tbuckley/cabot-search huggingface dataset:
The Renal Manifestations of Thyroid Disease
Authors: Laura H. Mariani, Jeffrey S. Berns
Journal: Journal of the American Society of Nephrology (2011)

Thyroid hormones influence renal development, kidney structure, renal hemodynamics, GFR, the function of many transport systems along the nephron, and sodium and water homeostasis. These effects of thyroid hormone are in part due to direct renal actions and in part are mediated by cardiovascular and systemic hemodynamic effects that influence kidney function. As a consequence, both hypothyroidism and hyperthyroidism associate with clinically important alterations in kidney function and have relevance to its assessment. Disorders of thyroid function have also been linked to development of immune-mediated glomerular injury, and alterations in thyroid hormones and thyroid hormone testing occur in patients with kidney disease.
Gene Space Dynamics During the Evolution of Aegilops tauschii, Brachypodium distachyon, Oryza sativa, and Sorghum bicolor Genomes
Authors: A. N. Massa, H. Wanjugi, K. R. Deal, K. O'Brien, F. M. You, R. Maiti, A. P. Chan, Y. Q. Gu, M. C. Luo, O. D. Anderson, P. D. Rabinowicz, J. Dvorak, K. M. Devos
Journal: Molecular Biology and Evolution (2011)

Nine different regions totaling 9.7 Mb of the 4.02 Gb Aegilops tauschii genome were sequenced using the Sanger sequencing technology and compared with orthologous Brachypodium distachyon, Oryza sativa (rice), and Sorghum bicolor (sorghum) genomic sequences. The ancestral gene content in these regions was inferred and used to estimate gene deletion and gene duplication rates along each branch of the phylogenetic tree relating the four species. The total gene number in the extant Ae. tauschii genome was estimated to be 36,371. The gene deletion and gene duplication rates and total gene numbers in the four genomes were used to estimate the total gene number in each node of the phylogenetic tree. The common ancestor of the Brachypodieae and Triticeae lineages was estimated to have had 28,558 genes, and the common ancestor of the Panicoideae, Ehrhartoideae, and Pooideae subfamilies was estimated to have had 27,152 or 28,350 genes, depending on the ancestral gene scenario. Relative to the Brachypodieae and Triticeae common ancestor, the gene number was reduced in B. distachyon by 3,026 genes and increased in Ae. tauschii by 7,813 genes. The sum of gene deletion and gene duplication rates, which reflects the rate of gene synteny loss, was correlated with the rate of structural chromosome rearrangements and was highest in the Ae. tauschii lineage and lowest in the rice lineage. The high rate of gene space evolution in the Ae. tauschii lineage accounts for the fact that, contrary to the expectations, the level of synteny between the phylogenetically more related Ae. tauschii and B. distachyon genomes is similar to the level of synteny between the Ae. tauschii genome and the genomes of the less related rice and sorghum. The ratio of gene duplication to gene deletion rates in these four grass species closely parallels both the total number of genes in a species and the overall genome size. Because the overall genome size is to a large extent a function of the repeated sequence content in a genome, we suggest that the amount and activity of repeated sequences are important factors determining the number of genes in a genome.
Experimental muscle pain during a forward lunge — the effects on knee joint dynamics and electromyographic activity
Authors: M Henriksen, T Alkjær, E B Simonsen, H Bliddal
Journal: British Journal of Sports Medicine (2008)

Objective: The purpose of this study was to investigate whether the knee joint dynamics during a forward lunge could be modulated by experimentally induced vastus medialis pain in healthy subjects. Design: Randomised cross-over study. Setting: Biomechanical movement laboratory. Participants: 20 healthy subjects were included. One subject was excluded during data collection. Intervention: The subjects performed forward lunges before, during and 20 minutes after induction of experimental quadriceps muscle pain. Muscle pain was induced using hypertonic saline (5.8%) injected intramuscularly. Isotonic saline (0.9%) was used as control. Main outcome measurements: Three-dimensional movement analyses were performed and inverse dynamics were used to calculate joint kinematics and kinetics for ankle, knee and hip joints. Electromyographic (EMG) signals of the hamstrings and quadriceps muscles were recorded. Results: During and after pain, significant decreases in knee joint dynamics and EMG recordings were observed. Conclusion: The study shows that local pain in the quadriceps is capable of modulating movements with high knee joint dynamics. The results may have implications in the management of muscle pain and prevention of injuries during activities involving the knee joint.
Redox active plasma iron in C282Y/C282Y hemochromatosis
Authors: Caroline Le Lan, Olivier Loréal, Tally Cohen, Martine Ropert, Hava Glickstein, Fabrice Lainé, Michel Pouchard, Yves Deugnier, André Le Treut, William Breuer, Z. Ioav Cabantchik, Pierre Brissot
Journal: Blood (2005)
Brain-to-Serum Lithium Ratio and Age: An In Vivo Magnetic Resonance Spectroscopy Study
Authors: Constance M. Moore, Christina M. Demopulos, Michael E. Henry, Ronald J. Steingard, Linda Zamvil, Alain Katic, Janis L. Breeze, JoEllyn C. Moore, Bruce M. Cohen, Perry F. Renshaw
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors’ goal was to determine if there is an association between brain-to-serum lithium ratios and age. METHOD: Lithium-7 magnetic resonance spectroscopy was used to measure in vivo brain lithium levels in nine children and adolescents (mean age=13.4 years, SD=3.6) and 18 adults (mean age=37.3, SD=9.1) with bipolar disorder. RESULTS: Serum and brain lithium concentrations were positively correlated. Younger subjects had lower brain-to-serum concentration ratios than adults: 0.58 (SD=0.24) versus 0.92 (SD=0.36). The brain-to-serum concentration ratio correlated positively with age. CONCLUSIONS: These observations suggest that children and adolescents may need higher maintenance serum lithium concentrations than adults to ensure that brain lithium concentrations reach therapeutic levels.
Disruption of the <i>E2</i> Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study
Authors: Stuart I. Collins, Christothea Constandinou-Williams, Kaisheng Wen, Lawrence S. Young, Sally Roberts, Paul G. Murray, Ciaran B.J. Woodman
Journal: Cancer Research (2009)

Integration of high-risk human papillomavirus (HPV) types into the host-cell genome disrupts the HPV regulatory E2 protein, resulting in a loss of negative feedback control of viral oncogene expression; this disruption has been considered a critical event in the pathogenesis of cervical neoplasia, and a potential biomarker of progressive disease. However, using serial samples taken from a cohort of young women who were recruited soon after they first had sexual intercourse, we show that disruption of the E2 gene is a common and early event in the natural history of incident cervical HPV infections. The E2 gene was significantly more likely to be disrupted in women who tested positive for HPV18 in their baseline sample than in those who tested positive for HPV16 [26% versus 58%; relative risk, 2.26; 95% confidence interval (CI), 1.38-3.71; chi(2), 9.23; 1 degree of freedom (df); P = 0.002]. Among women with an intact E2 gene in their baseline sample, the median time to first detection of E2 disruption was also shorter for those who tested positive for HPV18 than HPV16 (5.7 versus 10.9 months; hazards ratio, 1.93; 95% CI, 0.84-4.44; chi(2), 2.49; 1 df; P = 0.11). This tendency for HPV18 to integrate early, coupled with the substantial reduction in viral load in HPV18-positive samples in which E2 is disrupted, may explain why HPV18-associated disease is often reported to be characterized by minor cytologic changes, which underestimate the severity of the underlying histologic abnormality.
Understanding biology to tackle the disease: Multiple myeloma from bench to bedside, and back
Authors: Giada Bianchi, Kenneth C. Anderson
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract Answer questions and earn CME/CNE Multiple myeloma (MM) is a cancer of antibody‐producing plasma cells. The pathognomonic laboratory finding is a monoclonal immunoglobulin or free light chain in the serum and/or urine in association with bone marrow infiltration by malignant plasma cells. MM develops from a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage termed smoldering multiple myeloma (SMM), which differs from active myeloma by the absence of disease‐related end‐organ damage. Unlike MGUS and SMM, active MM requires therapy. Over the past 6 decades, major advancements in the care of MM patients have occurred, in particular, the introduction of novel agents (ie, proteasome inhibitors, immunomodulatory agents) and the implementation of hematopoietic stem cell transplantation in suitable candidates. The effectiveness and good tolerability of novel agents allowed for their combined use in induction, consolidation, and maintenance therapy, resulting in deeper and more sustained clinical response and extended progression‐free and overall survival. Previously a rapidly lethal cancer with few therapeutic options, MM is the hematologic cancer with the most novel US Food and Drug Administration‐approved drugs in the past 15 years. These advances have resulted in more frequent long‐term remissions, transforming MM into a chronic illness for many patients. CA Cancer J Clin 2014;64:422–444. © 2014 American Cancer Society.
Relation of speed of a mile run, maximum energy cost of running, and maximum oxygen consumption: a field study.
Authors: S K Das, A Dutta
Journal: British Journal of Sports Medicine (1995)

To compare the maximum energy cost of running (MECR) estimated from the speed of a mile run and the maximum oxygen consumption (VO2max) with a field step test.MECR was defined as the maximum VO2, derived from the equation VO2 = 5.3 mph + 3.9 (ml.min-1.kg-1), when the subject performs a maximal, exhausting run and attains maximum speed. The equation is based on a straight line relation between speed and VO2. In this study MECR was obtained from a mile run and was compared with VO2max by extrapolation using a step test. Both tests were performed in the field.The variation in the MECR with VO2max was within +/- 10%. It therefore appears that the speed of a mile run is a good criterion of VO2max or estimated MECR for the measurement of physical fitness, and for the selection, recruitment, and assignment of an individual in field sports.
Positions under Positive Selection--Key for Selectivity and Potency of Scorpion -Toxins
Authors: H. Weinberger, Y. Moran, D. Gordon, M. Turkov, R. Kahn, M. Gurevitz
Journal: Molecular Biology and Evolution (2009)

Alpha-neurotoxins target voltage-gated sodium channels (Na(v)s) and constitute an important component in the venom of Buthidae scorpions. These toxins are short polypeptides highly conserved in sequence and three-dimensional structure, and yet they differ greatly in activity and preference for insect and various mammalian Na(v)s. Despite extensive studies of the structure-function relationship of these toxins, only little is known about their evolution and phylogeny. Using a broad data set based on published sequences and rigorous cloning, we reconstructed a reliable phylogenetic tree of scorpion alpha-toxins and estimated the evolutionary forces involved in the diversification of their genes using maximum likelihood-based methods. Although the toxins are largely conserved, four positions were found to evolve under positive selection, of which two (10 and 18; numbered according to LqhalphaIT and Lqh2 from the Israeli yellow scorpion Leiurus quinquestriatus hebraeus) have been previously shown to affect toxin activity. The putative role of the other two positions (39 and 41) was analyzed by mutagenesis of Lqh2 and LqhalphaIT. Whereas substitution P41K in Lqh2 did not alter its activity, substitution K41P in LqhalphaIT significantly decreased the activity at insect and mammalian Na(v)s. Surprisingly, not only that substitution A39L in both toxins increased their activity by 10-fold but also LqhalphaIT(A39L) was active at the mammalian brain channel rNa(v)1.2a, which otherwise is hardly affected by LqhalphaIT, and Lqh2(A39L) was active at the insect channel, DmNa(v)1, which is almost insensitive to Lqh2. Thus, position 39 is involved not only in activity but also in toxin selectivity. Overall, this study describes evolutionary forces involved in the diversification of scorpion alpha-toxins, highlights the key role of positions under positive selection for selectivity and potency, and raises new questions as to the toxin-channel face of interaction.
Relationships Between Estimates of Adiposity, Insulin Resistance, and Nonalcoholic Fatty Liver Disease in a Large Group of Nondiabetic Korean Adults
Authors: Ki Chul Sung, Marno C. Ryan, Bum Soo Kim, Yong Kyun Cho, Byung Ik Kim, Gerald M. Reaven
Journal: Diabetes Care (2007)

Nonalcoholic fatty liver disease (NAFLD) is emerging as a major health problem in parallel with an increasing prevalence of obesity. Insulin resistance and abdominal and overall adiposity are closely associated with NAFLD; however, the interplay between them in the relationship with NAFLD is unclear, especially in nondiabetic individuals.Abdominal ultrasound, hepatitis serology, and measurements of fasting plasma insulin (FPI), lipid concentrations, overall obesity (BMI), and abdominal obesity (waist circumference) were performed in 56,249 Korean subjects.After rigorous exclusion criteria, 36,654 nondiabetic subjects (54% male) were enrolled. Subjects were divided into control (no fatty liver on ultrasound, serum alanine aminotransferase [ALT] <30 units/l [men] or <19 units/l [women]), fatty liver with normal ALT (FL-NALT), and fatty liver with a high ALT (FL-HALT) groups. After adjusting for age, BMI, and waist circumference, FPI and ratio of triglycerides to HDL cholesterol (TG/HDL-C ratio) were significantly higher in the FL-NALT than in the control group and even higher in the FL-HALT group. Odds ratios for the presence of FL-HALT with increasing quartiles of FPI and TG/HDL-C ratio were increased five- to sevenfold over those of the control group, independent of age, BMI, and waist circumference.In this large population of individuals of Korean ancestry, results indicate that while overall (BMI) and abdominal (waist circumference) overweight/obesity are associated with features of NAFLD, surrogate estimates of insulin resistance, FPI concentration, and TG/HDL-C ratio predict NAFLD independently of age, BMI, and waist circumference.
Community-Based Approaches to Controlling Childhood Asthma
Authors: Noreen M. Clark
Journal: Annual Review of Public Health (2012)

The prevalence and burden of childhood asthma remain high and are increasing. Asthma hot spot neighborhoods around the country face particular challenges in controlling the effects of the condition. Increasing attention is being paid to developing interventions that recognize the child and family as the primary managers of disease and to introducing assistance that reaches beyond the clinical care setting into the places where families live and work. A range of types of community-focused interventions has been assessed in the past decade in schools, homes, and community health clinics, and programs using electronic media and phone links have been evaluated. Stronger evidence for all these approaches is needed. However, school-based programs and community coalitions designed to bring about policy and systems changes show particular promise for achieving sustainable improvements in asthma control. Research is needed that emphasizes comparisons among proven asthma control interventions, translation of effective approaches to new settings and communities, and institutionalization of effective strategies.
Impact of Chemoradiotherapy After Disease Control With Chemotherapy in Locally Advanced Pancreatic Adenocarcinoma in GERCOR Phase II and III Studies
Authors: Florence Huguet, Thierry André, Pascal Hammel, Pascal Artru, Jacques Balosso, Frédéric Selle, Elisabeth Deniaud-Alexandre, Philippe Ruszniewski, Emmanuel Touboul, Roberto Labianca, Aimery de Gramont, Christophe Louvet
Journal: Journal of Clinical Oncology (2007)

The management of locally advanced (LA) pancreatic cancer patients remains controversial. To select patients who could benefit from chemoradiotherapy (CRT), the therapeutic strategy used by the Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) consisted of initial chemotherapy (CT) for at least 3 months. The decision to administer CRT or continue CT in nonprogressive patients was the investigator's choice.Retrospective analysis of outcome in 181 patients with LA pancreatic cancer (76 women and 105 men; mean age, 61 years; range, 37 to 85 years) enrolled onto prospective phase II and III GERCOR studies was performed to compare the survival of patients who received CRT with that of patients who continued CT alone.Median progression-free survival (PFS) and overall survival (OS) times for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients (29.3%) had metastatic disease after 3 months of CT and were not eligible for CRT. Among the 128 remaining patients (70.3%) who had no disease progression and who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas 56 (44%) continued with CT (group B). The two groups were balanced for initial characteristics (performance status, sex, age, and type of CT), as well as for induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4 months, respectively (P = .005), and the median OS times were 15.0 and 11.7 months, respectively (P = .0009).These results suggest that, after control of disease by initial CT, CRT could significantly improve survival in patients with LA pancreatic cancer compared with CT alone. A prospective phase III study is ongoing to evaluate this strategy.
“BRCAness” Syndrome in Ovarian Cancer: A Case-Control Study Describing the Clinical Features and Outcome of Patients With Epithelial Ovarian Cancer Associated With <i>BRCA1</i> and <i>BRCA2</i> Mutations
Authors: David S.P. Tan, Christian Rothermundt, Karen Thomas, Elizabeth Bancroft, Rosalind Eeles, Susan Shanley, Audrey Ardern-Jones, Andrew Norman, Stanley B. Kaye, Martin E. Gore
Journal: Journal of Clinical Oncology (2008)

We evaluated the clinical impact of germ-line BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to first and subsequent lines of chemotherapy, treatment-free interval (TFI) between each line of therapy, and overall survival (OS).Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA-positive) were selected from our database and matched (1:2) with 44 nonhereditary EOC controls (defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. All patients received primary platinum-based chemotherapy. Statistical comparisons included responses after first-, second-, and third-line treatment (chi(2)/Fisher's exact test) and median OS (Kaplan-Meier method/log-rank test).Compared with controls, BRCA-positive patients had higher overall (95.5% v 59.1%; P = .002) and complete response rates (81.8% v 43.2%; P = .004) to first line treatment, higher responses to second and third line platinum-based chemotherapy (second line, 91.7% v 40.9% [P = .004]; third line, 100% v 14.3% [P = .005]) and longer TFIs. A significant improvement in median OS in BRCA-positive patients compared with controls was observed from both time of diagnosis (8.4 v 2.9 years; P < .002) and time of first relapse (5 v 1.6 years; P < .001). BRCA status, stage, and length of first response were independent prognostic factors from time of first relapse.BRCA-positive EOC patients have better outcomes than nonhereditary EOC patients. There exists a clinical syndrome of BRCAness that includes serous histology, high response rates to first and subsequent lines of platinum-based treatment, longer TFIs between relapses, and improved OS.
Authors’ reply: Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels: are dromedary camels a reservoir for MERS-CoV?
Authors: N Nowotny, J Kolodziejek
Journal: Eurosurveillance (2014)

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Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting
Authors: Simon Wessely, Trudie Chalder, Steven Hirsch, Paul Wallace, David Wright
Journal: American Journal of Psychiatry (1996)

This study assessed relationships among psychological symptoms, past and current psychiatric disorder, functional impairment, somatic symptoms, chronic fatigue, and chronic fatigue syndrome.A prospective cohort study was followed by a nested case-control study. The subjects, aged 18-45 years, had been in primary care for either clinical viral infections or a range of other problems. Questionnaire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue. Assessments were made with questionnaires, interviews, and medical records of fatigue, somatic symptoms, psychiatric disorder, and functional impairment.Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by standardized interview (60% versus 19%) or by questionnaire (71% versus 31%). Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past. There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue. Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview (75%) or questionnaire (78%). Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder. The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder. Only postexertion malaise, muscle weakness, and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue.Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder. Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder, partly explained by high rates of current psychiatric disorder. The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress.