tbuckley/cabot-search huggingface dataset:
The Genetic and Environmental Contributions to Attention Deficit Hyperactivity Disorder as Measured by the Conners’ Rating Scales—Revised
Authors: James J Hudziak, Eske M Derks, Robert R Althoff, David C Rettew, Dorret I Boomsma
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The majority of published reports on twin studies of attention deficit hyperactivity disorder (ADHD) have indicated robust additive genetic influences and unique environmental influences. These studies typically used DSM ADHD symptoms collected by telephone or interviews with mothers. The purpose of this study was to test the genetic architecture of ADHD by using the ADHD index from Conners' Rating Scales—Revised. METHOD: From the Conners' scale forms, data for the ADHD index were collected from the mothers of 1,595 7-year-old twin pairs from the Netherlands Twin Registry. Rates of ADHD diagnoses were computed by using Conners' gender- and age-specific cutoff points. Contributions from additive, dominant, unique environmental, interaction, and gender effects were computed by using gender-genetic models. RESULTS: The prevalence of ADHD across the sample of 7-year-old twin pairs was about 4% according to the mothers' reports, consistent with other reported rates of ADHD. However, using the gender norms provided with the ADHD index, the authors found slightly higher rates of ADHD in girls than previously reported. Genetic analyses yielded a model that includes genetic dominance (48%), additive genetic factors (30%), and unique environmental factors (22%). CONCLUSIONS: The ADHD index from Conners' Rating Scales—Revised identified an appropriate percentage of children across this epidemiologic twin sample as being at risk for ADHD. The results of the genetic analyses are consistent with prior reports that ADHD is predominantly influenced by genetic factors that are both dominant and additive.
Evidence of Zoonotic Transmission of<i>Cryptococcus neoformans</i>from a Pet Cockatoo to an Immunocompromised Patient
Authors: Joshua D. Nosanchuk, Shmuel Shoham, Bettina C. Fries, Daniel S. Shapiro, Stuart M. Levitz, Arturo Casadevall
Journal: Annals of Internal Medicine (2000)

Background: Although cryptococcosis has been associated with birds for almost 50 years, point sources for infection have not been identified. Objective: To document zoonotic transmission of Cryptococcus neoformans. Design: Case report. Setting: A home in Boston, Massachusetts. Patient: A 72-year-old woman who received a diagnosis of cryptococcal meningitis in November 1998. The patient, who had been taking immunosuppressant drugs since undergoing renal transplantation in 1989, owned a pet cockatoo. Measurements: Cryptococcus neoformans was isolated from the feces of the cockatoo. Isolates from excreta and from the patient were compared by using biochemical profiles, monoclonal antibody binding patterns, restriction fragment length polymorphism analysis, and karyotyping. Results: The isolates from the patient and the cockatoo had identical biochemical profiles, the same monoclonal antibody immunofluorescence patterns, and indistinguishable patterns on restriction fragment length polymorphism analysis and karyotyping. Conclusions: The indistinguishable patient and cockatoo isolates strongly suggest that the patient's infection resulted from exposure to aerosolized cockatoo excreta. Although the incidence of cryptococcal infection due to such exposure is unknown, it may be prudent to advise immunocompromised patients to avoid pet birds and avian excreta.
The health paradox of occupational and leisure-time physical activity
Authors: A Holtermann, J V Hansen, H Burr, K Søgaard, G Sjøgaard
Journal: British Journal of Sports Medicine (2011)

Background Occupational and leisure-time physical activity are considered to provide similar health benefits. The authors tested this hypothesis. Methods A representative sample of Danish employees (n=7144, 52% females) reported levels of occupational and leisure-time physical activity in 2005. Long-term sickness absence (LTSA) spells of ≥3 consecutive weeks were retrieved from a social-transfer payment register from 2005 to 2007. Results 341 men and 620 females experienced a spell of LTSA during the period. Cox analyses adjusted for age, gender, smoking, alcohol, body mass index, chronic disease, social support from immediate superior, emotional demands, social class and occupational or leisure-time physical activity showed a decreased risk for LTSA among workers with moderate (HR 0.85, CI 0.72 to 1.01) and high (HR 0.77, CI 0.62 to 0.95) leisure-time physical activity in reference to those with low leisure-time physical activity. In contrast, an increased risk for LTSA was shown among workers with moderate (HR 1.59, CI 1.35 to 1.88) and high (HR 1.84, CI 1.55 to 2.18) occupational physical activity referencing those with low occupational physical activity. Conclusion The hypothesis was rejected. In a dose–response manner, occupational physical activity increased the risk for LTSA, while leisure-time physical activity decreased the risk for LTSA. The findings indicate opposing effects of occupational and leisure-time physical activity on global health.
Potentiation of Opsonization and Phagocytosis of Streptococcus pyogenes following Growth in the Presence of Clindamycin
Authors: Curtis G. Gemmell, Phillip K. Peterson, David Schmeling, Youngki Kim, John Mathews, Lewis Wannamaker, Paul G. Quie
Journal: Journal of Clinical Investigation (1981)

Streptococcus pyogenes, bearing M-protein on its surface, resists opsonization by normal human serum and subsequent phagocytosis by human polymorphonuclear leukocytes. Previous studies have shown that M-protein positive organisms are poorly opsonized by the alternate pathway of complement. In an attempt to define further the role of the surface components of S. pyogenes in this process, we examined the ability of clindamycin, an antibiotic that inhibits protein biosynthesis, to alter bacterial opsonization.
Induction of clusterin in tubules of nephrotic rats.
Authors: R Correa-Rotter, M E Ibarra-Rubio, G Schwochau, C Cruz, J R Silkensen, J Pedraza-Chaverri, D Chmielewski, M E Rosenberg
Journal: Journal of the American Society of Nephrology (1998)

Clusterin is a glycoprotein induced after renal tubular cell injury. The purpose of this study was to examine the expression of clusterin in a disease model characterized early in its course by predominant glomerular injury. Male Wistar rats (weighing 251 +/- 16 g) were treated with puromycin aminonucleoside (PAN: 15 mg/100 g body wt, subcutaneously; n = 7) or vehicle (control; n = 8). The kidneys were harvested 6 d after treatment, when rats were nephrotic. Clusterin mRNA was markedly induced in the kidneys of nephrotic rats (8.5-fold versus control). Immunohistochemistry studies demonstrated clusterin primarily in tubules in the cortex and medulla. Many of the tubules staining for clusterin were dilated but had no other differentiating morphologic features. Increased numbers of proliferating tubular cells were seen at 6 d, but there was no correlation between these cells and clusterin staining. In contrast to the extent and pattern of clusterin staining, vimentin was seen in only sporadic, dilated tubules, in addition to its expected glomerular localization. An increase in clusterin mRNA was not seen 1, 2, or 4 d after PAN injection. In conclusion, tubular epithelial cell induction of clusterin occurs in the kidneys of nephrotic rats. The appearance of clusterin precedes the development of tubulointerstitial disease and may be a response to the proteinuria.
Randomised controlled trials in Africa of HIV and AIDS: descriptive study and spatial distribution
Authors: Nandi Siegfried, Mike Clarke, Jimmy Volmink
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To identify and describe randomised controlled trials on HIV and AIDS conducted in Africa and to map their spatial distribution using exact geographic coordinates. <b>Design</b> Construction and analysis of a database of trials conducted wholly or partly in Africa and reported before 2004. <b>Data sources</b> CENTRAL, Medline, Embase, and LILACS. <b>Results</b> Our comprehensive search yielded 284 distinct records that were potentially eligible for inclusion in the database. Of these, 150 articles reported on 77 eligible trials published or reported from 1987 to 2003. Seven trials were identified exclusively from the CENTRAL database. Trials were conducted in 18 of 48 countries in sub-Saharan Africa. None were conducted in north Africa. Only 19 had a principal investigator located in an African country. Forty two trials assessed prevention and 35 assessed treatment. Most studies were funded by government agencies outside Africa (n = 43), with the pharmaceutical industry providing partial support to 16 of these. The pharmaceutical industry provided full or partial support to a further 18 trials. Only 43 trials reported conducting a power calculation for determining sample size. There was no mention of ethical approval or informed consent in 19 and 17 trials, respectively. <b>Conclusion</b> The relatively small number of HIV/AIDS trials conducted in Africa is not commensurate with the burden of disease. Geographical mapping as an adjunct to prospective trial registration is a useful tool for researchers and decision makers to track existing and future trials.
In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions
Authors: Christodoulos Xinaris, Valentina Benedetti, Paola Rizzo, Mauro Abbate, Daniela Corna, Nadia Azzollini, Sara Conti, Mathieu Unbekandt, Jamie A. Davies, Marina Morigi, Ariela Benigni, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2012)

The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.
Radiofrequency Ablation With or Without Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial
Authors: Zhen-Wei Peng, Yao-Jun Zhang, Min-Shan Chen, Li Xu, Hui-Hong Liang, Xiao-Jun Lin, Rong-Ping Guo, Ya-Qi Zhang, Wan Yee Lau
Journal: Journal of Clinical Oncology (2012)

Purpose To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Patients and Methods A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Results At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. Conclusion TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.
Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia
Authors: Justine E. Roderick, Gabriela Gonzalez-Perez, Christina Arieta Kuksin, Anushka Dongre, Emily R. Roberts, Janani Srinivasan, Chester Andrzejewski, Abdul H. Fauq, Todd E. Golde, Lucio Miele, Lisa M. Minter
Journal: The Journal of Experimental Medicine (2013)

Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progression remain ill defined. The NOTCH signaling pathway mediates Th1 cell differentiation in the presence of polarizing cytokines, an action requiring enzymatic processing of NOTCH receptors by γ-secretase. Using a mouse model of AA, we demonstrate that expression of both intracellular NOTCH1IC and T-BET, a key transcription factor regulating Th1 cell differentiation, was increased in spleen and BM-infiltrating T cells during active disease. Conditionally deleting Notch1 or administering γ-secretase inhibitors (GSIs) in vivo attenuated disease and rescued mice from lethal BMF. In peripheral T cells from patients with untreated AA, NOTCH1IC was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET. Treating patient cells with GSIs in vitro lowered NOTCH1IC levels, decreased NOTCH1 detectable at the TBX21 promoter, and decreased T-BET expression, indicating that NOTCH1 signaling is responsive to GSIs during active disease. Collectively, these results identify NOTCH signaling as a primary driver of Th1-mediated pathogenesis in AA and may represent a novel target for therapeutic intervention.
Hydrogen Sulfide-Induced Hypometabolism Prevents Renal Ischemia/Reperfusion Injury
Authors: Eelke M. Bos, Henri G.D. Leuvenink, Pauline M. Snijder, Niels J. Kloosterhuis, Jan-Luuk Hillebrands, Jaklien C. Leemans, Sandrine Florquin, Harry van Goor
Journal: Journal of the American Society of Nephrology (2009)

Hydrogen sulfide (H(2)S) can induce a hypometabolic, hibernation-like state in mammals when given in subtoxic concentrations. Pharmacologically reducing the demand for oxygen is a promising strategy to minimize unavoidable hypoxia-induced injury such as ischemia/reperfusion injury during renal transplantation. Here we show that H(2)S reduces metabolism in vivo, ex vivo, and in vitro. Furthermore, we demonstrate the beneficial effects of H(2)S-induced hypometabolism in a model of bilateral renal ischemia/reperfusion injury using three different treatment strategies. The results demonstrate striking protective effects on survival, renal function, apoptosis, and inflammation. A hypometabolic state induced by H(2)S might have therapeutic potential to protect kidneys that suffer from hypoxia.
Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors
Authors: Masakazu Imamura, Sadatoshi Biro, Takashi Kihara, Shiro Yoshifuku, Kunitsugu Takasaki, Yutaka Otsuji, Shinichi Minagoe, Yoshifumi Toyama, Chuwa Tei
Journal: Journal of the American College of Cardiology (2001)
TLR4 Promotes Fibrosis but Attenuates Tubular Damage in Progressive Renal Injury
Authors: Wilco P. Pulskens, Elena Rampanelli, Gwendoline J. Teske, Loes M. Butter, Nike Claessen, Ilse K. Luirink, Tom van der Poll, Sandrine Florquin, Jaklien C. Leemans
Journal: Journal of the American Society of Nephrology (2010)

Toll-like receptors (TLRs) can orchestrate an inflammatory response upon activation by pathogen-associated motifs and release of endogenous stress ligands during tissue injury. The kidney constitutively expresses most TLRs, including TLR4. The function of TLR4 during the inflammation, tubular atrophy, and fibrosis that accompany progressive renal injury is unknown. Here, we subjected wild-type (WT) and TLR4-deficient mice to unilateral ureteral obstruction and observed elevated levels of TLR4 mRNA in the kidney after obstruction. One day after unilateral ureteral obstruction, TLR4-deficient mice had fewer proliferating tubular epithelial cells and more tubular damage than WT mice; however, TLR4-deficient mice developed considerably less renal fibrosis despite decreased matrix metalloproteinase activity and without significant differences in myofibroblast accumulation. In vitro, TLR4-deficient primary tubular epithelial cells and myofibroblasts produced significantly less type I collagen mRNA after TGF-beta stimulation than WT cells. The reduced fibrosis in TLR4-deficient mice associated with an upregulation of Bambi, a negative regulator of TGF-beta signaling. In conclusion, TLR4 attenuates tubular damage but promotes renal fibrosis by modulating the susceptibility of renal cells to TGF-beta. These data suggest that TLR4 signaling may be a therapeutic target for the prevention of renal fibrosis.
The Use of Gene-Expression Profiling to Identify Candidate Genes in Human Sepsis
Authors: Benjamin M P Tang, Anthony S McLean, Ian W Dawes, Stephen J Huang, Ruby C Y Lin
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Our understanding of the pathophysiology of sepsis remains incomplete. Genomewide study offers an unbiased, system biology approach to examine the expression patterns of circulating leukocytes and may reveal novel insights into the host response to sepsis.Objectives: We examined whether gene-expression profiling of neutrophils could identify signature genes and important pathways in the clinical syndrome of sepsis.Methods: Gene-expression profiling was performed using oligonucleotide microarrays on peripheral blood samples of 94 critically ill patients (71 septic and 23 nonseptic). Using a supervised learning algorithm based on support vector machine, a molecular signature of sepsis was generated from a training set of 44 samples and validated in an independent set of 50 samples. The diagnostic performance of the signature genes was assessed against a reference standard based on the International Sepsis Forum Consensus Conference definition of infection.Measurements and Main Results: A set of 50 signature genes correctly identified sepsis with a prediction accuracy of 91 and 88% in the training and validation sets, respectively. The diagnostic performance remained high regardless of patient's age, comorbidities, or prior antibiotic treatment. Compared with controls, genes involved in immune modulation and inflammatory response had reduced expression in patients with sepsis. In particular, the activation of nuclear factor-κB pathway was reduced, whereas its inhibitor gene, NFKBIA, was significantly up-regulated.Conclusions: The signature genes reflect suppression of neutrophils' immune and inflammatory function by sepsis. Gene-expression profiling therefore provides a novel approach to advance our understanding of the host response in sepsis.
High-mobility group box 1 protein (HMGB1) in ischaemic heart disease: beneficial or deleterious?
Authors: M. Takahashi
Journal: Cardiovascular Research (2008)

High-mobility group box 1 (HMGB1; also known as amphoterin) protein was identified more than 30 years ago as a non-chromosomal nuclear protein that maintains the nucleosome structure and regulates gene transcription.1 HMGB1 is highly conserved among species, has over 98% identity among all mammals, and is ubiquitously expressed in almost all types of cells. HMGB1-deficient mice are viable but die shortly after birth due to hypoglycaemia, suggesting that its nuclear functions are essential for survival. In 1999, Wang et al. 2 discovered that HMGB1 functions as a delayed mediator in inflammatory responses in sepsis and showed that the inhibition of HMGB1 confers significant protection against the lethal effects of endotoxin, indicating the importance of extracellular HMGB1 in inflammation.

HMGB1 is released into the extracellular milieu by two different routes: passive release from necrotic cells and active secretion from activated innate immune cells such as monocytes and macrophages. In necrotic cells, HMGB1 leaks into the extracellular environment via disrupted plasma membranes. In contrast, apoptotic cells retain chromatin-bound HMGB1. Therefore, HMGB1 is thought to contribute to the inflammation elicited by necrosis. Active secretion of HMGB1 from monocytes or macrophages occurs in response to proinflammatory stimuli, such as lipopolysaccharide, tumour necrosis factor-α, and interleukin-1β. HMGB1 has been reported to transduce its signals by interacting with at least three receptors: receptor for advanced glycation end products (RAGE), Toll-like receptor-2 (TLR2), and TLR4. RAGE signalling … 

Corresponding author. Tel: +81 263 37 3352; fax: +81 263 37 2573. E-mail address: masafumi{at}shinshu-u.ac.jp
Risk-Adjusted Surgical Outcomes
Authors: Jennifer Daley, William G. Henderson, Shukri F. Khuri
Journal: Annual Review of Medicine (2001)

▪ Abstract Measures of risk-adjusted outcome are particularly suited for the assessment of the quality of surgical care. The reliability of measures of quality that use surgical outcomes is enhanced by prospective data acquisition and should be adjusted for the preoperative severity of illness. Such measures should be based only on reliable and validated data, and they should apply state-of-the-art analytical methods. The risk-adjusted postoperative mortality rate is useful as a quality measure only in specialties and operations expected to have a high rate of postoperative deaths. Risk-adjusted complications are more common but are limited as a comparative measure of quality by a lack of uniform definitions and data collection mechanisms. In specialties in which the expected postoperative mortality is low, risk-adjusted functional outcomes are promising measures for the assessment of the quality of surgical care. Measures of cost and patient satisfaction should also be incorporated in systems designed to measure the quality and cost-effectiveness of surgical care.
Incidence of Endophthalmitis after Corneal Transplant or Cataract Surgery in a Medicare Population
Authors: Dongyi (Tony) Du, Austin Wagoner, Samuel B. Barone, Craig E. Zinderman, Jeffrey A. Kelman, Thomas E. MaCurdy, Richard A. Forshee, Chris M. Worrall, Hector S. Izurieta
Journal: Ophthalmology (2013)