Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-Pneumococcal Capsular Polysaccharide Antibody Response and CD5 B Lymphocyte Subsets

ABSTRACT The role of CD19+ CD5+ and CD19+ CD5− B cell subpopulations in the antibody response to pneumococcal capsular polysaccharides (caps-PSs) is controversial. In the present study, we evaluated the role of human CD19+ CD5+ and CD19+ CD5− cell populations in the serotype-specific antibody response to caps-PS. After vaccination of 5 healthy human adults with Pneumovax (23-valent pneumococcal polysaccharide vaccine [PPV23]), IgG anti-caps-PS serotype 4 antibody-producing cells resided mainly in the CD19+ CD5− B cell subset, as assessed by enzyme-linked immunosorbent spot (ELISpot) analysis. Moreover, in a humanized SCID mouse model, CD19+ CD5− B cells were more effective than CD19+ CD5+ cells in producing IgG anti-cap-PS antibodies. Finally, an association was found between the level of IgG anti-caps-PS antibodies and the number of CD19+ CD5− B cells in 33 humans vaccinated with PPV23. Taken together, our data suggest that CD5 defines a functionally distinct population of B cells in humans in the anti-caps-PS immune response.
Visual and flight performance recovery after PRK or LASIK in helicopter pilots.

INTRODUCTION Refractive surgery, specifically photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK), is becoming more accepted in the military environment. Determination of the impact on visual performance in the more demanding aviation environment was the impetus for this study. METHODS A prospective evaluation of 20 Black Hawk pilots pre-surgically and at 1 wk, 1 mo, and 6 mo postsurgery was conducted to assess both PRK and LASIK visual and flight performance outcomes on the return of aviators to duty. RESULTS Of 20 pilots, 19 returned to flight status at 1 mo after surgery; 1 PRK subject was delayed due to corneal haze and subjective visual symptoms. Improvements were seen under simulator night and night vision goggle flight after LASIK; no significant changes in flight performance were measured in the aircraft. Results indicated a significantly faster recovery of all visual performance outcomes 1 wk after LASIK vs. PRK, with no difference between procedures at 1 and 6 mo. Low contrast acuity and contrast sensitivity only weakly correlated to flight performance in the early post-operative period. DISCUSSION Overall flight performance assessed in this study after PRK and LASIK was stable or improved from baseline, indicating a resilience of performance despite measured decrements in visual performance, especially in PRK. More visually demanding flight tasks may be impacted by subtle changes in visual performance. Contrast tests are more sensitive to the effects of refractive surgical intervention and may prove to be a better indicator of visual recovery for return to flight status.
mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option.

BACKGROUND The mammalian target of rapamycin (mTOR) pathway inhibition has emerged as one of the main directions for the development of new targeted agents in renal cell carcinoma (RCC). A prominent member in its class of medications, temsirolimus has already been shown to improve overall survival in advanced kidney cancer, when compared with the previous standard, IFN-alpha. OBJECTIVE The aim of this study was to review the most relevant preclinical and clinical data on the mTOR inhibitors, both in clinical use or in current development. METHODS The authors give a comprehensive review of the existing English literature on the role of the mTOR pathway in renal tumorigenesis, as well as a detailed safety and efficacy analysis of older and newer rapamycin analogs. RESULTS/CONCLUSIONS Rapamycin derivatives temsirolimus and everolimus have significant clinical activity in patients with advanced-stage RCC. Both parenteral and oral formulations of mTOR inhibitors have shown clinical efficacy and are currently being developed. Combinations of mTOR inhibitors with VEGF/VEGFR-blocking agents are also being studied, in an attempt to further enhance the antineoplastic effect.
A novel option for prandial insulin therapy: inhaled insulin

ABSTRACT Many adults with type 2 diabetes (T2D) do not achieve or maintain glycemic targets on oral antidiabetes drugs (OADs) alone and require insulin therapy. Although initiating basal insulin is common when treatment needs to be intensified, individualization of therapy (in line with current guidelines) may lead more health care professionals (HCPs) to add rapid-acting insulin (RAI) to OAD regimens for treatment of postprandial hyperglycemia to achieve glycated hemoglobin (A1C) targets. HCPs and patients are concerned about the burden associated with injections. Inhaled Technosphere® insulin (inhaled TI) – as an alternative to injectable bolus doses of prandial insulin – may increase patient and HCP willingness to intensify therapy and improve compliance with more complex regimens. Clinical studies have shown that inhaled TI is effective and well tolerated as a prandial insulin, and has the potential to improve treatment satisfaction and quality of life in adults with T2D. The favorable pharmacokinetic profile of inhaled TI (i.e., a very rapid onset of action and a short duration of anti-hyperglycemic effect) may reduce the risk of insulin stacking (overlapping effects of RAI injections taken < 4 hours apart) and postprandial hypoglycemia. In this review, we present inhaled TI as an alternative to OADs or injected insulin as adjunctive therapy, for consideration by HCPs striving to achieve glycemic targets for their patients.
Incidence and predictors of critical events during urgent air–medical transport

Background: Little is known about the risks of urgent air–medical transport used in regionalized health care systems. We sought to determine the incidence of intransit critical events and identify factors associated with these events. Methods: We conducted a population-based, retrospective cohort study using clinical and administrative data. We included all adults undergoing urgent air–medical transport in the Canadian province of Ontario between Jan. 1, 2004, and May 31, 2006. The primary outcome was in-transit critical events, which we defined as death, major resuscitative procedure, hemodynamic deterioration, or inadvertent extubation or respiratory arrest. Results: We identified 19 228 patients who underwent air–medical transport during the study period. In-transit critical events were observed in 5.1% of all transports, for a rate of 1 event per 12.6 hours of transit time. Events consisted primarily of new hypotension or airway management procedures. Independent predictors of critical events included female sex (adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1–1.5), assisted ventilation before transport (adjusted OR 3.0, 95% CI 2.3–3.7), hemodynamic instability before transport (adjusted OR 3.2, 95% CI 2.5–4.1), transport in a fixed-wing aircraft (adjusted OR 1.5, 95% CI 1.2–1.8), increased duration of transport (adjusted OR 1.02 per 10-minute increment, 95% CI 1.01–1.03), on-scene calls (adjusted OR 1.7, 95% CI 1.4–2.1) and type of crew (adjusted OR 0.6 for advanced care paramedics v. critical care paramedics, 95% CI 0.5–0.7). Interpretation: Critical events occurred in about 1 in every 20 air–medical transports and were associated with multiple risk factors at the patient, transport and system levels. These findings have implications for the refinement of training of paramedic transport crews and processes for triage and transport.
Identification of a VxP Targeting Signal in the Flagellar Na+/K+‐ATPase

Na+/K+‐ATPase (NKA) participates in setting electrochemical gradients, cardiotonic steroid signaling and cellular adhesion. Distinct isoforms of NKA are found in different tissues and subcellular localization patterns. For example, NKA α1 is widely expressed, NKA α3 is enriched in neurons and NKA α4 is a testes‐specific isoform found in sperm flagella. In some tissues, ankyrin, a key component of the membrane cytoskeleton, can regulate the trafficking of NKA. In the retina, NKA and ankyrin‐B are expressed in multiple cell types and immunostaining for each is striking in the synaptic layers. Labeling for NKA is also prominent along the inner segment plasma membrane (ISPM) of photoreceptors. NKA co‐immunoprecipitates with ankyrin‐B, but on a subcellular level colocalization of these two proteins varies dependent on the cell type. We used transgenic Xenopus laevis tadpoles to evaluate the subcellular trafficking of NKA in photoreceptors. GFP‐NKA α3 and α1 are localized to the ISPM, but α4 is localized to outer segments (OSs). We identified a VxP motif responsible for the OS targeting by using a series of chimeric and mutant NKA constructs. This motif is similar to previously identified ciliary targeting motifs. Given the structural similarities between OSs and flagella, our findings shed light on the subcellular targeting of this testes‐specific NKA isoform.
Sulfate supplementation of growing goats: effects on performance, acid-base balance, and nutrient digestibilities.

Castrated male goat kids (20 Alpine, 12 Angora) were individually fed isonitrogenous and isoenergetic diets containing 2.28% N and S (added as CaSO4) at either . 11 (basal), . 20, . 28, or . 38% of dietary DM. Sulfate supplementation during the 8-wk growth trial quadratically increased ADG (P < .05) and tended to increase quadratically the DMI (P < .07) of goats, with a peak value for the . 20% S diet. Even when analyzed using DMI as a covariate, ADG was quadratically increased (P < .05) by added S. Sulfate supplementation linearly increased (P < .001) S intake, fecal S output, and S retention. Sulfate supplementation tended to increase quadratically (P < .06) the blood plasma concentration of L-lactate. However, sulfate supplementation did not significantly affect (P > .10) plasma sulfate, plasma cystine, ruminal ammonia N concentrations, or purine N content of isolated ruminal bacteria. Sulfate supplementation quadratically increased (P < .05) fractional N retention. Urinary output of uric acid increased quadratically (P < .01) with S supplementation, presumably reflecting ruminal bacterial protein synthesis. Calculated by regression, the optimal dietary S content for maximum ADG was . 22% S (N:S = 10.4:1), for maximum DMI it was . 24% S (N:S = 9.5: 1), for maximum N retention it was . 23% (N:S = 9.9: 1), and for maximum absorbed N retained it was . 22% (N:S = 10.4:1). These results support the current estimate of the S requirement of goats for growth (N:S = 10:1).
At least one in seven cases of cancer is caused by smoking. Global estimates for 1985

Tobacco smoking is accepted as a major cause of cancers of the lung, larynx, oral cavity and pharynx, oesophagus, pancreas, kidney and bladder. The proportions of these cancers that are due to smoking were estimated for the year 1985 for 24 areas of the world. Fifteen percent—1. 1 million new cases per year—of all cancer cases are attributed to cigarette smoking, 25% in men and 4% in women. In developed countries, the tobacco burden is estimated at 16% of all annual incident cases. In developing countries, the corresponding figure is 10%. In total, 85% of the 676 000 cases of lung cancer in men are attributable to tobacco smoking. The highest attributable fractions (AF: 90–93%) are estimated in areas where the habit of cigarette smoking in men has been longest established: North America, Europe, Australia/New Zealand and the former USSR. Among the other 6 cancer sites considered in this analysis, those with the largest fractions of tobacco‐related cases are the larynx, mouth and pharynx (excluding nasopharynx) and oesophagus. In regions where males have smoked for several decades, 30 to 40% of all cancers in this sex are attributable to tobacco. Unless tobacco‐control efforts in developing countries are strengthened, the massive rise in cigarette consumption over the last few decades will produce a comparable rise in cancer in these countries within the next 20 to 30 years. © 1994 Wiley‐Liss, Inc.
Proximité et démarches participatives à l’Isle-aux-Grues et l’Isle-aux-Coudres (Québec)

Cet article traite du developpement de deux territoires insulaires du fleuve Saint -Laurent (Quebec) : l’Isle-aux-Grues et l’Isle-aux-Coudres. Nous y etudions la mise en œuvre de demarches participatives. Nous utilisons l’analyse des relations de proximite entre acteurs pour decrire le contexte social et spatial dans lequel ces demarches participatives s’inserent. Cette analyse met en relief les specificites insulaires. Ces specificites sont a la fois un atout (notamment par les logiques de proximites qui s’y manifestent) et une contrainte (degre eleve d’interconnaissance pesant sur les demarches, conflits d’usage, ouverture parfois difficile aux nouveaux arrivants) au developpement de ces milieux. Les demarches participatives etudiees ont favorise l’ouverture de nouveaux espaces de dialogue entre les acteurs. Pour cela, elles se sont appuyees sur les formes de proximites preexistantes (identite territoriale, liens professionnels) et en ont genere de nouvelles (mise en reseau, objectif commun). Cependant certaines relations de proximite, comme des clivages sociaux et sectoriels ou l’isolement, peuvent etre contraignantes et limiter la portee de ces demarches.
Prediction of Juvenile-Onset Myopia.

IMPORTANCE Myopia (nearsightedness) has its onset in childhood and affects about one-third of adults in the United States. Along with its high prevalence, myopia is expensive to correct and is associated with ocular diseases that include glaucoma and retinal detachment. OBJECTIVE To determine the best set of predictors for myopia onset in school-aged children. DESIGN, SETTING, AND PARTICIPANTS The Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study was an observational cohort study of ocular development and myopia onset conducted at 5 clinical sites from September 1, 1989, through May 22, 2010. Data were collected from 4512 ethnically diverse, nonmyopic school-aged children from grades 1 through 8 (baseline grades 1 through 6) (ages 6 through 13 years [baseline, 6 through 11 years]). MAIN OUTCOMES AND MEASURES We evaluated 13 candidate risk factors for their ability to predict the onset of myopia. Myopia onset was defined as -0.75 diopters or more of myopia in each principal meridian in the right eye as measured by cycloplegic autorefraction at any visit after baseline until grade 8 (age 13 years). We evaluated risk factors using odds ratios from discrete time survival analysis, the area under the curve, and cross validation. RESULTS A total of 414 children became myopic from grades 2 through 8 (ages 7 through 13 years). Of the 13 factors evaluated, 10 were associated with the risk for myopia onset (P < .05). Of these 10 factors, 8 retained their association in multivariate models: spherical equivalent refractive error at baseline, parental myopia, axial length, corneal power, crystalline lens power, ratio of accommodative convergence to accommodation (AC/A ratio), horizontal/vertical astigmatism magnitude, and visual activity. A less hyperopic/more myopic baseline refractive error was consistently associated with risk of myopia onset in multivariate models (odds ratios from 0.02 to 0.13, P < .001), while near work, time outdoors, and having myopic parents were not. Spherical equivalent refractive error was the single best predictive factor that performed as well as all 8 factors together, with an area under the curve (C statistic) ranging from 0.87 to 0.93 (95% CI, 0.79-0.99). CONCLUSIONS AND RELEVANCE Future myopia can be predicted in a nonmyopic child using a simple, single measure of refractive error. Future trials for prevention of myopia should target the child with low hyperopia as the child at risk.
What factors predict full or partial return to work among sickness absentees with spinal pain participating in rehabilitation?

Purpose. To identify the factors that predict full or partial return to work among long-term (≥90 days) sickness absentees due to spinal pain who begin a multidisciplinary rehabilitation programme. Method. In a prospective cohort study, 312 patients with neck, thoracic and/or lumbar pain, aged 20–64, participated in a 4-week multidisciplinary rehabilitation programme in Sweden. Questionnaire data at inclusion were used. Factors included in logistic regressions were as follows: age, gender, type of work, pain location, pain intensity (visual analogue scale), activity limitations [Disability Rating Index (DRI)], health-related quality of life (SF-36), pain-related fear of movement (Tampa Scale of Kinesiophobia), motivation (Self Motivation Inventory), sickness absence at baseline and number of sick-leave days during the previous 2 years. Outcome factor was increased versus not increased working time at follow-up 6 months later. Results. Most patients (68%) reported two or three pain locations. At baseline, 56% were full-time sickness absent and 23% at follow-up; 61% had increased their working time. Predictors for increased working time were age below 40 years, low activity limitation (DRI < 50), low SF-36 bodily pain (>30) and high SF-36 social functioning (>60). Number of sick-leave days during the previous 2 years (md 360; range 90–730) had no influence. Conclusions. Even patients with long previous sick leave can increase working time after a multidisciplinary rehabilitation programme, especially if they are younger, have lower levels of activity limitations and pain and better social functioning. To include information on part-time work is useful when evaluating work ability following rehabilitation programmes.
Deep Brain Stimulation for Parkinson’s Disease: Correlation between Intraoperative Subthalamic Nucleus Neurophysiology and Most Effective Contacts

Though intraoperative neurophysiology is essential to precisely define the definitive target, little is known regarding its predictive value in defining the most effective contact for chronic deep brain stimulation. In this retrospective study, we reviewed the correlation between intraoperative neurophysiology and contacts selected for chronic stimulation. Twenty consecutive patients implanted for subthalamic nucleus (STN) stimulation were reviewed. There was no significant correlation between the electrophysiologically defined STN and the most effective contact for chronic stimulation at 3 months or at 6 months. Furthermore, there was a discrepancy between the most effective contact for rigidity versus akinesia or tremor at 3 months. Interestingly, at 3 months, the same electrode contact was maximally efficient for rigidity, akinesia and tremor in only 13 of the 39 cases. This lack of correlation did not affect the global improvement.
Cultured endothelial cells display endogenous activation of the canonical Wnt signaling pathway and express multiple ligands, receptors, and secreted modulators of Wnt signaling

A growing body of evidence implicates Wnt signaling in the control of angiogenesis. To better understand the role of the Wnt/β‐catenin pathway in endothelial cells (EC), we examined endogenous signaling activity and signaling component expression in vascular cells. We observed stabilization of cytosolic β‐catenin and activation of a T‐cell factor (TCF) ‐luciferase promoter, hallmarks of canonical Wnt signaling activity, in cultured EC. This activity was increased in subconfluent EC, which are known to display characteristics of angiogenic EC, compared with confluent EC, which have a more differentiated phenotype. Endogenous TCF activity was inhibited by transfection with a secreted inhibitor of canonical Wnt signaling. A systematic analysis of Wnt, Fzd, SFRP, and Dkk gene expression in human EC (cultured and freshly isolated), smooth muscle cells (cultured), and aorta demonstrated that numerous Wnt signaling components are expressed by vascular cells. We conclude that Wnt signaling components are expressed and active in cultured EC. Developmental Dynamics 235:3110–3120, 2006. © 2006 Wiley‐Liss, Inc.
Strengthening Capacity to Limit Intrusion: Theorizing Family Health Promotion in the Aftermath of Woman Abuse

Children’s health is a key factor in women’s decisions to leave abusive partners, yet how these families promote their health after leaving is poorly understood. In this feminist grounded theory study, the authors conducted repeat interviews with 40 single-parent families that had left abusive partners/fathers and analyzed the data using constant comparative methods. Findings reveal the central problem faced by families is intrusion, unwanted interference in everyday life that stems from abuse and its fallout. Over time, families promote their health through the basic social process of strengthening capacity to limit intrusion via four subprocesses: providing, regenerating family, renewing self, and rebuilding security. Depending on the degree of intrusion, the focus strengthening capacity shifts between practical goals of surviving and more proactive efforts directed toward positioning for the future. This theory adds to our knowledge of the long-term consequences of IPV for families and provides direction for practice and policy.
Regulation of Carbohydrate Energy Metabolism in Drosophila melanogaster

Carbohydrate metabolism is essential for cellular energy balance as well as for the biosynthesis of new cellular building blocks. As animal nutrient intake displays temporal fluctuations and each cell type within the animal possesses specific metabolic needs, elaborate regulatory systems are needed to coordinate carbohydrate metabolism in time and space. Carbohydrate metabolism is regulated locally through gene regulatory networks and signaling pathways, which receive inputs from nutrient sensors as well as other pathways, such as developmental signals. Superimposed on cell-intrinsic control, hormonal signaling mediates intertissue information to maintain organismal homeostasis. Misregulation of carbohydrate metabolism is causative for many human diseases, such as diabetes and cancer. Recent work in Drosophila melanogaster has uncovered new regulators of carbohydrate metabolism and introduced novel physiological roles for previously known pathways. Moreover, genetically tractable Drosophila models to study carbohydrate metabolism-related human diseases have provided new insight into the mechanisms of pathogenesis. Due to the high degree of conservation of relevant regulatory pathways, as well as vast possibilities for the analysis of gene–nutrient interactions and tissue-specific gene function, Drosophila is emerging as an important model system for research on carbohydrate metabolism.
Delaying Corn Rootworm Resistance to Bt Corn

ABSTRACT Transgenic crops producing Bacillus thuringiensis (Bt) toxins for insect control have been successful, but their efficacy is reduced when pests evolve resistance. To delay pest resistance to Bt crops, the U.S. Environmental Protection Agency (EPA) has required refuges of host plants that do not produce Bt toxins to promote survival of susceptible pests. Such refuges are expected to be most effective if the Bt plants deliver a dose of toxin high enough to kill nearly all hybrid progeny produced by matings between resistant and susceptible pests. In 2003, the EPA first registered corn, Zea mays L. , producing a Bt toxin (Cry3Bb1) that kills western corn rootworm, Diabrotica virgifera virgifera LeConte, one of the most economically important crop pests in the United States. The EPA requires minimum refuges of 20% for Cry3Bb1 corn and 5% for corn producing two Bt toxins active against corn rootworms. We conclude that the current refuge requirements are not adequate, because Bt corn hybrids active against corn rootworms do not meet the high-dose standard, and western corn rootworm has rapidly evolved resistance to Cry3Bb1 corn in the laboratory, greenhouse, and field. Accordingly, we recommend increasing the minimum refuge for Bt corn targeting corn rootworms to 50% for plants producing one toxin active against these pests and to 20% for plants producing two toxins active against these pests. Increasing the minimum refuge percentage can help to delay pest resistance, encourage integrated pest management, and promote more sustainable crop protection.