tbuckley/cabot-search huggingface dataset:
Congenital Central Hypoventilation Syndrome
Authors: Elizabeth M. Berry-Kravis, Lili Zhou, Casey M. Rand, Debra E. Weese-Mayer
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases.Objectives: To characterize CCHS-associated nonpolyalanine repeat mutations in PHOX2B, evaluate genotype–phenotype relationships, and compare clinical features of CCHS in cases with nonpolyalanine repeat mutations to those with polyalanine expansion mutations.Methods: DNA from probands was analyzed by polymerase chain reaction for the common polyalanine repeat expansion. If no expansion was present, coding regions and intron–exon boundaries of PHOX2B were sequenced. When possible, parents and siblings were screened for the mutation found in the proband.Results: Fourteen nonpolyalanine repeat mutations, including missense, nonsense, and frameshift mutations, and 170 polyalanine repeat mutations were identified in 184 CCHS probands. Both incomplete penetrance and parental mosaicism were observed within the family members of probands with nonpolyalanine repeat mutations. Increased prevalence of continuous ventilatory dependence, HSCR, and neural crest tumors was seen in the nonpolyalanine repeat group compared to those with polyalanine repeat mutations.Conclusions: These data suggest that nonpolyalanine repeat mutations produce more severe disruption of PHOX2B function. Patients carrying these mutations should be evaluated for HSCR and neural crest tumors. Because incomplete penetrance can occur in families of CCHS probands with PHOX2B mutations, genetic screening of appropriate family members is indicated to evaluate reproductive risk and because asymptomatic mutation carriers may be at risk for developing alveolar hypoventilation.
Adaptive Landscapes of Resistance Genes Change as Antibiotic Concentrations Change
Authors: Portia M Mira, Juan C Meza, Anna Nandipati, Miriam Barlow
Journal: Molecular Biology and Evolution (2015)

Most studies on the evolution of antibiotic resistance are focused on selection for resistance at lethal antibiotic concentrations, which has allowed the detection of mutant strains that show strong phenotypic traits. However, solely focusing on lethal concentrations of antibiotics narrowly limits our perspective of antibiotic resistance evolution. New high-resolution competition assays have shown that resistant bacteria are selected at relatively low concentrations of antibiotics. This finding is important because sublethal concentrations of antibiotics are found widely in patients undergoing antibiotic therapies, and in nonmedical conditions such as wastewater treatment plants, and food and water used in agriculture and farming. To understand the impacts of sublethal concentrations on selection, we measured 30 adaptive landscapes for a set of TEM β-lactamases containing all combinations of the four amino acid substitutions that exist in TEM-50 for 15 β-lactam antibiotics at multiple concentrations. We found that there are many evolutionary pathways within this collection of landscapes that lead to nearly every TEM-genotype that we studied. While it is known that the pathways change depending on the type of β-lactam, this study demonstrates that the landscapes including fitness optima also change dramatically as the concentrations of antibiotics change. Based on these results we conclude that the presence of multiple concentrations of β-lactams in an environment result in many different adaptive landscapes through which pathways to nearly every genotype are available. Ultimately this may increase the diversity of genotypes in microbial populations.
Canadian academic’s call for moratorium on HPV vaccine sparks controversy
Authors: Owen Dyer
Journal: BMJ (2015)

Canada’s human papillomavirus vaccination program should be halted immediately until its safety can be established, a researcher who has studied patient experiences of the vaccine under a government grant has said.

Genevieve Rail, a professor of critical studies of health at Montreal’s Concordia University, has a $C273 359 (£135 000; €185 000; $208 000) grant from the Canadian Institutes of Health Research for research entitled “HPV vaccination discourses, spaces and biopedagogies: Affects and effects on youth’s bodies and subjectivities.” She reports having gathered 170 families whose recounted stories indicate a heavy burden of vaccine injury.

Writing in the Quebec daily newspaper Le Devoir , Rail and her coauthor Abby Lippman, a former professor in McGill University’s department of epidemiology, biostatistics, and occupational health, argued that the vaccine was given to schoolgirls without obtaining proper informed consent.1 They said that it had caused serious adverse events around the world, that Canada’s system of reporting was inadequate to detect problems, that it was a misplaced priority because cervical cancer was not a leading cause of death, that its efficacy was not proven, that it may even exacerbate precancerous lesions, and that it was fraudulently marketed and too hastily approved.

“Across the world,” the authors wrote, “young vaccinated girls are the protagonists in a drama of which only the pharmaceutical companies know the …
Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment
Authors: Andrea Ponzetta, Giorgia Benigni, Fabrizio Antonangeli, Giuseppe Sciumè, Emilio Sanseviero, Alessandra Zingoni, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Angela Santoni, Giovanni Bernardini
Journal: Cancer Research (2015)

Abstract Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1− NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1− NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma–bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma–promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth. Cancer Res; 75(22); 4766–77. ©2015 AACR.
Antituberculosis Activity of Once-weekly Rifapentine-containing Regimens in Mice
Authors: NATHALIE DANIEL, NACER LOUNIS, BAOHONG JI, RICHARD J. O'BRIEN, ANDREW VERNON, LAWRENCE J. GEITER, MICHEL SZPYTMA, CHANTAL TRUFFOT-PERNOT, GILLES HEJBLUM, JACQUES GROSSET
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 × 106 colony-forming units (cfu) of Mycobacterium tuberculosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin (S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ + 6-mo HE were rendered spleen and lung culture–negative at 6 mo and 8 mo, respectively. Treatment failure with emergence of R-resistant bacilli occurred in all mice given once-weekly monotherapy with P for 6 mo. Once-weekly PH treatment was successful at 6 mo when it was preceded by a 2-mo daily phase with HRZ. When the initial daily phase was reduced to 2 wk, once-weekly PH-containing treatment was successful, at 6 mo, only if it was supplemented with S during the initial daily and the once-weekly phases, and at 8 mo if it was supplemented with daily H during the once-weekly phase. Without these supplements, once-weekly treatment failed in some mice with selection of R-resistant or H-resistant mutants.
LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells
Authors: Hwan-Jin Hwang, Tae Woo Jung, Ho Cheol Hong, Ji A. Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dong Seop Choi, Sei Hyun Baik, Hye Jin Yoo
Journal: Metabolism (2015)
Death after cardiac surgery is chiefly due to patient risk factors, study finds
Authors: Susan Mayor
Journal: BMJ (2015)

<h3>Objective</h3> The objectives of this study were to determine the proportion of smokers registered at the quit smoking clinic at a public hospital in northeastern Malaysia who successfully quit smoking and the predictive factors for successfully quitting smoking. <h3>Methods</h3> This was a cross-sectional study involving smokers aged more than 18 years old and registered with the clinic from January 1, 2012, to October 31, 2014. Data were obtained with a designed questionnaire that consisted of sociodemographic information, medical history, smoking characteristics, and type of treatment received by smokers. Smokers who quit smoking 6 months after being registered at the quit smoking clinic were considered as successful quitters. Multiple logistic regression was applied to determine the predictive factors for successfully quitting smoking. <h3>Results</h3> From a total of 202 respondents, 42.6% [95% confidence interval (CI) 35.8–49.4%] of them successfully quit smoking. Multiple logistic regression showed that the number of cigarettes smoked per day (adjusted odds ratio 2.51, 95% CI 1.17–5.41) and a previous quit attempt (adjusted odds ratio 1.88, 95% CI 1.03–3.44) were significant predictors for successfully quitting smoking. <h3>Conclusion</h3> This study shows that the proportion of smokers who successfully quit smoking among smokers registered at the quit smoking clinic was relatively high. A number of cigarettes smoked per day of 20 or fewer and a previous quit attempt significantly predict successful quitting of smoking. <h3>Significance statement</h3> Cigarette smoking is one of the risk factors leading to noncommunicable diseases such as cardiovascular and respiratory system diseases and cancer. Quitting smoking is difficult for many people and may involve multiple attempts. A quit smoking clinic is designed to assist smokers with tobacco dependence to quit smoking. There are many factors that contribute to successfully quitting smoking. The present study found that from a total of 202 respondents who attended the clinic, 42.6% of them successfully quit smoking. In addition, the number of cigarettes smoked per day and a previous quit attempt were significant predictors for successfully quitting smoking. These findings should be taken into consideration in interventions for smokers who wish to quit smoking.
Second Cancers Occurring in Patients With Early Stage Non–Small-Cell Lung Cancer Treated With Chest Radiation Therapy Alone
Authors: Branislav Jeremic, Yuta Shibamoto, Ljubisa Acimovic, Nebojsa Nikolic, Aleksandar Dagovic, Jasna Aleksandrovic, Gordana Radosavljevic-Asic
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the incidence of second cancers occurring in patients with early stage (I/II) non–small-cell lung cancer (NSCLC) treated with radiation therapy (RT) alone. PATIENTS AND METHODS: Seventy-eight patients had been treated with conventionally fractionated (CF) RT (1982 to 1987), and 116 patients had been treated with hyperfractionated (Hfx) RT (1988 to 1993). Tumor doses were 60 Gy for CF and 69.6 Gy (1.2 Gy bid) for Hfx. RESULTS: A total of 26 patients developed second cancers. The cumulative incidence of second cancer was 21.8% (SE, 4.7%) at 5 years and 34.8% (SE, 6.7%) at 10 years. For second lung cancers, it was 6.0% (SE, 2.8%) at 5 years and 14.2% (SE, 5.2%) at 10 years, and for second nonlung cancers, it was 16.3% (SE, 4.2%) at 5 years and 22.2% (SE, 5.7%) at 10 years. The rate of developing second cancer per patient per year was 4.3% (95% confidence intervals [CI], 2.7% to 5.9%), with the rates being 1.4% (CI, 0.5% to 2.3%) for the second lung cancers and 2.8% (CI, 1.5% to 4.1%) for second nonlung cancers. The rate of developing second cancers during the first and second 5-year period after RT (0 to 5 and 5 to 10 years) was 4.3% (CI, 2.4% to 6.2%) and 4.2% (CI, 0.6% to 7.8%), respectively, for all cancers. These rates were 1.0% (CI, 0.1% to 1.9%) and 2.2% (CI, 0% to 4.6%), respectively, for second lung cancers, and 3.2% (CI, 1.6% to 4.8%) and 1.5% (CI, 0% to 3.6%), respectively, for second nonlung cancers. CONCLUSION: Long-term survivors after RT alone for early stage NSCLC carry the same risk of developing second cancer, either lung or nonlung, as their counterparts treated surgically when the results of this study are compared with those of the published literature.
Prognostic Performance of Multiple Biomarkers in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Authors: Ryan G O'Malley, Marc P Bonaca, Benjamin M Scirica, Sabina A Murphy, Petr Jarolim, Marc S Sabatine, Eugene Braunwald, David A Morrow
Journal: Journal of the American College of Cardiology (2014)
Methodologic Lessons Learned From Hot Flash Studies
Authors: Jeff A. Sloan, Charles L. Loprinzi, Paul J. Novotny, Debra L. Barton, Beth I. Lavasseur, Harold Windschitl
Journal: Journal of Clinical Oncology (2001)

PURPOSE: In the course of conducting a series of prospective clinical trials devoted to defining new treatment opportunities for hot flashes in cancer survivors, considerable experience has been acquired with related methodologic issues. This article has been written in response to many queries regarding this methodology. PATIENTS AND METHODS: A series of seven different clinical trials that involved 968 patients was used for this work. Reliable and valid definitions of hot flash intensity were developed from patient-reported descriptions. Concomitant validity and reliability assessment of patient-completed diaries was undertaken to compare hot flash data with toxicity and quality-of-life (QOL) end points and to examine consistency across patient groups using variability analysis and correlation procedures. Parametric data from this meta-analysis was used to examine relative power considerations for the design of phase II and phase III clinical trials. RESULTS: Daily diaries used in these studies exhibited consistency and reliability and had few missing data. Hot flash frequency and hot flash score (frequency multiplied by average severity) variables produced almost identical end point results. For phase III placebo-controlled studies, 50 patients per treatment arm seem appropriate to provide sufficient power specifications to detect a clinically meaningful change in hot flash activity. For phase II trials, 25 patients per trial seem to provide reasonable estimates of eventual hot flash efficacy to screen potential agents for more definitive testing. CONCLUSION: Given the data gained from these experiences, we can plan and carry out more efficient trials to identify efficacious agents for the reduction of hot flash activity.
Manage growing demand: Respiratory nurse clinic keeps people with COPD healthy
Authors: Shu Wah Steve Ng, Wai Yee Tsang, Chung Leung Henry Poon, Lee Veronica Chan, Chung Ming Chu
Journal: European Respiratory Journal (2011)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) was ranked second as a respiratory cause of hospitalization (14.6%) and inpatient bed-days (20.5%) among common respiratory diseases in Hong Kong. A pilot of Respiratory Nurse Clinic for COPD has been implemented since December 2009 in United Christian Hospital in Hong Kong. It focused on reducing the need for intensive medical care for COPD patients. This preliminary review aims to evaluate the effectiveness of the clinic.

Methodology: The Respiratory Nurse Clinic for COPD was run by qualified Respiratory Nurses and accredited locally since December 2009. Confirmed COPD patients who were high risk of hospitalization could be recruited. The key components of the program included patient registry, risk stratification, different models/levels of care with holistic approach, home non-invasive ventilator program, patient empowerment program and 24-hours hotline service.

Results: The first 100 COPD patients were analyzed for their healthcare utilization for three months before and after joining the clinic. Their mean age was 74.6±7.26. More than 90% of them were severe or very severe COPD. It was statistically significant showing that the number of emergency department attendance was reduced by 40.07% from 5.39 to 3.23 times (p<0.001). Also, the total numbers of unplanned admission and the length of stay were reduced by 44.5% from 1.91 to 1.06 (p<0.001) times and 49.5% from 5.81 to 3.05 days (p<0.001) respectively. The mean Modified Borg Scale was reduced from 2.88 to 2.02 (p<0.001).

Conclusions: The Respiratory Nurse Clinic could significantly reduce the healthcare utilization of the COPD patients and control their symptom.
Decreased Interleukin-15 From Activated Cord Versus Adult Peripheral Blood Mononuclear Cells and the Effect of Interleukin-15 in Upregulating Antitumor Immune Activity and Cytokine Production in Cord Blood
Authors: John X. Qian, Sun min Lee, Yu Suen, Eva Knoppel, Carmella van de Ven, Mitchell S. Cairo
Journal: Blood (1997)
Ten Million and One. Neurological Disability as a National Problem.
Authors: Eric Denhoff
Journal: Annals of Internal Medicine (1958)

This monograph summarizes the results of the Conference on Neurological Disability as a National Problem held at Arden House, Harriman, New York, in December, 1955. It was attended by more than 50 highly qualified specialists with various interests in the field who met to explore the realistic possibilities of meeting the problems posed by more than 10 million patients suffering from more than 300 clinical entities loosely grouped together as "neurologic disabilities." Neurologic disabilities are defined as those disorders which are associated demonstrably with dysfunction, disease, or injury of the nervous system, the brain, the spinal cord, and the peripheral neuromuscular connections.
An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme1
Authors: Abdeljabar El Andaloussi, Maciej S. Lesniak
Journal: Neuro-Oncology (2006)

The subpopulation of CD4+CD25+ immunoregulatory T (Tr) cells constitutes 5%-10% of CD4+ cells in humans. These cells play a crucial role in the control of tumor immune response. In this study, we evaluated the distribution of Tr cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme and examined the difference between the brain and autologous blood with respect to Tr cells. Glioma samples from 10 patients were classified as WHO grade IV astrocytoma. Control samples were obtained from patients undergoing resection of a seizure focus. The samples were analyzed by flow cytometry to determine the frequency of Tr cells and by real-time PCR for forkhead box P3 (FOXP3) expression. We then examined the expression of CD62L, CD45RO, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and assessed the functionality of Tr cells in vitro. There was a significant difference in the number of FOXP3-expressing CD4+CD25+ T cells within glioma-infiltrating lymphocytes as compared to controls (P < 0.01). This difference was further observed in studies of autologous patient blood and control blood. The expression level of FOXP3 mRNA was high in Tr cells and weak in CD4+CD25-T cells. Moreover, the expression of CD62L and CTLA-4 was elevated in glioma Tr cells as compared to that in the controls. These cells were also CD45RO positive. Functional assays confirmed the suppressive activity of Tr cells in patients with glioma. The expression of CD4+CD25+FOXP3+ T cells was significantly higher in patients with glioblastoma multiforme than in controls. This increase in the frequency of Tr cells that display suppressive activity might play a role in modulation of the immune response against glioma. In light of these findings, Tr cells may represent a potential target for immunotherapy of malignant brain tumors.
Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib
Authors: Clare Sun, Xin Tian, Yuh Shan Lee, Sreenivasulu Gunti, Andrew Lipsky, Sarah E. M. Herman, Dalia Salem, Maryalice Stetler-Stevenson, Constance Yuan, Lela Kardava, Susan Moir, Irina Maric, Janet Valdez, Susan Soto, Gerald E. Marti, Mohammed Z. Farooqui, Abner L. Notkins, Adrian Wiestner, Georg Aue
Journal: Blood (2015)
Low-Dose Guar Improves Diabetic Control
Authors: D B Jones, S Lousley, R Jelfs, P Slaughter, R D Carter, J I Mann
Journal: Journal of the Royal Society of Medicine (1985)

Twenty diabetic outpatients (12 non-insulin-treated and 8 insulin-treated) were given guar granulate in a dose of 10 g daily for two months in order to study the effect on glycaemic control and lipid levels. Mean glycosylated haemoglobin levels (HbAlc%) fell from 11.1±2.0% pre-guar to 10.5 ± 2.2% (P&lt; 0.001) after one month on guar and to 10.1±2.3% ( P&lt;0.0001) after two months. Following discontinuation of guar, HbAlc% rose to 11.1±2.5% ( P&lt;0.002). However, there were no significant changes in fasting blood glucose, 1 h postprandial blood glucose following a test meal, 24 h urinary glucose excretion or in lipid levels. Gastrointestinal side effects occurred in 4 patients during treatment with guar. Four patients reduced their dose of insulin and 2 patients reduced their dose of sulphonylurea therapy during this time because of symptoms suggestive of hypoglycaemia. We suggest that the low dose of guar used in this study may help improve glycaemic control in diabetic patients and that this may be achieved with a low incidence of gastrointestinal side effects.