, Alice P.S. Kong, Hailu Zhao, Andrea O.Y. Luk, Christopher W.K. Lam, Chung Shun Ho, Peter C.Y. Tong, Juliana C.N. Chan
Journal: Diabetes Care (2009)

OBJECTIVE LDL cholesterol &amp;lt;2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI &amp;gt; 0, AP &amp;gt; 0, or S &amp;gt; 1 indicates biological interaction. RESULTS In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78–4.31]) with significant biological interactions (RERI 1.05 [0.04–2.06]; AP 0.38 [0.09–0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64–5.09] and AP 0.60 [0.29–0.90]). Statin nonusers with LDL cholesterol &amp;lt;2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors. CONCLUSIONS In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment.
Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy
Authors: Jil C. Tardiff, Timothy E. Hewett, Bradley M. Palmer, Charlotte Olsson, Stephen M. Factor, Russell L. Moore, Jeffrey Robbins, Leslie A. Leinwand
Journal: Journal of Clinical Investigation (1999)

Multiple mutations in cardiac troponin T (cTnT) can cause familial hypertrophic cardiomyopathy (FHC). Patients with cTnT mutations generally exhibit mild or no ventricular hypertrophy, yet demonstrate a high frequency of early sudden death. To understand the functional basis of these phenotypes, we created transgenic mouse lines expressing 30%, 67%, and 92% of their total cTnT as a missense (R92Q) allele analogous to one found in FHC. Similar to a mouse FHC model expressing a truncated cTnT protein, the left ventricles of all R92Q lines are smaller than those of wild-type. In striking contrast to truncation mice, however, the R92Q hearts demonstrate significant induction of atrial natriuretic factor and β-myosin heavy chain transcripts, interstitial fibrosis, and mitochondrial pathology. Isolated cardiac myocytes from R92Q mice have increased basal sarcomeric activation, impaired relaxation, and shorter sarcomere lengths. Isolated working heart data are consistent, showing hypercontractility and diastolic dysfunction, both of which are common findings in patients with FHC. These mice represent the first disease model to exhibit hypercontractility, as well as a unique model system for exploring the cellular pathogenesis of FHC. The distinct phenotypes of mice with different TnT alleles suggest that the clinical heterogeneity of FHC is at least partially due to allele-specific mechanisms.
The expression of TNF alpha by human muscle. Relationship to insulin resistance.
Authors: M Saghizadeh, J M Ong, W T Garvey, R R Henry, P A Kern
Journal: Journal of Clinical Investigation (1996)

TNFalpha is orverexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp. technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF (r = -0.60, P < 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance.
No blind schizophrenics: Are NMDA-receptor dynamics involved?
Authors: Glenn S. Sanders, Steven M. Platek, Gordon G. Gallup
Journal: Behavioral and Brain Sciences (2003)

Abstract Numerous searches have failed to identify a single co-occurrence of total blindness and schizophrenia. Evidence that blindness causes loss of certain NMDA-receptor functions is balanced by reports of compensatory gains. Connections between visual and anterior cingulate NMDA-receptor systems may help to explain how blindness could protect against schizophrenia.
Long-Term Outcome of a Routine Versus Selective Invasive Strategy in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Authors: Keith A.A. Fox, Tim C. Clayton, Peter Damman, Stuart J. Pocock, Robbert J. de Winter, Jan G.P. Tijssen, Bo Lagerqvist, Lars Wallentin
Journal: Journal of the American College of Cardiology (2010)
Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease
Authors: Virginie Beauséjour Ladouceur, Patrick R. Lawler, Michelle Gurvitz, Louise Pilote, Mark J. Eisenberg, Raluca Ionescu-Ittu, Liming Guo, Ariane J. Marelli
Journal: Circulation (2015)

The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD.In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (P<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure.From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.
Outcomes of Medical Emergencies on Commercial Airline Flights
Authors: Drew C. Peterson, Christian Martin-Gill, Francis X. Guyette, Adam Z. Tobias, Catherine E. McCarthy, Scott T. Harrington, Theodore R. Delbridge, Donald M. Yealy
Journal: New England Journal of Medicine (2013)

Worldwide, 2.75 billion passengers fly on commercial airlines annually. When in-flight medical emergencies occur, access to care is limited. We describe in-flight medical emergencies and the outcomes of these events.We reviewed records of in-flight medical emergency calls from five domestic and international airlines to a physician-directed medical communications center from January 1, 2008, through October 31, 2010. We characterized the most common medical problems and the type of on-board assistance rendered. We determined the incidence of and factors associated with unscheduled aircraft diversion, transport to a hospital, and hospital admission, and we determined the incidence of death.There were 11,920 in-flight medical emergencies resulting in calls to the center (1 medical emergency per 604 flights). The most common problems were syncope or presyncope (37.4% of cases), respiratory symptoms (12.1%), and nausea or vomiting (9.5%). Physician passengers provided medical assistance in 48.1% of in-flight medical emergencies, and aircraft diversion occurred in 7.3%. Of 10,914 patients for whom postflight follow-up data were available, 25.8% were transported to a hospital by emergency-medical-service personnel, 8.6% were admitted, and 0.3% died. The most common triggers for admission were possible stroke (odds ratio, 3.36; 95% confidence interval [CI], 1.88 to 6.03), respiratory symptoms (odds ratio, 2.13; 95% CI, 1.48 to 3.06), and cardiac symptoms (odds ratio, 1.95; 95% CI, 1.37 to 2.77).Most in-flight medical emergencies were related to syncope, respiratory symptoms, or gastrointestinal symptoms, and a physician was frequently the responding medical volunteer. Few in-flight medical emergencies resulted in diversion of aircraft or death; one fourth of passengers who had an in-flight medical emergency underwent additional evaluation in a hospital. (Funded by the National Institutes of Health.).
Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition
Authors: Andrew Adey, Hilary G Morrison, None Asan, Xu Xun, Jacob O Kitzman, Emily H Turner, Bethany Stackhouse, Alexandra P MacKenzie, Nicholas C Caruccio, Xiuqing Zhang, Jay Shendure
Journal: Genome biology (2010)

Abstract We characterize and extend a highly efficient method for constructing shotgun fragment libraries in which transposase catalyzes in vitro DNA fragmentation and adaptor incorporation simultaneously. We apply this method to sequencing a human genome and find that coverage biases are comparable to those of conventional protocols. We also extend its capabilities by developing protocols for sub-nanogram library construction, exome capture from 50 ng of input DNA, PCR-free and colony PCR library construction, and 96-plex sample indexing.