Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary health care accessibility challenges in remote indigenous communities in Canada's North

Background Despite many improvements, health disparities between indigenous and non-indigenous populations in Canada's North persist. While a strong primary health care (PHC) system improves the health of a population, the majority of indigenous communities are very remote, and their access to PHC services is likely reduced. Understanding the challenges in accessing PHC services in these communities is necessary to improve the health of the population. Objective The objective of the study was to document and analyze the challenges in accessing PHC services by indigenous people in remote communities in Canada's Northwest Territories (NWT) from the perspectives of users and providers of PHC services. Methods Using explorative, qualitative methods, our study involved 14 semi-structured interviews with PHC service providers (SPs) and service users (SUs) in 5 communities across the NWT which varied according to population, remoteness, ethnic composition and health care resources. The interview guide was developed after key informant consultations. Results Both SPs and SUs understood the constraints in providing equitable access to PHC services in remote communities. The provision of emergency care was found to be particularly challenging, because of the lack of qualified staff in the community and the dependence on aeromedical evacuations. Wider dissemination of first aid skills among community members was seen to cover some gaps and also increase self-confidence. For non-emergency care, the need to travel outside the community was generally disliked. All recognized the need for more preventive services which were often postponed or delayed because of the overwhelming demand for acute care. As long as services were provided in a community, the satisfaction was high among SUs. SPs appreciated the orientation they received and the ability to build rapport with the community. Conclusions Northern SUs and SPs generally acknowledge the health consequences of living in remote communities. The generally high level of satisfaction attests to the overall effectiveness of PHC in the region despite geographical remoteness. Many improvements could be made in terms of upgrading the clinical skills of SPs and community members, improving staff retention, extending the frequency and duration of community visits and providing more attention to preventive services.
Esophageal Stricture Prevention after Endoscopic Submucosal Dissection

Advances in diagnostic modalities and improvement in surveillance programs for Barrett esophagus has resulted in an increase in the incidence of superficial esophageal cancers (SECs). SEC, due to their limited metastatic potential, are amenable to non-invasive treatment modalities. Endoscopic ultrasound, endoscopic mucosal resection, and endoscopic submucosal dissection (ESD) are some of the new modalities that gastroenterologists have used over the last decade to diagnose and treat SEC. However, esophageal stricture (ES) is a very common complication and a major cause of morbidity post-ESD. In the past few years, there has been a tremendous effort to reduce the incidence of ES among patients undergoing ESD. Steroids have shown the most consistent results over time with minimal complications although the preferred mode of delivery is debatable, with both systemic and local therapy having pros and cons for specific subgroups of patients. Newer modalities such as esophageal stents, autologous cell sheet transplantation, polyglycolic acid, and tranilast have shown promising results but the depth of experience with these methods is still limited. We have summarized case reports, prospective single center studies, and randomized controlled trials describing the various methods intended to reduce the incidence of ES after ESD. Indications, techniques, outcomes, limitations, and reported complications are discussed.
Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection

Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.
Thirty-Year Experience With ACL Reconstruction Using Patellar Tendon: A Critical Evaluation of Revision and Reoperation

Background: During the preoperative discussion prior to anterior cruciate ligament reconstruction (ACLR), patients are often interested in data regarding rates of revision reconstruction, reoperation, concomitant pathologic changes, and future contralateral ACL injury. Purpose: To analyze a single surgeon’s experience with primary and revision ACLR over a 30-year interval, focusing on incidence and risk factors for revision and reoperation. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent ACLR from 1986 to 2016 were identified from a prospectively maintained database. Covariates of interest included age, sex, time, and graft selection. Outcomes of interest included revision and reoperation rates. Results: A total of 2450 ACLRs (mean patient age, 29 years; 58% male) were reviewed. Among primary ACLRs performed (n = 2225), 68% entailed bone–patellar tendon–bone (BTB) autograft and 30% entailed BTB allograft. Patients undergoing ACLR with autograft and allograft had a mean age of 22 and 37 years, respectively. The rate of revision ACLR was 1.8% and 3.5% for primary and revision cases, respectively. An increased rate of revision was noted among females compared with males (2.6% vs 1.2%) and among allografts compared with autografts (2.7% vs 1.3%). Low-dose irradiation did not affect allograft revision rates. The nonrevision reoperation rate following primary ACLR was 12%. The nonrevision reoperation rate was lower among primary cases reconstructed with allograft than autograft (9% vs 13%). Seventeen percent of cases involved concomitant meniscal repair and, among these, 13% required revision meniscal surgery. The rate of contralateral ACLR was 5.3% Conclusion: This information is useful in the informed consent process, for perioperative decision making regarding graft choice, and for identifying patients who are at risk for injuring the uninvolved knee.
Mutation analysis in 46 British and Irish patients with Gaucher’s disease

DNA from 46 unrelated patients with Gaucher’s disease was analysed for 10 known mutations: 84GG(c84 G 85ins), N370S (c1226G), L444P (c1448C), R463C (c1504T), R496H (c1604A), IVS2+1, D409H (c1342C), RecNciI (c1448C-1498C), RecTL (c1342C-1498C), and c1263del (c1264-1318del). Fifty four mutations (90%) were identified in 30 patients with type I disease. These included a previously undescribed recombinant mutation RecA456P (c1448C-1484C). Thirteen (54%) of 24 type II alleles were identified, including one new point mutation N462K (c1503G) and one new 55bp deletion also incorporating the RecTL mutations c1263del+RecTL (c1264del-1498C). All four type III patients were homozygous for the L444P point mutation. Generally, patients with one copy of the N370S mutation had mild adult onset disease, regardless of the nature of their second mutation. Three exceptions had childhood onset disease and genotypes N370S/R463C, N370S/RecA456P, and N370S/? The L444P/L444P genotype was thought to be associated with neurological disease. Two type I patients with this genotype who exhibited no central nervous system disease were identified, however. The R463C and c1263del mutations were found to be present at a higher frequency than reported in other populations and they should be included in any mutation screen of this population. The recombinant mutations RecA456P and c1263del+RecTL have not been previously described and are the fourth and fifth recombinant mutations identified in the glucocerebrosidase gene.
Zebrafish embryo screen for mycobacterial genes involved in the initiation of granuloma formation reveals a newly identified ESX-1 component

SUMMARY The hallmark of tuberculosis (TB) is the formation of granulomas, which are clusters of infected macrophages surrounded by additional macrophages, neutrophils and lymphocytes. Although it has long been thought that granulomas are beneficial for the host, there is evidence that mycobacteria also promote the formation of these structures. In this study, we aimed to identify new mycobacterial factors involved in the initial stages of granuloma formation. We exploited the zebrafish embryo Mycobacterium marinum infection model to study initiation of granuloma formation and developed an in vivo screen to select for random M. marinum mutants that were unable to induce granuloma formation efficiently. Upon screening 200 mutants, three mutants repeatedly initiated reduced granuloma formation. One of the mutants was found to be defective in the espL gene, which is located in the ESX-1 cluster. The ESX-1 cluster is disrupted in the Mycobacterium bovis BCG vaccine strain and encodes a specialized secretion system known to be important for granuloma formation and virulence. Although espL has not been implicated in protein secretion before, we observed a strong effect on the secretion of the ESX-1 substrates ESAT-6 and EspE. We conclude that our zebrafish embryo M. marinum screen is a useful tool to identify mycobacterial genes involved in the initial stages of granuloma formation and that we have identified a new component of the ESX-1 secretion system. We are confident that our approach will contribute to the knowledge of mycobacterial virulence and could be helpful for the development of new TB vaccines.
Acute smoking increases ST depression in humans during general anesthesia.

UNLABELLED We tested the hypothesis that acute smoking is associated with ST segment depression during general anesthesia in patients without ischemic heart disease. The carbon monoxide (CO) concentration in expired gas and hemodynamic data was measured during general anesthesia for noncardiac or nonperipheral vascular surgery in patients without symptoms or evidence of ischemic heart disease. Increased expired CO concentrations are indicators of recent smoking. Logistic regression analysis identified significant predictors of ST segment depression > or = 1 mm. Both rate pressure product (odds ratio 1.20 for each increase of 1000, 95% confidence interval = 1.04-1.41, P = 0.007) and expired CO concentration (odds ratio 1.05 for each part per million increase, 95% confidence interval = 1.03-1.08, P = 0.001) were significant predictors of ST segment depression when considered simultaneously. Males demonstrated a lower probability of having an episode of ST depression (odds ratio = 0.16, P = 0.01), but this did not change the relationship between rate pressure product and CO as predictors of ST depression. Approximately 25% of chronically smoking patients smoked on the morning of surgery despite instructions not to smoke. IMPLICATIONS Patients under age 65 without symptoms of ischemic heart disease who smoked shortly before surgery had more episodes of rate pressure product-related ST segment depression than nonsmokers, prior smokers, or chronic smokers who did not smoke before surgery. Females were at greater risk of ST depression than males.
Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis

Background Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent. Methods A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. Results Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 – 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 – 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 – 2.049), Japan (OR = 0.812; 95%CI = 0.545 – 1.211), and Korea (OR = 1.056; 95%CI = 0.727 – 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 – .094) and Korea (OR = 1.914; 95%CI = 1.311 – 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 – 1.321). Conclusion In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.
Deformation‐based nuclear morphometry: Capturing nuclear shape variation in HeLa cells

The empirical characterization of nuclear shape distributions is an important unsolved problem with many applications in biology and medicine. Numerous genetic diseases and cancers have alterations in nuclear morphology, and methods for characterization of morphology could aid in both diagnoses and fundamental understanding of these disorders. Automated approaches have been used to measure features related to the size and shape of the cell nucleus, and statistical analysis of these features has often been performed assuming an underlying Euclidean (linear) vector space. We discuss the difficulties associated with the analysis of nuclear shape in light of the fact that shape spaces are nonlinear, and demonstrate methods for characterizing nuclear shapes and shape distributions based on spatial transformations that map one nucleus to another. By combining large deformation metric mapping with multidimensional scaling we offer a flexible approach for elucidating the intrinsic nonlinear degrees of freedom of a distribution of nuclear shapes. More specifically, we demonstrate approaches for nuclear shape interpolation and computation of mean nuclear shape. We also provide a method for estimating the number of free parameters that contribute to shape as well as an approach for visualizing most representative shape variations within a distribution of nuclei. The proposed methodology can be completely automated, is independent of the dimensionality of the images, and can handle complex shapes. Results obtained by analyzing two sets of images of HeLa cells are shown. In addition to identifying the modes of variation in normal HeLa nuclei, the effects of lamin A/C on nuclear morphology are quantitatively described. © 2007 International Society for Analytical Cytology
CONVERGENCE IN EXPONENTIABLE SPACES

Exponentiable spaces are characterized in terms of convergence. More precisely, we prove that a relation R : UX ⇀ X between ultrafilters and elements of a set X is the convergence relation for a quasi-locally-compact (that is, exponentiable) topology on X if and only if the following conditions are satisfied: 1. id ⊆ R ◦ η 2. R ◦ UR = R ◦ μ where η : X → UX and μ : U(UX) → UX are the unit and the multiplication of the ultrafilter monad, and U : Rel → Rel extends the ultrafilter functor U : Set → Set to the category of sets and relations. (U , η, μ) fails to be a monad on Rel only because η is not a strict natural transformation. So, exponentiable spaces are the lax (with respect to the unit law) algebras for a lax monad on Rel . Strict algebras are exponentiable and T1 spaces.
Impact of Surface Waves on SWOT's Projected Ocean Accuracy

The Surface Water and Ocean Topography (SWOT) mission being considered by NASA has, as one of its main objectives, to measure ocean topography with centimeter scale accuracy over kilometer scale spatial resolution. This paper investigates the impact of ocean waves on SWOT’s projected performance. Several effects will be examined: volumetric decorrelation, aliasing of ocean waves, backscattering modulation, and the so-called surfboard sampling.
Evaluation of calf starters containing different amounts of crude protein for growth of Holstein calves.

Holstein calves (n = 110) were used to evaluate the effect of calf starters containing 15, 16.8, 19.6, or 22.4% CP, DM basis (diets A, B, C, and D, respectively), on calf performance from d 4 to 56 of life. Preweaning daily gain tended to increase linearly as protein content of diets increased, averaging . 37, . 39, . 38, and . 44 kg/d for diets A, B, C, and D, respectively. After weaning, calves fed diet C gained the most (.86 versus .71, .75, and .79 kg/d for A, B, and D, respectively). Overall BW gains from d 4 to 56 averaged . 54, . 56, . 62, and . 61 kg/d for A, B, C, and D, respectively. Throughout the experiment, starter consumption tended to increase as CP content of diet increased. Under these conditions, maximum growth was supported by diet C (19.6% CP); no advantage was gained from higher (22.4%) protein content. Calf growth was moderate when calf starters of lower protein contents (15 or 16.8%) were fed.
Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants

Background & Aims Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV) are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster. Methods Dutch infants (n = 132) were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes. Results One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs) for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group. Conclusion Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA) and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are important for PCV evaluation. How differences between the two vaccines relate to long-term protection requires further investigation. Trial Registration www.trialregister. nl NTR3069
Xanthomonas campestris Overcomes Arabidopsis Stomatal Innate Immunity through a DSF Cell-to-Cell Signal-Regulated Virulence Factor1[OA]

Pathogen-induced stomatal closure is part of the plant innate immune response. Phytopathogens using stomata as a way of entry into the leaf must avoid the stomatal response of the host. In this article, we describe a factor secreted by the bacterial phytopathogen Xanthomonas campestris pv campestris (Xcc) capable of interfering with stomatal closure induced by bacteria or abscisic acid (ABA). We found that living Xcc, as well as ethyl acetate extracts from Xcc culture supernatants, are capable of reverting stomatal closure induced by bacteria, lipopolysaccharide, or ABA. Xcc ethyl acetate extracts also complemented the infectivity of Pseudomonas syringae pv tomato (Pst) mutants deficient in the production of the coronatine toxin, which is required to overcome stomatal defense. By contrast, the rpfF and rpfC mutant strains of Xcc, which are unable to respectively synthesize or perceive a diffusible molecule involved in bacterial cell-to-cell signaling, were incapable of reverting stomatal closure, indicating that suppression of stomatal response by Xcc requires an intact rpf/diffusible signal factor system. In addition, we found that guard cell-specific Arabidopsis (Arabidopsis thaliana) Mitogen-Activated Protein Kinase3 (MPK3) antisense mutants were unresponsive to bacteria or lipopolysaccharide in promotion of stomatal closure, and also more sensitive to Pst coronatine-deficient mutants, showing that MPK3 is required for stomatal immune response. Additionally, we found that, unlike in wild-type Arabidopsis, ABA-induced stomatal closure in MPK3 antisense mutants is not affected by Xcc or by extracts from Xcc culture supernatants, suggesting that the Xcc factor might target some signaling component in the same pathway as MPK3.