tbuckley/cabot-search huggingface dataset:
Impact of overnight sleep on resting metabolic rate in OSA patients and controls
Authors: Katalin Fekete, Afroditi Boutou, Nikolaos Chavouzis, Athanasia Pataka, Georgia Pitsiou, Ioanna Athanasiou, Theodoros Kontakiotis, Paraskevi Argyropoulou, Ioannis Kioumis
Journal: European Respiratory Journal (2014)

Introduction  Obstructive sleep apnea (OSA) syndrome has been previously associated with sympathetic overactivity, hormonal dysregulation and metabolic abnormalities.  Aim  To investigate the potential variation of resting metabolic rate (RMR) just before and after an overnight sleep, in patients with OSA and in non-OSA controls.  Material-Methods  This is a nested case-control study. From a consecutive population referred for sleep evaluation between June 2007 and December 2011, subjects with OSA constituted the group of patients and subjects without OSA or other sleep disorders, the group of controls. All patients underwent anthropometric measurements, night polysomnography and evaluation of resting metabolic rate (RMR) before and after nocturnal sleep. RMR was compared before and after sleep in each group utilizing paired t-test or Wilcoxon signed rank test, according to distribution of values; level of p>0.05 was considered significant.  Results  The study population constituted of 158 OSA patients (58.2% male; 46.7±12.2 years old) and 20 controls (90% male; 51.3±11.7 years old). In OSA patients RMR measured before and after overnight sleep was significantly different (1869.8±869.5 vs. 1709.6±685.9, p 30/h) but not in the ones with mild (AH=5-15/h) syndrome. In controls no difference was noted in RMR before and after overnight sleep (1416.4±501.4 vs. 1344.2±565.2, p=0.279).  Conclusion  Patients with moderate or severe OSA establish a significant variation in RMR before and after overnight sleep, compared to non-OSA controls.
Longitudinal Associations Between Neighborhood Physical and Social Environments and Incident Type 2 Diabetes Mellitus
Authors: Paul J. Christine, Amy H. Auchincloss, Alain G. Bertoni, Mercedes R. Carnethon, Brisa N. Sánchez, Kari Moore, Sara D. Adar, Tamara B. Horwich, Karol E. Watson, Ana V. Diez Roux
Journal: JAMA Internal Medicine (2015)

Neighborhood environments may influence the risk for developing type 2 diabetes mellitus (T2DM), but, to our knowledge, no longitudinal study has evaluated specific neighborhood exposures.To determine whether long-term exposures to neighborhood physical and social environments, including the availability of healthy food and physical activity resources and levels of social cohesion and safety, are associated with incident T2DM during a 10-year period.We used data from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study of adults aged 45 to 84 years at baseline (July 17, 2000, through August 29, 2002). A total of 5124 participants free of T2DM at baseline underwent 5 clinical follow-up examinations from July 17, 2000, through February 4, 2012. Time-varying measurements of neighborhood healthy food and physical activity resources and social environments were linked to individual participant addresses. Neighborhood environments were measured using geographic information system (GIS)- and survey-based methods and combined into a summary score. We estimated hazard ratios (HRs) of incident T2DM associated with cumulative exposure to neighborhood resources using Cox proportional hazards regression models adjusted for age, sex, income, educational level, race/ethnicity, alcohol use, and cigarette smoking. Data were analyzed from December 15, 2013, through September 22, 2014.Incident T2DM defined as a fasting glucose level of at least 126 mg/dL or use of insulin or oral antihyperglycemics.During a median follow-up of 8.9 years (37,394 person-years), 616 of 5124 participants (12.0%) developed T2DM (crude incidence rate, 16.47 [95% CI, 15.22-17.83] per 1000 person-years). In adjusted models, a lower risk for developing T2DM was associated with greater cumulative exposure to indicators of neighborhood healthy food (12%; HR per interquartile range [IQR] increase in summary score, 0.88 [95% CI, 0.79-0.98]) and physical activity resources (21%; HR per IQR increase in summary score, 0.79 [95% CI, 0.71-0.88]), with associations driven primarily by the survey exposure measures. Neighborhood social environment was not associated with incident T2DM (HR per IQR increase in summary score, 0.96 [95% CI, 0.88-1.07]).Long-term exposure to residential environments with greater resources to support physical activity and, to a lesser extent, healthy diets was associated with a lower incidence of T2DM, although results varied by measurement method. Modifying neighborhood environments may represent a complementary, population-based approach to prevention of T2DM, although further intervention studies are needed.
Forecasting the risk of medicinal complications from the chemical therapy in patients with multi-resistant pulmonary tuberculosis
Authors: Fatima Tashpulatova
Journal: European Respiratory Journal (2011)

Objective:  Development of forecasting method for medicinal complications (MC) in patients with multi-resistant pulmonary tuberculosis (MPT).  Research methods and materials: 116 patients with MPT which were divided into two groups were examined: the 1st group– 88 patients with MC from chemocal preparations and the 2nd group – 78 patients without MC.   Results:  For each risk factor was determined risk rate (RR). Important in forecasting were such factors as intolerance to chemical preparations in the past and existence of pernicious habits (RR-1,4), length of sickness from 4 to 5 years (RR-2,25), existence of concomitant diseases (RR – 2,5), existence of fibro-cavernous pulmonary tuberculosis (RR – 1,7), biochemical changes in the liver (RR -2,9) and kidney (RR -3,7), changes in electrolyte metabolism (RR -2,2), leukocytosis (RR – 3,6), existence of lymphopenia (RR – 2,3), increase in ESR (erythrocyte sedimentation rate) to more than 40 mm/h (RR – 2,5), in the age of 30 - 40 years (RR – 1,77). According to decimal logarithm of their production maximal and minimal risk range of MC comprising the value from –9,9 up to +6,4 were determined.   Conclusion:  The developed forecasting method of MC in patients with MPT allows from the first days of sickness forecast the risk level of MC from the chemical preparations.
A note on Sattath and Tversky's, Saitou and Nei's, and Studier and Keppler's algorithms for inferring phylogenies from evolutionary distances.
Authors: O Gascuel
Journal: Molecular Biology and Evolution (1994)

Agglomerative algorithms iteratively pick a pair of taxa, create a new node that represents the cluster of these taxa, and compute a new distance matrix with reduced size where both taxa are replaced by this node. The cycle is repeated until the number of taxa becomes three (or two for rooted trees). This general scheme was first applied to additive unrooted trees by Sattath and Tversky (ADDTREE method; 1977) in the context of mathematical psychology. The neighbor-joining (NJ) method of Saitou and Nei ( 1987) widely popularized this approach in the phylogenetic study. This method is based on the minimum evolution principle and provides trees with near-minimal sum of branch-length estimates. An alternative formulation of the NJ method with reduced computational complexity was given by Studier and Keppler (SK method; 1988), while Rzhetsky and Nei ( 1992, 1993) clarified the theoretical foundation of the minimum evolution principle. Several simulations (Saitou and Nei 1987; Nei 199 1) have shown a high relative efficiency of ADDTREE and of the NJ method in recovering the true topology. These studies have also shown that ADDTREE and the NJ method, whose principles seem very different, are in fact close and usually provide identical or similar trees. For example, they obtain the same tree with Case’s ( 1978) data. The explanation for this proximity was given by Saitou and Nei ( 1987) for four taxa. In this note, we account for this proximity regardless of the number of taxa, and we show that the minimum evolution principle, as employed in the NJ method, is very close to the neighborliness used by Sattath and Tversky ( 1977) and by Fitch ( 198 1) in a nonagglomerative way. In the following, we recall the principles of the ADDTREE, NJ, and SK methods and explain why they are so close. We will only be concerned with the construction of the tree shape, and not with branch-lengths estimation. For the latter aspect, we refer the reader to the original papers and to
Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options
Authors: Wilbert P. Vermeij, Jan H.J. Hoeijmakers, Joris Pothof
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology.
Lottery has Orwellian resonances
Authors: T D I. Cartmill
Journal: BMJ (1995)

EDITOR,--The fact that the National Lottery collects disproportionate amounts of money from poor people would not have surprised George Orwell. In his novel Nineteen Eighty-Four he describes the effect of a lottery on the “proles,” the non-party members who constituted 85% of Oceania's population.

The …
Final report of Radiation Therapy Oncology Group (RTOG) protocol 9802: Radiation therapy (RT) versus RT + procarbazine, CCNU, and vincristine (PCV) chemotherapy for adult low-grade glioma (LGG)
Authors: E. G. Shaw, M. Wang, S. Coons, D. Brachman, J. C. Buckner, K. Stelzer, G. Barger, P. D. Brown, M. R. Gilbert, M. P. Mehta
Journal: Journal of Clinical Oncology (2008)

2006 Background: RTOG protocol 9402 demonstrated improvement in progression-free survival (PFS), but not overall survival (OS) for adult anaplastic oligodendroglioma (O) and oligo-astrocytoma (A) patients (pts) receiving PCV+RT versus (vs) RT alone (Cairncross, JCO 24:2707, 2006). In 1998, a similar study in adult LGG was initiated by RTOG, NCCTG, SWOG, and ECOG. Methods: Eligible criteria: age <40 years with subtotal resection/biopsy, age >40 with any extent of resection, supratentorial WHO grade II A, O, or OA. Pts were stratified by age, histology, KPS, and presence/absence of preop contrast enhancement and randomized to RT alone (54Gy/30 fractions) or RT followed by 6 cycles of standard dose PCV. Reported results include OS rate, median OS time (MOST), PFS rate, median PFS time (MPFST) and hazard ratio (HR). Per study design, survival data are compared using the modified Wilcoxon test (sensitive to early separation of survival curves). The log-rank test (sensitive to late separation of curves) was subsequently added for exploratory purposes. Results: 251 pts were accrued from 1998–2002. Median follow-up time is 5.9 years. The MOST and 5-year OS rate were not reached and 72% for RT+PCV vs 7.5 years and 63% for RT, HR 0.72 (p=0.33, log-rank p=0.13). The MPFST and 5-year PFS rate were not reached and 63% for RT+PCV vs 4.4 years and 46% with RT, HR 0.6 (p=0.06, log-rank p=0.005). Both OS and PFS were similar for pts treated with RT+PCV or RT between years 0–2. Beyond 2 years, the OS and PFS curves separated significantly, favoring PCV+RT pts. For 2 year survivors (n=211), the probability of OS for an additional 3 years was 84% with RT+PCV vs 72% with RT (p=0.03); comparable data for PFS was 74% with RT+PCV vs 52% with RT (p=0.002). The HR for RT+PCV vs RT (adjusted for histology) was 0.52 for death (p=0.02) and 0.45 for progression (p=0.0004). Conclusions: PFS but not OS were improved for adult WHO grade II LGG pts receiving RT+PCV versus RT alone. However, beyond 2 years, the addition of PCV to RT conferred both a significant OS and PFS advantage, and reduced the risk of death by 48% and progression by 55%, suggesting a delayed benefit for chemotherapy. Additional studies including 1p19q analysis are planned. No significant financial relationships to disclose.
Adenovirus-relaxin gene therapy for keloids: implication for reversing pathological fibrosis
Authors: W.J. Lee, Y.O. Kim, I.K. Choi, D.K. Rah, C-O. Yun
Journal: British Journal of Dermatology (2011)

Keloids or hypertrophic scars are pathological proliferations of the dermal skin layer resulting from excessive collagen deposition. Because the hormone relaxin (RLX) inhibits collagen synthesis and expression in stimulated fibroblasts, an adenovirus expressing RLX (dE1-RGD/lacZ/RLX) was generated.To investigate the effect of RLX-expressing adenovirus on expression of various extracellular matrix (ECM) components in primary keloid spheroids.The expression levels of type I and III collagen, fibronectin and elastin were investigated by immunohistochemistry in primary keloid spheroids transduced with the RLX-expressing adenovirus.Immunohistochemical analysis showed that expression of major ECM components (e.g. type I and III collagen, elastin and fibronectin) was markedly reduced in primary keloid spheroids transduced with dE1-RGD/lacZ/RLX.These results suggest that the antifibrotic effect of RLX-expressing adenovirus may have therapeutic effects on keloids by reversing pathological fibrosis and preventing keloid recurrence after surgical excision.
Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis
Authors: Randa Tao, Sunil Krishnan, Priya R. Bhosale, Milind M. Javle, Thomas A. Aloia, Rachna T. Shroff, Ahmed O. Kaseb, Andrew J. Bishop, Cameron W. Swanick, Eugene J. Koay, Howard D. Thames, Theodore S. Hong, Prajnan Das, Christopher H. Crane
Journal: Journal of Clinical Oncology (2015)

Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC.Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy).Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities.Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.
Angiocentric Lymphoma of the Head and Neck: Patterns of Systemic Failure After Radiation Treatment
Authors: Gwi Eon Kim, Jae Ho Cho, Woo Ick Yang, Eun Ji Chung, Chang Ok Suh, Kyung Ran Park, Won Pyo Hong, In Yong Park, Jee Sook Hahn, Jae Kyung Roh, Byung Soo Kim
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS: We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS: The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION: Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.
Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma
Authors: Smitha R. Georgy, Michael Cangkrama, Seema Srivastava, Darren Partridge, Alana Auden, Sebastian Dworkin, Catriona A. McLean, Stephen M. Jane, Charbel Darido
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:The developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway. GRHL3 is highly expressed in all tissues derived from the surface ectoderm, including the oral cavity, raising a question about its potential role in suppression of head and neck squamous cell carcinoma (HNSCC).
Dynamic hyperinflation and effects of pursed lips breathing on chest wall kinematics during exercise in patients with asthma
Authors: Guilherme Fregonezi, Janaina Dantas Pinto, Lailane Saturnino, Bruno Henrique Ferreira da Silva, Illia Nadinne, RÃªncio Florencio Bento, Fernando Augusto Lavezzo Dias, Selma Bruno, Vanessa Resqueti
Journal: European Respiratory Journal (2012)

To assess the effects of exercise on lung volumes and the influence of Pursed Lips Breathing (PBL) on operational lung volumes in asthma patients. In 14 patients, 33.9±10 years/old,FEV1%:65.7±18.6, lung volumes were assessed by opto-eletronic plethysmography.Two incremental submaximal cycling test (ISET) sets based on 3 min. rest, 1 min. unloaded pedaling and 30w increase in workload every min. during free breathing and PLB were done. We identified two patterns of changes in operational volumes at 100%max. workload in free breathing.Patients that increase End Expiratory Lung Volume (EELV) ΔEELV=0.27±0.5L and developed Dynamic Hyperinflation (DH),hyperinflators (HG,n=6) and patients that decrease EELV euvolumics (EG,n=6) ΔEELV=-1.07±0.8 L.Rib cage pulmonary (RCp) was the main responsible to increase in EELV in HG.Variation of End Inspiratory Lung Volume (ΔEILV) in HG was significantly different from EG,1.5±0.8 vs 0.31±0.4.PLB induced changes in EILV in both groups during in chest wall and RCp compartment. In abdominal compartment ΔEILV significantly increased with PLB in all moments except at 50%max. workload.PLB induced changes on EELV in RCp compartment at 100%max. workload in EG and at 50%max. workload, 1st and 2nd recovery time in HG.  Exercise induces different changes in operation lung volume in patients with asthma. PLB modulate breathing pattern and improve operational lung volumes.
ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy
Authors: Marie Morfouace, Satish Cheepala, Sadhana Jackson, Yu Fukuda, Yogesh T. Patel, Soghra Fatima, Daisuke Kawauchi, Anang A. Shelat, Clinton F. Stewart, Brian P. Sorrentino, John D. Schuetz, Martine F. Roussel
Journal: Cancer Research (2015)

While a small number of plasma membrane ABC transporters can export chemotherapeutic drugs and confer drug resistance, it is unknown whether these transporters are expressed or functional in less therapeutically tractable cancers such as Group 3 (G3) medulloblastoma. Herein we show that among this class of drug transporters, only ABCG2 was expressed at highly increased levels in human G3 medulloblastoma and a mouse model of this disease. In the mouse model, Abcg2 protein was expressed at the plasma membrane where it functioned as expected on the basis of export of prototypical substrates. By screening ABC substrates against mouse G3 medulloblastoma tumorspheres in vitro, we found that Abcg2 inhibition could potentiate responses to the clinically used drug topotecan, producing a more than 9-fold suppression of cell proliferation. Extended studies in vivo in this model confirmed that Abcg2 inhibition was sufficient to enhance antiproliferative responses to topotecan, producing a significant survival advantage compared with subjects treated with topotecan alone. Our findings offer a preclinical proof of concept for blockade of ABCG2 transporter activity as a strategy to empower chemotherapeutic responses in G3 medulloblastoma.
Effects of structured heart failure disease management on mortality and morbidity depend on patients' mood: results from the Interdisciplinary Network for Heart Failure Study
Authors: Götz Gelbrich, Stefan Störk, Sonja Kreißl‐Kemmer, Hermann Faller, Christiane Prettin, Peter U. Heuschmann, Georg Ertl, Christiane E. Angermann
Journal: European Journal of Heart Failure (2014)