tbuckley/cabot-search huggingface dataset:
The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors
Authors: Jeffrey S. Wieskopf, Jayanti Mathur, Walrati Limapichat, Michael R. Post, Mona Al-Qazzaz, Robert E. Sorge, Loren J. Martin, Dmitri V. Zaykin, Shad B. Smith, Kelen Freitas, Jean-Sebastien Austin, Feng Dai, Jie Zhang, Jaclyn Marcovitz, Alexander H. Tuttle, Peter M. Slepian, Sarah Clarke, Ryan M. Drenan, Jeff Janes, Shakir Al Sharari, Samantha K. Segall, Eske K. Aasvang, Weike Lai, Reinhard Bittner, Christopher I. Richards, Gary D. Slade, Henrik Kehlet, John Walker, Uwe Maskos, Jean-Pierre Changeux, Marshall Devor, William Maixner, Luda Diatchenko, Inna Belfer, Dennis A. Dougherty, Andrew I. Su, Sarah C. R. Lummis, M. Imad Damaj, Henry A. Lester, Ardem Patapoutian, Jeffrey S. Mogil
Journal: Science Translational Medicine (2015)

Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain.
Ventilator-associated pneumonia (VAP) - Early and late-onset differences
Authors: Margarida Dias, Paulo Marçal, Piedade Amaro
Journal: European Respiratory Journal (2013)

Background: VAP guidelines recommend choosing empirical antibiotic therapy based on time of diagnosis, presence of multidrug-resistant risk factors (MDR-RF) and local microbiologic data.

Objectives: To compare pathogens, length of intensive-care unit (ICU) stay and mortality in early-onset, early onset with MDR-RF and late-onset VAP.

Methods: Retrospective study of patients hospitalized in an ICU from 1/8/2001 to 31/12/2011 with VAP diagnosis and identified pathogen in lower airways. Three groups were defined: early-onset (< 5 days of intubation), early-onset and presence of MDR-RF and late-onset VAP (≥ 5 days of intubation). Potential MDR pathogens (methicillin-resistant S. aureus , P. aeruginosa , Acinectobacter sp . and extended spectrum beta-lactamases pathogens) and endpoints were compared between groups.

Results: We included 154 patients; 125 had late-onset VAP and 17 had early-onset with MDR-RF. Potential MDR pathogens were identified in 42% of early-onset VAP, in 59% of early-onset with MDR-RF and in 71% of late-onset VAP (p≥0.05).

Mortality for early-onset, early-onset with MDR-RF and late-onset VAP was 17%, 24% and 31% respectively (p≥0.05).

Mean length of ICU stay after VAP diagnosis of those who didn’t die in ICU (n=109) was higher in patients with late-onset VAP compared to early-onset without MDR-RF (20 vs 13 days, p=0.016).

Conclusion: Late-onset VAP was associated to a higher mortality (p≥0.05) and to a longer ICU stay.

The percentage of potential MDR pathogens was not significantly different between groups. There were few reports of early-onset VAP but high prevalence of these bacteria in this group may suggest the use of broad spectrum therapy in this ICU, until microbiologic results are ready.
A Brief Review of Computational Gene Prediction Methods
Authors: Zhuo Wang, Yazhu Chen, Yixue Li
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract With the development of genome sequencing for many organisms, more and more raw sequences need to be annotated. Gene prediction by computational methods for finding the location of protein coding regions is one of the essential issues in bioinformatics. Two classes of methods are generally adopted: similarity based searches and ab initio prediction. Here, we review the development of gene prediction methods, summarize the measures for evaluating predictor quality, highlight open problems in this area, and discuss future research directions.
Offspring of Patients Treated for Cancer in Childhood<xref ref-type="fn" rid="FN1">2</xref>
Authors: F P Li, W Fine, N Jaffe, G E Holmes, F F Holmes
Journal: JNCI Journal of the National Cancer Institute (1979)

Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalies or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments.
Distinct clinical and pathological phenotypes in IPF
Authors: Elisabetta Balestro, Fiorella Calabrese, Federico Rea, Emanuela Rossi, Francesca Lunardi, Marco Schiavon, Erica Bazzan, Monica Loy, Giuseppe Marulli, Nazarena Nannini, Graziella Turato, Simonetta Baraldo, Manuel Cosio, Marina Saetta
Journal: European Respiratory Journal (2013)

The clinical and functional course of IPF might deteriorate rapidly, rapid decliners (R) or slowly, slow decliners (S). Acute exacerbations (AE) are a feature of IPF. Lung pathology is considered to be similar in R and S; diffuse alveolar damage (DAD) is considered a common finding in AE.  The aim of the study was a) determine the frequency of S and R phenotypes and incidence of AE in a IPF population followed before transplant, and b) correlate the clinical course with the quantitative lung pathology in the explanted lungs.  59 IPF patients referred for lung transplant were followed for 37 (12-156) months. A 10% FVC fall/year cutoff was used to define the R (>10%) and S (  63% of patients were S and 37% were R. 74% of R and 73% of S were smokers. During the follow-up 23% of patients developed AE. The extension of lung abnormalities differed in the 3 groups; S had a significantly higher proportion of normal lung than R and AE (19 vs 9 vs 5% p  R and S decliners are different not only clinically but also pathologically and fulfill the definition of phenotypes. The degree of inflammation seen in R is the key finding separating the phenotypes. Smoking does not singly predispose for the R phenotype neither to the type and degree of lung inflammation.
Metabolic Effects of Exercise Training Among Fitness-Nonresponsive Patients With Type 2 Diabetes: The HART-D Study
Authors: Ambarish Pandey, Damon L. Swift, Darren K. McGuire, Colby R. Ayers, Ian J. Neeland, Steven N. Blair, Neil Johannsen, Conrad P. Earnest, Jarett D. Berry, Timothy S. Church
Journal: Diabetes Care (2015)

OBJECTIVE To evaluate the impact of exercise training (ET) on metabolic parameters among participants with type 2 diabetes mellitus (T2DM) who do not improve their cardiorespiratory fitness (CRF) with training. RESEARCH DESIGN AND METHODS We studied participants with T2DM participating in the Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes (HART-D) trial who were randomized to a control group or one of three supervised ET groups for 9 months. Fitness response to ET was defined as a change in measured peak absolute oxygen uptake (ΔVO2peak, in liters per minute) from baseline to follow-up. ET participants were classified based on ΔVO2peak into fitness responders (ΔVO2peak ≥5%) and nonresponders (ΔVO2peak &amp;lt;5%), and changes in metabolic profiles were compared across control, fitness responder, and fitness nonresponder groups. RESULTS A total of 202 participants (mean age 57.1 ± 7.9 years, 63% women) were included. Among the exercise groups (n = 161), there was substantial heterogeneity in ΔVO2peak; 57% had some improvement in CRF (ΔVO2peak &amp;gt;0), with only 36.6% having a ≥5% increase in VO2peak. Both fitness responders and nonresponders (respectively) had significant improvements in hemoglobin A1c and measures of adiposity (ΔHbA1c: −0.26% [95% CI −0.5 to −0.01] and −0.26% [−0.45 to −0.08]; Δwaist circumference: −2.6 cm [−3.7 to −1.5] and −1.8 cm [−2.6 to −1.0]; Δbody fat: −1.07% [−1.5 to −0.62] and −0.75% [−1.09 to −0.41]). No significant differences were observed in the degree of change of these metabolic parameters between fitness responders and nonresponders. Control group participants had no significant changes in any of these metabolic parameters. CONCLUSIONS ET is associated with significant improvements in metabolic parameters irrespective of improvement in cardiorespiratory fitness.
Abstract 86: CPR Parameters as Predictors of Return of Spontaneous Circulation Following Inpatient Cardiac Arrest
Authors: Rebecca E Sell, Ruchika D Husa, Morgan C Ludington, Daniel P Davis
Journal: Circulation (2011)

Background: The quality of cardiopulmonary resuscitation (CPR) parameters, including chest compression fraction (CCF) and compression depth, appear to be associated with return of spontaneous circulation (ROSC) in out-of-hospital cardiopulmonary arrest (CPA). In addition, end tidal carbon dioxide (EtCO2) may be useful as a marker for ROSC during low flow states such as CPA. Objective: To explore the relationship between CCF, compression depth, and EtCO2 for inpatient CPA. Methods: This study was conducted in two urban university hospitals. Defibrillator data are exported for analysis following all CPA events. Inpatient medical records were reviewed to determine baseline characteristics and outcomes. CPR data were analyzed in 1-min intervals over the entire CPA resuscitation. The pattern of CCF, compression depth, and EtCO2 were explored in ventricular fibrillation (VF) and non-VF patients and in those with and without ROSC. Results: A total of 23 CPAs were analyzed between 5/31/09 and 4/23/11. There were 14 with ROSC and 9 without ROSC. The majority of arrests were non-VF (87%). The mean values were calculated for code duration (13 min), CCF (92%), compression depth (2.8 inches), and EtCO2 (20.3 mm Hg). Code duration was shorter (8.8 vs. 19.8 min) and CCF values higher (93.1% vs. 89.5%) in patients with ROSC. EtCO2 values were higher in VF patients with ROSC (17 vs. 11 mmHg) but not for all rhythms. In addition, terminal EtCO2 values were higher when compared to mean EtCO2 values in ROSC patients than for non-ROSC patients. Conclusion: For this small sample of inpatient cardiac arrests, patients with ROSC had shorter code durations, higher CCF values, deeper compressions, and higher terminal EtCO2 values. These data support the importance of optimal CPR in the inpatient setting.
The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis
Authors: Hok-Hay S Oei, Rozemarijn Vliegenthart, A.Elisabeth Hak, Antonio Iglesias del Sol, Albert Hofman, Matthijs Oudkerk, Jacqueline C.M Witteman
Journal: Journal of the American College of Cardiology (2002)
Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial
Authors: Rakshit Panwar, Miranda Hardie, Rinaldo Bellomo, Loïc Barrot, Glenn M. Eastwood, Paul J. Young, Gilles Capellier, Peter W. J. Harrigan, Michael Bailey
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients.To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV).At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51).The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO2 (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO2 (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FiO2 (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO2 less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO2 greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO2/FiO2 less than 300.Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).
Detection of Marek's Disease Antigen in Feather Follicle Epithelium of Chickens Vaccinated Against Marek's Disease<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref>
Authors: C. S. Eidson, O. J. Fletcher, S. H. Kleven, D. P. Anderson
Journal: JNCI Journal of the National Cancer Institute (1971)

Marek's disease (MD) is a lymphoproliferative disease of chickens caused by a group B herpesvirus. A turkey herpesvirus (HVT) vaccine, injected intra-abdominally or subcutaneously into 1-day-old chicks, protects against development of MD. The vaccine protected birds challenged with Marek's disease virus (MDV) either by contact exposure or parenteral inoculation. Although HVT vaccine prevented tumor development and clinical disease, it did not prevent infection or replication of virulent MDV. MDV was isolated from sonically treated skin samples from vaccinated birds challenged with MDV. Vaccinated birds had both HVT and MDV and antibodies against each. The MD, but not the HVT, antigen could be detected by the direct fluorescent antibody test in the feather follicle epithelium of birds vaccinated at 1 day of age with either the FC126 or WHG-HVT isolates and subsequently challenged with MDV when 3 weeks old. This indicated that vaccinated birds shed virulent MDV in the feather follicle epithelium like unvaccinated, infected birds. One-day-old chicks, given injections of plasma from vaccinated, infected donor birds, containing both HVT and MDV, developed MD lesions. Also, controls reared in direct contact with vaccinated birds developed MD when challenged with MDV.
Risk of intracranial haemorrhage linked to co-treatment with antidepressants and NSAIDs
Authors: Stewart W Mercer, Rupert A Payne, Barbara I Nicholl, Jill Morrison
Journal: BMJ (2015)

Important implications for primary care doctors and patients with multimorbidity

The linked paper by Shin and colleagues (doi:10.1136/bmj.h3517) offers important new evidence about the relation between antidepressant drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and the incidence of intracranial haemorrhage.1 Although NSAIDs and antidepressants are both associated with an increased risk of gastrointestinal bleeding, previous evidence has not shown clear links between intracranial haemorrhage and either type of drug when used alone. The new study, however, set out to define the risk of such bleeds when the two classes of drugs are combined, and the results give some cause for concern. In a retrospective population cohort study of more than four million people in Korea, the authors found that the combination of antidepressants and NSAIDs was associated with a substantially increased risk of intracranial haemorrhage, compared with antidepressant treatment alone.

Antidepressants are widely prescribed globally, and their use is increasing.2 3 4 In England, almost 40 million antidepressant prescriptions were issued in 2012, compared with just under 15 million in 1998.4 NSAIDs are also widely used, often without prescription and in non-pharmacy settings. Oral analgesics accounted for 739 million items in …
Iron Trafficking and Distribution in Transfusional Overload: Insights From Comparing Diamond Blackfan Anemia with Sickle Cell Disease and Thalassemia
Authors: John B. Porter, Patrick B Walter, Lynne D Neumayr, Patricia Evans, Marcela G Weyhmiller, Paul Harmatz, John C Wood, Jeffery L. Miller, Guenter Weiss, Qing Yuan, Zhiyue J Wang, Regine Grosse, Bjoern P Schoennagel, Joerg Meerpohl, Roland Fischer, Elliott Vichinsky
Journal: Blood (2012)
Declining altruism in medicine
Authors: K. Fleming
Journal: BMJ (2002)

Editor—In his editorial Jones described the decline of altruism in medicine.1 As Claire Luce Booth—a congresswoman, ambassador, playwright, socialite, and wife of American magazine magnate Henry R Luce—noted, “No good deed goes unpunished.”2 Business authors have described that individuals in the employ of service industries (such as medicine) have two levels of service to offer. The most basic level of service is the performance of specified duties only, just enough to avoid being fired and nothing more. All the rest is “volunteer” work: going the extra mile for patients, doing more than you have to do, including doing some of it for free, are all efforts in excess of that which can be compelled by a job description. Love of one's work and patients begets such volunteering. Such is the way of altruism.

When volunteerism declines in any service industry, the blame falls on the work environment. As doctors learn that there is little or no emotional or financial reward for voluntary addenda to patient care and that such behaviours may actually be punished, the natural tendency is to work to the rule. Only that which is required gets performed. Punishment of physicians is indeed effective, but the results are not those intended by administrators, lawyers, and regulators.
Clearance of Blood Radioiodide by Transplantable Tumors of the Thyroid Gland in the Unanesthetized Rat
Authors: Seymour H. Wollman, Franklin E. Reed
Journal: JNCI Journal of the National Cancer Institute (1963)

Measurements were made of the clearance of blood radioiodide by transplantable tumors of the thyroid gland in the Fischer rat. In two lines the clearance was proportional to tumor mass. Clearance by the thyroid gland was relatively unaffected by tumors of line 1-2. Clearance by the thyroid gland was depressed to that in hypophy-sectomized rats by tumors of another line (1-1C) when the total tumor clearance was greater than twice the thyroid clearance. The clearance was of the order of 0.5 ml blood per g tumor per minute for tumors of some lines and approximately 0.08 ml blood per g tumor per minute for others. This indicates that the volume flow of blood in some tumors approximates that of the more actively perfused organs.
Building Evidence for Global Surgery One Experience at a Time
Authors: Haile T. Debas
Journal: JAMA Surgery (2015)

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Lung adenocarcinoma with type II pneumocyte characteristics
Authors: S Tsutahara, N Shijubo, M Hirasawa, Y Honda, M Satoh, Y Kuroki, T Akino
Journal: European Respiratory Journal (1993)

We report a case of primary lung adenocarcinoma with type II pneumocyte characteristics. Electron microscopic examination demonstrated that the tumour cells had well-developed microvilli and cytoplasmic lamellar inclusion bodies. These ultrastructural features are similar to those seen in type II pneumocytes of normal lung tissue. Western blot analysis, using monoclonal antibody against human surfactant protein A (SP-A), clearly demonstrated that the tumour cells expressed human SP-A, which is a major pulmonary surfactant protein produced by type II pneumocytes. These observations suggest that the tumour was derived from a type II pneumocyte.