tbuckley/cabot-search huggingface dataset:
Descending Pathways in Motor Control
Authors: Roger N. Lemon
Journal: Annual Review of Neuroscience (2008)

Each of the descending pathways involved in motor control has a number of anatomical, molecular, pharmacological, and neuroinformatic characteristics. They are differentially involved in motor control, a process that results from operations involving the entire motor network rather than from the brain commanding the spinal cord. A given pathway can have many functional roles. This review explores to what extent descending pathways are highly conserved across species and concludes that there are actually rather widespread species differences, for example, in the transmission of information from the corticospinal tract to upper limb motoneurons. The significance of direct, cortico-motoneuronal (CM) connections, which were discovered a little more than 50 years ago, is reassessed. I conclude that although these connections operate in parallel with other less direct linkages to motoneurons, CM influence is significant and may subserve some special functions including adaptive motor behaviors involving the distal extremities.
Class-Sparing Regimens for Initial Treatment of HIV-1 Infection
Authors: Sharon A. Riddler, Richard Haubrich, A. Gregory DiRienzo, Lynne Peeples, William G. Powderly, Karin L. Klingman, Kevin W. Garren, Tania George, James F. Rooney, Barbara Brizz, Umesh G. Lalloo, Robert L. Murphy, Susan Swindells, Diane Havlir, John W. Mellors
Journal: New England Journal of Medicine (2008)

The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].).
Shift work and vascular events: systematic review and meta-analysis
Authors: M. V. Vyas, A. X. Garg, A. V. Iansavichus, J. Costella, A. Donner, L. E. Laugsand, I. Janszky, M. Mrkobrada, G. Parraga, D. G. Hackam
Journal: BMJ (2012)

<b>Objective</b> To synthesise the association of shift work with major vascular events as reported in the literature. <b>Data sources</b> Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines. <b>Study selection</b> Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population. <b>Data extraction</b> Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, ischaemic stroke, and any coronary event. Heterogeneity was measured with the I<sup>2</sup> statistic and computed random effects models. <b>Results</b> 34 studies in 2 011 935 people were identified. Shift work was associated with myocardial infarction (risk ratio 1.23, 95% confidence interval 1.15 to 1.31; I<sup>2</sup>=0) and ischaemic stroke (1.05, 1.01 to 1.09; I<sup>2</sup>=0). Coronary events were also increased (risk ratio 1.24, 1.10 to 1.39), albeit with significant heterogeneity across studies (I<sup>2</sup>=85%). Pooled risk ratios were significant for both unadjusted analyses and analyses adjusted for risk factors. All shift work schedules with the exception of evening shifts were associated with a statistically higher risk of coronary events. Shift work was not associated with increased rates of mortality (whether vascular cause specific or overall). Presence or absence of adjustment for smoking and socioeconomic status was not a source of heterogeneity in the primary studies. 6598 myocardial infarctions, 17 359 coronary events, and 1854 ischaemic strokes occurred. On the basis of the Canadian prevalence of shift work of 32.8%, the population attributable risks related to shift work were 7.0% for myocardial infarction, 7.3% for all coronary events, and 1.6% for ischaemic stroke. <b>Conclusions</b> Shift work is associated with vascular events, which may have implications for public policy and occupational medicine.
Frequent Expansions of the Bitter Taste Receptor Gene Repertoire during Evolution of Mammals in the Euarchontoglires Clade
Authors: Takashi Hayakawa, Nami Suzuki-Hashido, Atsushi Matsui, Yasuhiro Go
Journal: Molecular Biology and Evolution (2014)

Genome studies of mammals in the superorder Euarchontoglires (a clade that comprises the orders Primates, Dermoptera, Scandentia, Rodentia, and Lagomorpha) are important for understanding the biological features of humans, particularly studies of medical model animals such as macaques and mice. Furthermore, the dynamic ecoevolutionary signatures of Euarchontoglires genomes may be discovered because many species in this clade are characterized by their successful adaptive radiation to various ecological niches. In this study, we investigated the evolutionary trajectory of bitter taste receptor genes (TAS2Rs) in 28 Euarchontoglires species based on homology searches of 39 whole-genome assemblies. The Euarchontoglires species possessed variable numbers of intact TAS2Rs, which ranged from 16 to 40, and their last common ancestor had at least 26 intact TAS2Rs. The gene tree showed that there have been at least seven lineage-specific events involving massive gene duplications. Gene duplications were particularly evident in the ancestral branches of anthropoids (the anthropoid cluster), which may have promoted the adaptive evolution of anthropoid characteristics, such as a trade-off between olfaction and other senses and the development of herbivorous characteristics. Subsequent whole-gene deletions of anthropoid cluster TAS2Rs in hominoid species suggest ongoing ectopic homologous recombination in the anthropoid cluster. These findings provide insights into the roles of adaptive sensory evolution in various ecological niches and important clues related to the molecular mechanisms that underlie taste diversity in Euarchontoglires mammalian species, including humans.
Gene therapy of hepatic diseases: prospects for the new millennium
Authors: K SHETTY
Journal: Gut (2000)

As we stand on the cusp of the 21st century, the prospect of treating liver diseases by the manipulation of genetic material seems to be not merely a remote possibility, but a tangible reality. The rapid advances in biotechnology over the past few decades have afforded a unique understanding of the molecular mechanisms underlying various hepatic disorders. As a result, novel and exciting techniques have been developed for the genetic modification of hepatocytes. In this article, we will highlight advances in particular areas, and lend perspective as to their future prospects.

### GENE AUGMENTATION THERAPY

This strategy involves administration of a normal gene to replace a missing or dysfunctional gene product resulting from a defective gene, as has been illustrated by studies on the hereditary disorder familial hypercholesterolaemia. In this disease, a defect in the low density lipoprotein (LDL) receptor gene results in abnormal expression of the LDL receptor and consequent failure of clearance of LDL cholesterol.1 Using an animal model of familial hypercholesterolaemia, the Watanabe heritable hyperlipidaemic (WHHL) rabbit, investigators have been able to show the successful transduction of a functional rabbit LDL gene into target hepatocytes. This resulted in a 30–40% reduction in serum cholesterol, with the recombinant LDL receptor being detectable for up to six months.2 In clinical trials, five patients homozygous for familial hypercholesterolaemia underwent ex vivo replacement of the faulty gene.3 This was achieved by segmental hepatic resection, preparation of hepatocyte cultures, and transduction of these cultures with a recombinant retrovirus encoding the gene for the human LDL receptor. The genetically modified cells were then transplanted into the liver using portal venous cannulation. Prolonged reductions in LDL cholesterol were seen in three of the five patients, and this procedure was remarkably free of any major side effects. This study served to demonstrate the feasibility of ex …
“Nature versus Nurture” Study of Deceased-Donor Pairs in Kidney Transplantation
Authors: Daniel W. Louvar, Na Li, Jon Snyder, Yi Peng, Bertram L. Kasiske, Ajay K. Israni
Journal: Journal of the American Society of Nephrology (2009)

Donor characteristics such as age and cause of death influence the incidence of delayed graft function (DGF) and graft survival; however, the relative influence of donor characteristics ("nature") versus transplant center characteristics ("nurture") on deceased-donor kidney transplant outcomes is unknown. We examined the risks for DGF and allograft failure within 19,461 recipient pairs of the same donor's kidneys using data from the US Renal Data System. For the 11,894 common-donor pairs transplanted at different centers, a recipient was twice as likely to develop DGF when the recipient of the contralateral kidney developed DGF (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.82 to 2.30). Similarly, for 7567 common-donor pairs transplanted at the same center, the OR for DGF was 3.02 (95% CI 2.62 to 3.48). For pairs transplanted at the same center, there was an additional 42% risk for DGF compared with pairs transplanted at different centers. After adjustment for DGF, the within-pair ORs for allograft failure by 1 yr were 1.92 (95% CI 1.33 to 2.77) and 1.77 (95% CI 1.25 to 2.52) for recipients who underwent transplantation at the same center and different centers, respectively. These data suggest that both unmeasured donor characteristics and transplant center characteristics contribute to the risk for DGF and that the former also contribute significantly to allograft failure.
Patient-Reported Outcomes in Sentinel Node–Negative Adjuvant Breast Cancer Patients Receiving Sentinel-Node Biopsy or Axillary Dissection: National Surgical Adjuvant Breast and Bowel Project Phase III Protocol B-32
Authors: Stephanie R. Land, Jacek A. Kopec, Thomas B. Julian, Ann M. Brown, Stewart J. Anderson, David N. Krag, Nicholas J. Christian, Joseph P. Costantino, Norman Wolmark, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2010)

Sentinel lymph node resection (SNR) may reduce morbidity while providing the same clinical utility as conventional axillary dissection (AD). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if SN is positive. We report the definitive patient-reported outcomes (PRO) comparisons.Eligible patients had clinically node-negative, operable invasive breast cancer. The PRO substudy included all SN-negative participants enrolled May 2001 to February 2004 at community institutions in the United States (n = 749; 78% age > or = 50; 87% clinical tumor size < or = 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year 3. Arm symptoms, arm use avoidance, activity limitations, and quality of life (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures analyses.Arm symptoms were significantly more bothersome for SNAD compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12 months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to experience ipsilateral arm and breast symptoms, restricted work and social activity, and impaired QOL (P < or = .002 all items). From 12 to 36 months, fewer than 15% of either SNAD or SNR patients reported moderate or greater severity of any given symptom or activity limitation.Arm morbidity was greater with SNAD than with SNR. Despite considerable fears about complications from AD for breast cancer, this study demonstrates that initial problems with either surgery resolve over time.
Combining Population Health and Baseline Risk Strategy by Determining an Age Cutoff for Initiating Statins in Patients With Diabetes
Authors: Sajith Siyambalapitiya, Uditha Bulugahapitiya, Jabulani Sithole, Soon Song, Devaka J.S. Fernando, Iskandar Idris
Journal: Diabetes Care (2007)

Strategies for initiating statin use among adult patients with diabetes for primary cardiovascular disease (CVD) prevention include treating all patients (assuming diabetes is a coronary risk equivalent) or treating patients who are at risk of developing CVD. The aim of the study was to combine both strategies to derive an appropriate age cutoff for prescribing statins. By considering different strategies, we also aim to assess the effectiveness and efficiency of different strategies to reduce CVD events.This was a cross-sectional primary care population study using electronic patient files from 304 general practitioner practices in England and Wales. Of 60,258 patients with diabetes, 11,005 men and women aged 30-74 years fullfilled criteria for primary CVD prevention. Model outcomes were extrapolated to an estimated national diabetes prevalence of 3.6%.The age transition from a low-risk to a moderate-risk category for diabetic men and women occurred at ages 40.6 and 44.2 years, respectively, and sensitivity and specificity for fulfilling moderate CVD risk criteria were 97.9 and 61.8% for men and 92.0 and 77.0% for women. When applied to the national population, the age cutoff strategies were an effective and efficient strategy, potentially avoiding 11,094 events with a number needed to treat of 25.1.A strategy to treat all men and women with diabetes aged >40 and 45 years, respectively, with statins showed good compromise between high effectiveness and high efficiency for reducing CVD events. Strategy to intervene if cholesterol was >5 mmol/l was the least effective and efficient in preventing CVD events.
Penetrating Chest Wounds
Authors: D. E. Dickson
Journal: BMJ (1940)

MEDICAL JOURNAL deltoid muscle three inches below the shoulder, and be found lodged in the crest of the left ilium, and yet no serious damage was done to the chest, the abdomen, or either kidney.Repair of Vessels and Nerves In this war there should be a much higher percentage of suture of arteries and nerves.Every effort must be made to repair and preserve main arteries and nerves. 'IA.draw over cut en-d of arer prlmnr to eoa.2heIn G.h usleofl heparin Carrel's maethd it imperative that Govranmoentcut once tfarter stpreiinr tohaemor it poTicedei csuatay clearesing pstation, shoulda vese atriangula threadedre.prepatred for imeodtiatge use, vsmall curved roated staigh neles (No.ntinuous suture,trog and forpcalso vsuture (vsuchned Japanese silk.Twuseheemnineer).sat
LKB1 loss promotes endometrial cancer progression via CCL2-dependent macrophage recruitment
Authors: Christopher G. Peña, Yuji Nakada, Hatice D. Saatcioglu, Gina M. Aloisio, Ileana Cuevas, Song Zhang, David S. Miller, Jayanthi S. Lea, Kwok-Kin Wong, Ralph J. DeBerardinis, Antonio L. Amelio, Rolf A. Brekken, Diego H. Castrillon
Journal: Journal of Clinical Investigation (2015)

Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women. For most patients in whom the disease is confined to the uterus, treatment results in successful remission; however, there are no curative treatments for tumors that have progressed beyond the uterus. The serine/threonine kinase LKB1 has been identified as a potent suppressor of uterine cancer, but the biological modes of action of LKB1 in this context remain incompletely understood. Here, we have shown that LKB1 suppresses tumor progression by altering gene expression in the tumor microenvironment. We determined that LKB1 inactivation results in abnormal, cell-autonomous production of the inflammatory cytokine chemokine (C-C motif) ligand 2 (CCL2) within tumors, which leads to increased recruitment of macrophages with prominent tumor-promoting activities. Inactivation of Ccl2 in an Lkb1-driven mouse model of endometrial cancer slowed tumor progression and increased survival. In human primary endometrial cancers, loss of LKB1 protein was strongly associated with increased CCL2 expression by tumor cells as well as increased macrophage density in the tumor microenvironment. These data demonstrate that CCL2 is a potent effector of LKB1 loss in endometrial cancer, creating potential avenues for therapeutic opportunities.
Effects of theophylline, dexamethasone and salbutamol on cytokine gene expression in human peripheral blood CD4+ T-cells
Authors: DK Choy, F Ko, ST Li, LS lp, R Leung, D Hui, KN Lai, CK Lai
Journal: European Respiratory Journal (1999)

CD4+ T-cells are considered as pivotal in orchestrating the airway inflammation in asthma through the actions of their cytokines. Current hypothesis suggests that the anti-asthma effect of theophylline may be due to its anti-inflammatory actions, although the exact mechanisms remain unclear. The in vitro effect of theophylline on cytokine gene expression in peripheral blood CD4+ T-cells in normal subjects was compared with that of dexamethasone and salbutamol. CD4+ T-cells were cultured with phytohaemagglutin and phorbol myristate acetate in the presence of different concentrations of theophylline (10(-8)-10(-3) M or 0.0018-180 microg x mL(-1)) in one group of subjects (n=8), dexamethasone (10(-9)-10(-6) M or 0.39-390 ng x mL(-1)) in a second group (n=8) and salbutamol (10(-9)-10(-4) M or 0.00058-58 microg x mL(-1)) in a third group (n=8). Gene expression of interleukin (IL)-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-gamma was semiquantified by reverse transcription-polymerase chain reaction. Suppressed expression of IL-3 (36.9%), IL4 (38.8%), GM-CSF (24.6%) and IFN-gamma (37.7%), but not of IL-5, was only seen with theophylline at a concentration of 10(-3) M (180 microg x mL(-1)) (p<0.05) and not at lower concentrations. In contrast, dexamethasone caused a dose-dependent suppression of transcription of all cytokines, with 39.5% for IL-3, 84.4% for IL-4, 40.6% for IL-5, 50.9% for GM-CSF and 31.8% for IFN-gamma at 10(-6) M (390 ng x mL(-1)) (p<0.05-0.001). Salbutamol did not suppress gene expression of any of the cytokines at the concentrations examined. These data suggest that cytokine gene expression of CD4+ T-cells is not affected at therapeutic concentrations of theophylline and salbutamol, but its suppression is likely to be an important mechanism underlying the therapeutic effect of corticosteroids in asthma.
Fine Structure of Transplantable Hepatomas of the Rat2
Authors: Zdenek Hruban, Hewson Swift, Miloslav Rechcigl
Journal: JNCI Journal of the National Cancer Institute (1965)

The fine structure of 6 hepatomas representing wide variability in rates of growth has been investigated. These include 2 fast-growing tumors, Novikoff and Morris 3683, 2 ethionine-induced tumors with intermediate growth rates, and 2 slow-growing tumors, Reuber H-35 and Morris 5123. The fine structure of each hepatoma is characteristic. Common to all hepatomas are large nucleoli, a large Golgi complex, and the presence of numerous free ribosomes arranged in clusters. The fast-growing hepatomas have a simple organization of the cytoplasm. The slow-growing hepatomas have better developed and more organized cytoplasmic membrane systems, including well-developed rough and smooth endoplasmic reticulum. Stacks of rough cisternae are-best developed in the slow-growing Reuber H-35 hepatoma. Mitochondria are smaller and have fewer cristae in the rapidly growing hepatomas and are larger and more hepatocyte-like in the slow-growing tumors. Nevertheless, the structure of slow-growing hepatomas never resembles that of normal hepatocytes in complexity. It is suggested that major differences between hepatomas can be attributed to three factors: growth rate of the tissue, its genetic and developmental history, and, indirectly, to nutritional factors and tumorhost relationship.
Magnetic resonance imaging of male and female genitals during coitus and female sexual arousal
Authors: W. W. Schultz, P. van Andel, I. Sabelis, E. Mooyaart
Journal: BMJ (1999)

To find out whether taking images of the male and female genitals during coitus is feasible and to find out whether former and current ideas about the anatomy during sexual intercourse and during female sexual arousal are based on assumptions or on facts.Observational study.University hospital in the Netherlands.Magnetic resonance imaging was used to study the female sexual response and the male and female genitals during coitus. Thirteen experiments were performed with eight couples and three single women.The images obtained showed that during intercourse in the "missionary position" the penis has the shape of a boomerang and 1/3 of its length consists of the root of the penis. During female sexual arousal without intercourse the uterus was raised and the anterior vaginal wall lengthened. The size of the uterus did not increase during sexual arousal.Taking magnetic resonance images of the male and female genitals during coitus is feasible and contributes to understanding of anatomy.
Pulmonary Hypertension Due to Left Heart Diseases
Authors: Jean-Luc Vachiéry, Yochai Adir, Joan Albert Barberà, Hunter Champion, John Gerard Coghlan, Vincent Cottin, Teresa De Marco, Nazzareno Galiè, Stefano Ghio, J. Simon R. Gibbs, Fernando Martinez, Marc Semigran, Gerald Simonneau, Athol Wells, Werner Seeger
Journal: Journal of the American College of Cardiology (2013)