tbuckley/cabot-search huggingface dataset:
Doctors in New York "pill mill" worked under daily threats, court hears
Authors: O. Dyer
Journal: BMJ (2015)

Apraclonidine and pilocarpine have been shown to be effective in reducing the incidence of intraocular pressure (IOP) spikes following argon laser trabeculoplasty. An additional reduction in the incidence of acute pressure rise might theoretically be expected by combining these two effective agents. In a prospective randomised study we compared the ability of apraclonidine and pilocarpine alone and in combination to prevent post laser pressure spikes. Patients receiving regular pilocarpine to either eye were excluded. Seventy five eyes received either apraclonidine (26 eyes), pilocarpine (23 eyes), or both drugs (26 eyes). Apraclonidine 1% was instilled 1 hour before and immediately after, and pilocarpine 4% immediately after trabeculoplasty. IOP was measured before and at 1, 2, and 3 hours following trabeculoplasty. In only two (8%) eyes receiving combined treatment was a pressure rise observed. This frequency was significantly lower than that seen in eyes treated with apraclonidine alone (38%), or pilocarpine alone (39%). The mean fall in IOP at 1, 2, and 3 hours was significantly greater in those eyes receiving combined treatment than in the other two groups.
Primary Prevention With Statins
Authors: Martin B. Mortensen, Shoaib Afzal, Børge G. Nordestgaard, Erling Falk
Journal: Journal of the American College of Cardiology (2015)

Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. This study compared these approaches in a direct head-to-head fashion in a contemporary population. The study used the CGPS (Copenhagen General Population Study) with 37,892 subjects aged 40 to 75 years recruited in 2003 to 2008, all free of ASCVD, diabetes, and statin use at baseline. Among the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC/AHA risk-based approach, the net reclassification index for eligibility for statin therapy among 40- to 75-year-old subjects from the CGPS was –0.21 for the trial-based approach and –0.13 for the hybrid approach. The clinical performance of the ACC/AHA risk-based approach for primary prevention of ASCVD with statins was superior to the trial-based and hybrid approaches. Our results indicate that the ACC/AHA guidelines will prevent more ASCVD events than the trial-based and hybrid approaches, while treating fewer people compared with the trial-based approach.
Design and development of high-drug-load paclitaxel (PTX)-antibody conjugates: Synthesis and preliminary evaluation of soluble paclitaxel (sPTX) and sPTX-cetuximab conjugates
Authors: A. S. Safavy, S. Quiles
Journal: Journal of Clinical Oncology (2009)

e14634 Background: Tumor cell surface receptor-targeted therapy of cancer is an effective treatment strategy and monoclonal antibody (MAb)-drug conjugates hold promise as tumor-specific drug delivery systems. We have previously reported the synthesis and biological evaluation of paclitaxel (PTX)-MAb conjugates using the anti-EGFR MAb, cetuximab, as an agent for tumor-targeted drug delivery system (Safavy et al., Bioconjugate Chem 14:302–310, 2003). One limitation of these conjugates was a low drug load, i.e., PTX : MAb ratios of ≤4, and thereby, low target dose delivery. Attempts to synthesize conjugates with PTX : MAb of &gt;4 failed due to their low water solubility. As the source of this problem was identified to be the highly lipophilic PTX moiety, we hypothesized that conjugation of water-soluble PTX analogues may lead to the preservation of the MAb solubility, and thus, to the preparation of conjugates with high PTX : MAb ratios. Methods: Newly available “discrete” poly(ethylene glycol) (dPEG) linkers were utilized for the synthesis of soluble PTX analogues. In contrast to the regular PEGs wit dispersed molecular weight ranges (MWs), the dPEGs are single-MW compounds which make possible the exact dose calculation for the resulting conjugates. Solid-phase peptide synthesis methodology was used to prepare a trifunctional dPEG-lysine (K) linker, which was first conjugated to PTX to yield the water-soluble drug analogue sPTXdPEGKdPEG, containing a free carboxylic acid group. Using the latter functionality, sPTXdPEGLysdPEG was covalently conjugated to cetuximab (C225) at increasing molar ratios. Cell binding assays were performed using MCF-7 human breast carcinoma cell line. Results: sPTXC225 conjugates with PTX : C225 ratios of up to 8 were synthesized through this method, which in contrast to the previously reported conjugates, demonstrated complete aqueous solubility. Cell binding assays indicated preservation of the immunoreactivity of the parent MAb in all conjugates. Conclusions: Water-soluble and high-drug-load PTX-MAbs such as sPTXC225, may be useful for targeted delivery of therapeutically effective doses of paclitaxel and warrant further investigation. No significant financial relationships to disclose.
The Nagasaki Atomic Bomb Survivors' Tumor Tissue Bank
Authors: Shiro Miura, Yuko Akazawa, Tomomi Kurashige, Kunihiro Tukasaki, Hisayoshi Kondo, Kenichi Yokota, Mariko Mine, Yasushi Miyazaki, Ichiro Sekine, Masahiro Nakashima
Journal: The Lancet (2015)
Cooperation of BRAFF595L and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling
Authors: M Kordes, M Röring, C Heining, S Braun, B Hutter, D Richter, C Geörg, C Scholl, S Gröschel, W Roth, A Rosenwald, E Geissinger, C von Kalle, D Jäger, B Brors, W Weichert, C Grüllich, H Glimm, T Brummer, S Fröhling
Journal: Leukemia (2015)
Object representations in the early memories of sexually abused borderline patients
Authors: J T Nigg, K R Silk, D Westen, N E Lohr, L J Gold, S Goodrich, S Ogata
Journal: American Journal of Psychiatry (1991)

This study analyzed psychological representations in 58 subjects in order to achieve a better understanding of the relation between adult borderline personality disorder and reported histories of childhood sexual and physical abuse.The subjects were 29 inpatients with borderline personality disorder diagnosed according to the Diagnostic Interview for Borderlines, 14 nonborderline inpatients with major depressive disorder according to the Research Diagnostic Criteria, and 15 normal comparison subjects recruited from the community and screened for the absence of psychopathology. Earliest memories were used as the source of mental representations in all subjects. The memories were reliably coded for malevolent affect tone, presence of deliberate injury, and effectiveness of helpers. Family histories of childhood sexual and physical abuse were obtained with the Familial Experiences Interview, a structured interview. Abuse histories for a subset of the subjects were corroborated by interviews with family members.A reported history of sexual abuse, but not a reported history of physical abuse, predicted the presence of extremely malevolent representations in these earliest memories as well as representations involving deliberate injury. These two kinds of representations also discriminated borderline patients who reported histories of sexual abuse from borderline patients who did not report sexual abuse. Mean affect tone (from malevolent to benevolent) did not, however, discriminate sexually abused or physically abused subjects.The results suggest that malevolent representations associated with the borderline diagnosis in previous research may be partially related to a history of childhood sexual abuse. Implications for the object relations theory of borderline personality disorder are noted.
SerpinB1 Promotes Pancreatic β Cell Proliferation
Authors: Abdelfattah El Ouaamari, Ercument Dirice, Nicholas Gedeon, Jiang Hu, Jian-Ying Zhou, Jun Shirakawa, Lifei Hou, Jessica Goodman, Christos Karampelias, Guifeng Qiang, Jeremie Boucher, Rachael Martinez, Marina A. Gritsenko, Dario F. De Jesus, Sevim Kahraman, Shweta Bhatt, Richard D. Smith, Hans-Dietmar Beer, Prapaporn Jungtrakoon, Yanping Gong, Allison B. Goldfine, Chong Wee Liew, Alessandro Doria, Olov Andersson, Wei-Jun Qian, Eileen Remold-O’Donnell, Rohit N. Kulkarni
Journal: Cell Metabolism (2015)
Abstract MP84: Use of Lifestyle Strategies Following Intervention and Impact on Longer-term Weight Loss Success
Authors: Margaret Lott, Laura Kinzel, Emma Barinas-Mitchell, Daniel G Winger, Li Wang, Molly B Conroy
Journal: Circulation (2014)

Background: Behavioral weight loss interventions are successful in producing weight loss; however, weight regain following cessation of intervention is common. Little is known about use of lifestyle strategies following interventions, differences in use by sex, and how use of strategies relates to longer-term weight trajectories. Methods: This analysis includes participants in the Slow the Adverse Vascular Effects of excess weight (SAVE) study with 24 month follow-up data. SAVE included 349 men and women aged 20-45 years with body mass index 25-39.9kg/m 2 . The SAVE weight loss intervention lasted for 18 months, with sessions decreasing in frequency over time. At 24 months, participants completed a survey about lifestyle strategies used in the past six months, including self-monitoring, group support, behavioral skills, and professional support. Chi-square and Fischer exact tests were used to compare frequency of strategies by sex. T tests were used to compare percent change in weight between baseline and 24-month by use of strategies vs. no use. Results: 214 participants completed 24 month visit (61% of baseline cohort). 74% were female and 86% were white, which did not differ from the baseline cohort. Overall, 65% used self-monitoring, 67% used group support, 94% used behavioral skills, and 27% used professional support within past 6 months. Recording physical activity (52%) and calories (43%) were the most common self-monitoring strategies. Self-weighing (83%), cue management (71%), and portion management (74%) were commonly used behavioral skills. Women were more likely than men to use group support (72% vs. 54%; p = .01). Women were also more likely to use the behavioral skills of rewarding success (32% vs. 9%; p = .001), portion management (78% vs. 64%; p = .046), and cue management (77% vs. 52%; p = .000). Women more frequently reported receiving professional support of diet counseling (48% vs. 15%; p = 0.04) or physical activity counseling (59% vs. 23%; p =0.02) from their PCP than men. Participants who used behavioral strategies had a significantly greater percent change in body weight at 24 months than those who did not (-3.9% vs. -0.7%; p =0.02). No significant differences were found in percent change in body weight at 24 months between participants who used self-monitoring, group support and professional support and those who did not. Conclusions: Participants who completed a weight loss intervention report using a variety of lifestyle strategies after cessation of intervention. Women reported more frequent use of lifestyle strategies than men. Behavioral strategies may be particularly important in longer-term weight loss. Attention should be paid to developing strategies to ensure longer-term weight loss after interventions.
Donor colonic CD103+ dendritic cells determine the severity of acute graft-versus-host disease
Authors: Motoko Koyama, Melody Cheong, Kate A. Markey, Kate H. Gartlan, Rachel D. Kuns, Kelly R. Locke, Katie E. Lineburg, Bianca E. Teal, Lucie Leveque-El mouttie, Mark D. Bunting, Slavica Vuckovic, Ping Zhang, Michele W.L. Teng, Antiopi Varelias, Siok-Keen Tey, Leesa F. Wockner, Christian R. Engwerda, Mark J. Smyth, Gabrielle T. Belz, Shaun R. McColl, Kelli P.A. MacDonald, Geoffrey R. Hill
Journal: The Journal of Experimental Medicine (2015)

The primacy of the gastrointestinal (GI) tract in dictating the outcome of graft-versus-host disease (GVHD) is broadly accepted; however, the mechanisms controlling this effect are poorly understood. Here, we demonstrate that GVHD markedly enhances alloantigen presentation within the mesenteric lymph nodes (mLNs), mediated by donor CD103+CD11b− dendritic cells (DCs) that migrate from the colon under the influence of CCR7. Expansion and differentiation of donor T cells specifically within the mLNs is driven by profound levels of alloantigen, IL-12, and IL-6 promoted by Toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signals. Critically, alloantigen presentation in the mLNs imprints gut-homing integrin signatures on donor T cells, leading to their emigration into the GI tract where they mediate fulminant disease. These data identify a critical, anatomically distinct, donor DC subset that amplifies GVHD. We thus highlight multiple therapeutic targets and the ability of GVHD, once initiated by recipient antigen-presenting cells, to generate a profound, localized, and lethal feed-forward cascade of donor DC–mediated indirect alloantigen presentation and cytokine secretion within the GI tract.
Abstract 50: The Association Between Carbon Dioxide, Cerebral Oxygenation and Survival in Post--Cardiac Arrest Patients
Authors: Koen Ameloot, Cathy De Deyne, Ingrid Meex, Cornelia Genbrugge, David Verhaert, Wilfried Mullens, Frank Jans, Mathias Dupont, Jo Dens
Journal: Circulation (2014)

Purpose:  the relationship between arterial carbon dioxide (CO2), cerebral saturation (SctO2) and patient survival has been poorly investigated in post-cardiac arrest patients. Current guidelines recommend to target CO2 levels between 40-45 mmHg although some authors recommend higher CO2 levels based on the hypothesis that hypercapnia may lead to increased cerebral perfusion. Therefore the aims of the present study were to explore the relationships between CO2, SctO2 and survival.   Methods:  Prospective observational study in 82 post-cardiac arrest patients treated with therapeutic hypothermia. Blood gasses were obtained with a 1 hour interval during the first 24 hours after admission. Cerebral saturation was monitored every 2 seconds with near infrared spectroscopy (NIRS)   Results:  The mean CO2 was 40±5mmHg and the mean SctO2 65±4%. Thirty-nine patients died and 43 survived (43/82 patients, 52%) until ICU discharge. The mean CO2 range during the first 24 hours after admission associated with maximal survival was 38-42mmHg (OR 2.84, 95% CI [1.15; 7.05], p=0.02). Subsequently, 2100 paired CO2/SctO2 measurements were analyzed. Based on our previous observation that the presumed ideal SctO2 is around 67%, the CO2/SctO2 scatterplot can be divided in 3 sections: (1) Hypocapnic cerebral desaturation: we found a strong linear relationship between CO2 and average SctO2 when CO2 was between 28-39mmHg (SctO2=0.50 x CO2 + 47, R2 0.76). (2) Normocapnic plateau phase: CO2’s between 40-45mmHg resulted in average SctO2’s between 66.5 and 67.5%. (3) Hypercapnic cerebral hypersaturation: we found a linear relationship between CO2 and average SctO2 when CO2 was between 46-62mmHg (SctO2=0.40 x CO2 + 47, R2 0.39). The predicted optimal CO2 (40-45mmHg) based on this physiological model corresponding with a SctO2 of 67% matched with the optimal CO2 (38-42mmHg) associated with maximal survival.   Conclusion:  Based on the relationship between CO2 and SctO2 and extensive survival analysis, the target CO2 in post-cardiac arrest patients seems to be 40mmHg. Since all patients received fully controlled mechanical ventilation, it is likely that there is causal relationship between iatrogenic hyperventilation/hypocapnia, cerebral desaturation and increased mortality.
Patterns of bronchodilator reversibility of FEV1 in asthma and COPD patients
Authors: Tushar Sahasrabudhe, Madhur Joshi, Vikas Oswal
Journal: European Respiratory Journal (2012)

SAMA (Short Acting Muscarinic Antagonist) has been said to be superior to SABA (Short Acting Beta Agonist) in COPD whereas SABA is preferred bronchodilator in asthma patients. In practice however we observe that the response is variable for individual patient. Therefore we evaluated improvement in FEV1 in 27 persistent asthmatics and 27 COPD patients in response to inhaled SABA (Salbutamol) and SAMA (Ipratropium) on separate days. These patients were in remission with no exacerbation or change of regular treatment in last 4 weeks. The washout period of their regular treatments was adhered to, before performing their spirometries. SABA produced mean increase of 16.66% and 401 ml in FEV1 of asthmatics vs. -1.44% and -15 ml change in FEV1 of COPD patients. SAMA produced 4.07% and 161 ml increase in FEV1 in asthmatics vs. 8.59% and 166 ml in COPD patients. The similar increase in FEV1 in ml in response to SAMA was more significant in FEV1% due to lower baseline FEV1 in COPD patients. An interesting fact observed was that with the increasing duration of Asthma and COPD, the reversibility with SAMA sequentially increased. With a cut off of more than 8 years of duration of disease, the average improvement in FEV1 in response to SAMA was 453ml (vs. 77 ml in less than 8 year duration) in asthma and 222 ml in COPD, whereas there was no significant change in response to SABA in both groups. There was no correlation with patient9s age or baseline FEV1 value. We conclude that inhaled muscarinic antagonists can be a beneficial adjunct to beta agonists in persistent asthmatics with longer duration of asthma.
Abstract P358: Assessing Global Dietary Habits: A Comparison of National Estimates from the Food and Agricultural Organization and the Global Dietary Database
Authors: Liana C Del Gobbo, Shahab Khatibzadeh, Renata Micha, Dariush Mozaffarian
Journal: Circulation (2014)

Background: Accurate data on dietary habits are crucial for understanding impacts on disease and informing policy priorities. National food availability estimates from the UN Food &amp; Agricultural Organization (FAO) have been widely used as the only global data available, but with uncertain validity. Objective: To investigate the validity of FAO data compared to nationally representative data on individual-based dietary intakes from the Global Dietary Database (GDD). Methods: We compared 30 y (1980-2010) of FAO food supply data, comprising 101 food items/y, matched to corresponding GDD survey data for113 countries across major food groups, including fruits &amp; fruit juices, vegetables, beans &amp; legumes, nuts &amp; seeds, whole grains, red &amp; processed meats, fish &amp; seafood, milk, and total energy. Absolute and percent differences in FAO-GDD country-year pairs were compared using t-tests. Statistical significance of heterogeneity was tested using likelihood ratio tests comparing nested models with and without interaction terms. Correction equations were developed and validated using randomly split datasets, using multivariate regression for FAO estimates as predictors of GDD results. Results: FAO estimates substantially overestimated individual-based dietary intakes for all food groups except beans &amp; legumes ( p &lt;0.0001) and nuts &amp; seeds ( p &lt;0.05). Modest heterogeneity in estimation was evident by age (Figure),sex, diet assessment method, and survey representativeness; substantial heterogeneity was observed by world region for all food groups ( p &lt;0.01). Results for split-data correction equations to be presented. Conclusion: For most food groups, FAO estimates were substantially different than individual-based national surveys, with significant heterogeneity according to several factors. Future national and global dietary analyses should rely on individual-based national survey data or multivariable-corrected FAO data for accurate assessment of undernutrition, disease burdens, and relevant policy.
Cockroach allergen exposure and risk of asthma
Authors: D. C. Do, Y. Zhao, P. Gao
Journal: Allergy (2015)

Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins have provided a basis for studying the mechanisms regarding cockroach allergen-induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen-presenting cell (APC) function in T-cell polarization, and cytokine production. Environmental pollutants, which often coexist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergen-induced innate immune responses, and the genetic basis for cockroach sensitization.
Comment on Rudland et al. Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c. Diabetes Care 2016;39:50–52
Authors: Amit Bhargava, Samreen Siddiqui, Swati Waghdhare, Sujeet Jha
Journal: Diabetes Care (2015)

We have read the analysis by Rudland et al. (1) with interest. Aside from demonstrating how the use of the new pregnancy-specific screening criteria (NSC) can provide a cost-effective approach to monogenic diabetes (maturity-onset diabetes of the young [MODY]) testing, the article highlights the crucial fact that the knowledge of a patient’s glucokinase [GCK]-MODY status may protect the fetus from harm from intensive glycemic control. We also greatly appreciate the fact that this study was carried out in a multiethnic cohort.

One point that we would like to highlight is that Southeast Asian women and Indian women are reported to have a …