Miracle-dz/UniFAR-FTUs huggingface dataset:
A natural polymorphism of Mycobacterium tuberculosis in the esxH gene disrupts immunodomination by the TB10.4-specific CD8 T cell response

CD8 T cells provide limited protection against Mycobacterium tuberculosis (Mtb) infection in the mouse model. As Mtb causes chronic infection in mice and humans, we hypothesize that Mtb impairs T cell responses as an immune evasion strategy. TB10.4 is an immunodominant antigen in people, nonhuman primates, and mice, which is encoded by the esxH gene. In C57BL/6 mice, 30–50% of pulmonary CD8 T cells recognize the TB10.44−11 epitope. However, TB10.4-specific CD8 T cells fail to recognize Mtb-infected macrophages. We speculate that Mtb elicits immunodominant CD8 T cell responses to antigens that are inefficiently presented by infected cells, thereby focusing CD8 T cells on nonprotective antigens. Here, we leverage naturally occurring polymorphisms in esxH, which frequently occur in lineage 1 strains, to test this “decoy hypothesis”. Using the clinical isolate 667, which contains an EsxHA10T polymorphism, we observe a drastic change in the hierarchy of CD8 T cells. Using isogenic Erd.EsxHA10T and Erd.EsxHWT strains, we prove that this polymorphism alters the hierarchy of immunodominant CD8 T cell responses. Our data are best explained by immunodomination, a mechanism by which competition for APC leads to dominant responses suppressing subdominant responses. These results were surprising as the variant epitope can bind to H2-Kb and is recognized by TB10.4-specific CD8 T cells. The dramatic change in TB10.4-specific CD8 responses resulted from increased proteolytic degradation of A10T variant, which destroyed the TB10.44-11epitope. Importantly, this polymorphism affected T cell priming and recognition of infected cells. These data support a model in which nonprotective CD8 T cells become immunodominant and suppress subdominant responses. Thus, polymorphisms between clinical Mtb strains, and BCG or H37Rv sequence-based vaccines could lead to a mismatch between T cells that are primed by vaccines and the epitopes presented by infected cells. Reprograming host immune responses should be considered in the future design of vaccines.
Role of machine learning in gait analysis: a review

Abstract Human biomechanics and gait form an integral part of life. The gait analysis involves a large number of interdependent parameters that were difficult to interpret due to a vast amount of data and their inter-relations. To simplify evaluation, the integration of machine learning (ML) with biomechanics is a promising solution. The purpose of this review is to familiarise the readers with key directions of implementation of ML techniques for gait analysis and gait rehabilitation. An extensive literature survey was based on research articles from nine databases published from 1980 to 2019. With over 943 studies identified, finally, 43 studies met the inclusion criteria. The outcome reported illustrates that supervised ML techniques showed accuracies above 90% in the identified gait analysis domain. The statistical results revealed support vector machine (SVM) as the best classifier (mean-score = 0.87 ± 0.07) with remarkable generalisation capability even on small to medium datasets. It has also been analysed that the control strategies for gait rehabilitation are benefitted from reinforcement learning and (deep) neural-networks due to their ability to capture participants’ variability. This review paper shows the success of ML techniques in detecting disorders, predicting rehabilitation length, and control of rehabilitation devices which make them suitable for clinical diagnosis.
Association between Neighborhood Food Access, Household Income, and Purchase of Snacks and Beverages in the United States

Considerable research on the risk factors of obesity and chronic diseases has focused on relationships between where people live, where they shop, and the types of food they purchase. Rarely have investigators used a national sample and explicitly addressed the amount of energy-dense and nutrient-poor foods purchased in different types of neighborhood food stores. Even more rarely have studies accounted for the characteristics of the broader built environment in which food stores are located and which affect the convenience of using neighborhood food stores. We used a large population-based cohort of predominantly white U.S. households from the Nielsen Homescan Consumer Panel 2010 dataset to examine whether there were positive cross-sectional associations between availability of neighborhood convenience stores and supermarkets and self-reported household annual expenditures for snacks and beverages. We examined this relationship separately for poor and non-poor households as defined by the 2010 U.S. federal poverty threshold. We used mixed error-component regression models to examine associations between availability of neighborhood food stores and the expenditures on snacks and beverages, controlling for regional destination accessibility, availability and diversity of neighborhood destinations, and neighborhood street connectivity. In multivariate analyses, we observed that poor households in neighborhoods with few convenience stores purchased more snacks than poor households in neighborhoods with many convenience stores (b = −0.008, p < 0.05). Non-poor households in neighborhoods with many convenience stores and fewer supermarkets purchased more snacks than non-poor households in neighborhoods with few convenience stores and many supermarkets (b = 0.002, p < 0.05 for convenience stores; b = −0.027, p < 0.05 for supermarkets). Increase in number of convenience stores decreased the purchase of snacks by poor households, but increased in non-poor households. On other hand, increase in number of supermarkets discouraged purchase of snacks by non-poor households but had no effect on the purchasing behavior of the poor-households.Therefore, evaluation of access to energy-dense and nutrient-poor foods should include a consideration of geographic proximity. Local governments should consider strategies to expand the availability and access to nutrient-rich food and beverage products in convenience stores for consumers.
High genetic diversity and presence of genetic structure characterise the Corso-Sardinian endemics Ruta corsica and Ruta lamarmorae (Rutaceae)

Corsica and Sardinia form one of the ten areas with highest biodiversity in the Mediterranean and are considered one of the priority regions for conservation in Europe. In order to preserve the high levels of endemism and biological diversity at different hierarchical levels, knowledge of the evolutionary history and current genetic structure of Corso-Sardinian endemics is instrumental. Microsatellite markers were newly developed and used to study the genetic structure and taxonomic status of Ruta corsica and Ruta lamarmorae, rare endemics of Corsica and Sardinia, respectively, and previously considered a single species. Our analyses identified high levels of genetic variation within each species (P=0.883, He=0.543 for R. corsica; P=0.972, He=0.627 for R. lamarmorae). Intrinsic traits of the species (hermaphroditism, proterandry and polyploidy) and island-dependent factors (i.e. age, origin and history of the islands) might explain the detected high levels of genetic variation. We discovered differentiation between R. corsica and R. lamarmorae, and genetic structure within each species, which are consistent with the observation of low dispersal ability for both species. Our genetic results support the recent taxonomic classification of R. corsica and R. lamarmorae as separate species and suggest that they diverge at only few loci. One R. corsica population (SA) strongly differed from all other studied populations and appeared to be the product of hybridization between the two species in STRUCTURE analyses. Our results provide important insights for the conservation of the two rare endemics. Further genetic analyses are recommended for R. lamarmorae and for population SA (R. corsica).
Experiences With Three-dimensional Printing in Complex Liver Surgery

Supplemental Digital Content is available in the text Objective: We present a series of cases where we used 3D printing in planning of complex liver surgery. Background: In liver surgery, three-dimensional reconstruction of the liver anatomy, in particular of vascular structures, has shown to be helpful in operation planning. So far, 3D printing has been used for medical applications only rarely. Methods and Patients: From December 2017 to December 2019, in 10 cases where surgery was assumed to be challenging operation planning was performed using full size 3D prints in addition to standard 3 phase CT scans. Models included transparent parenchyma, hepatic veins, vena cava, portal vein, hepatic artery, (biliary tree if requested), and tumors. In 7/10 cases vascular reconstructions were needed during the procedure. Nonstructured feedback of the surgical team revealed that the major benefit was visualization of the critical areas of vascular reconstruction, the expected dimensions of tangential vascular infiltration and the planning of reconstruction. In the multifocal tumors, 3D prints were considered to be helpful for intraoperative orientation to detect metastases and to improve planning of the resection. Conclusions: In complex liver surgery with potential need for vascular reconstructions operation planning may be optimized using a 3D printed liver model. Prospective studies are needed to evaluate the clinical impact of 3D printing in liver surgery compared to other 3D visualizations.
Immunotoxin Screening System: A Rapid and Direct Approach to Obtain Functional Antibodies with Internalization Capacities

Toxins, while harmful and potentially lethal, have been engineered to develop potent therapeutics including cytotoxins and immunotoxins (ITs), which are modalities with highly selective targeting capabilities. Currently, three cytotoxins and IT are FDA-approved for treatment of multiple forms of hematological cancer, and additional ITs are tested in the clinical trials or at the preclinical level. For next generation of ITs, as well as antibody-mediated drug delivery systems, specific targeting by monoclonal antibodies is critical to enhance efficacies and reduce side effects, and this methodological field remains open to discover potent therapeutic monoclonal antibodies. Here, we describe our application of engineered toxin termed a cell-based IT screening system. This unique screening strategy offers the following advantages: (1) identification of monoclonal antibodies that recognize cell-surface molecules, (2) selection of the antibodies that are internalized into the cells, (3) selection of the antibodies that induce cytotoxicity since they are linked with toxins, and (4) determination of state-specific activities of the antibodies by differential screening under multiple experimental conditions. Since the functional monoclonal antibodies with internalization capacities have been identified successfully, we have pursued their subsequent modifications beyond antibody drug conjugates, resulting in development of immunoliposomes. Collectively, this screening system by using engineered toxin is a versatile platform, which enables straight-forward and rapid selection for discovery of novel functional antibodies.
Comparing Occupational Adaptation-Based and Traditional Training Programs for Dementia Care Teams: An Embedded Mixed-Methods Study.

BACKGROUND AND OBJECTIVES With growing demand for a dementia-capable workforce, attention shifts from disseminating knowledge of care strategies to facilitating teams translating knowledge in practice. Occupational Adaptation (OA) is a theoretical framework used to facilitate people resolving real-world challenges through active problem solving, using relative mastery as its measure. This pilot study evaluated if and how OA-based training improves dementia care teams' relative mastery and team development more than a skills-based (SB) program. RESEARCH DESIGN AND METHODS We report results of an embedded mixed-methods study with 28 employees of a continuing care retirement community (two groups randomly assigned to nine-week programs). Data collection entailed two surveys conducted pre, mid, and post-intervention; observations; journals; and follow-up interviews. We extended beyond quantitative and qualitative analyses with cross-cutting analyses exploring exemplar and exceptional cases. RESULTS The OA group reported significantly greater improvements in relative mastery and team development (p < .05). Qualitative data supported the statistical findings and illuminated processes that led OA to out-perform SB. OA participants, those who analyzed real cases and alternated collaborative planning with cooperative action, were more likely to indicate pre-post differences in relative mastery and team development. DISCUSSION AND IMPLICATIONS We identified features of the OA program that diverse participants deemed effective; features that suggest how OA could underpin clinically relevant learning for workers. Further research is required to develop evidence of clinical effectiveness; however, our findings have relevance for agencies wishing to promote knowledge translation and collaborative problem solving in dementia workforce training.
Association of Health Literacy and Nutritional Status Assessment with Glycemic Control in Adults with Type 2 Diabetes Mellitus

While the role of medical and nutrition factors on glycemic control among adults with type 2 diabetes mellitus (T2DM) has been well-established, the association between health literacy (H.L.) and glycemic control is inconsistent. This study aims to determine the association of H.L. and nutritional status assessments with glycemic control in adults with type 2 diabetes mellitus. A total of 280 T2DM respondents (mean (SD) age = 49.7 (10.3) years, Glycated hemoglobin (HbA1c) = 9.9 (2.6) %, and Body Mass Index = 32.7 (15.1) kg/m2) were included in this study. A short-form Test of Functional Health Literacy in Adults (S-TOFHLA) assessed the H.L. levels. Nutritional status assessments included client history, glycemic control, anthropometric, and biochemical data. The mean (S.D.) H.L. score was 45.7 (24.6), with 56% of the respondents had inadequate H.L. Inadequate H.L. was more common among those females; housewives, low education, received oral antidiabetic therapy, and shorter diabetes duration. Respondents with inadequate H.L. were significantly older and had higher HbA1c than those with marginal and adequate H.L. Meanwhile, respondents with inadequate and marginal H.L. levels had significantly higher total cholesterol, LDL-cholesterol, and systolic blood pressure than the respondents with adequate H.L. Low H.L. scores, self-employment status, received dual antidiabetic therapy (insulin with oral agents), received insulin alone, and had higher fasting blood glucose explained about 21% of the total variation in HbA1c (adjusted R2 = 0.21; p < 0.001). Respondents with inadequate H.L. had poor glycemic control. The H.L. scores, together with nutritional status assessments, were the factors that predicted poor glycemic control among adults with T2DM.
Antibody Opsonization Enhances Early Interactions between Yersinia pestis and Neutrophils in the Skin and Draining Lymph Node in a Mouse Model of Bubonic Plague

Bubonic plague results when Yersinia pestis is deposited in the skin via the bite of an infected flea. Bacteria then traffic to the draining lymph node (dLN) where they replicate to large numbers. Without treatment, this infection can result in highly fatal septicemia. Several plague vaccine candidates are currently at various stages of development, but no licensed vaccine is available in the United States. Though polyclonal and monoclonal antibodies (Ab) can provide complete protection against bubonic plague in animal models, the mechanisms responsible for this antibody-mediated immunity (AMI) to Y. pestis remain poorly understood. ABSTRACT Bubonic plague results when Yersinia pestis is deposited in the skin via the bite of an infected flea. Bacteria then traffic to the draining lymph node (dLN) where they replicate to large numbers. Without treatment, this infection can result in highly fatal septicemia. Several plague vaccine candidates are currently at various stages of development, but no licensed vaccine is available in the United States. Though polyclonal and monoclonal antibodies (Ab) can provide complete protection against bubonic plague in animal models, the mechanisms responsible for this antibody-mediated immunity (AMI) to Y. pestis remain poorly understood. Here, we examine the effects of Ab opsonization on Y. pestis interactions with phagocytes in vitro and in vivo. Opsonization of Y. pestis with polyclonal antiserum modestly increased phagocytosis/killing by an oxidative burst of murine neutrophils in vitro. Intravital microscopy (IVM) showed increased association of Ab-opsonized Y. pestis with neutrophils in the dermis in a mouse model of bubonic plague. IVM of popliteal LNs after intradermal (i.d.) injection of bacteria in the footpad revealed increased Y. pestis-neutrophil interactions and increased neutrophil crawling and extravasation in response to Ab-opsonized bacteria. Thus, despite only having a modest effect in in vitro assays, opsonizing Ab had a dramatic effect in vivo on Y. pestis-neutrophil interactions in the dermis and dLN very early after infection. These data shed new light on the importance of neutrophils in AMI to Y. pestis and may provide a new correlate of protection for evaluation of plague vaccine candidates.
Challenges to Achieving Measles Elimination, Georgia, 2013–2018

Controlling measles outbreaks in the country of Georgia and throughout Europe is crucial for achieving the measles elimination goal for the World Health Organization’s European Region. However, large-scale measles outbreaks occurred in Georgia during 2013–2015 and 2017–2018. The epidemiology of these outbreaks indicates widespread circulation and genetic diversity of measles viruses and reveals persistent gaps in population immunity across a wide age range that have not been sufficiently addressed thus far. Historic problems and recent challenges with the immunization program contributed to outbreaks. Addressing population susceptibility across all age groups is needed urgently. However, conducting large-scale mass immunization campaigns under the current health system is not feasible, so more selective response strategies are being implemented. Lessons from the measles outbreaks in Georgia could be useful for other countries that have immunization programs facing challenges related to health-system transitions and the presence of age cohorts with historically low immunization coverage.
Negative affect interference and fear of happiness are independently associated with depressive symptoms.

OBJECTIVES Reward devaluation theory (RDT) posits that some depressed individuals avoid positivity due to its previous association with negative outcomes. Behavioral indicators of avoidance of reward support RDT, but self-report indicators have yet to be examined discriminantly. Two candidate self-report measures were examined in relation to depression: negative affect interference (NAI), or the experience of negative affect in response to positivity, and fear of happiness, a fear of prospective happiness. METHOD Participants completed measures assessing NAI, fear of happiness scale, and depression online via Amazon's Mechanical Turk at three time points (N = 375). Multilevel modeling examined the relationship between NAI, fear of happiness, and depressive symptoms longitudinally. RESULTS NAI and fear of happiness were both positively associated with depressive symptoms. They both uniquely predicted depressive symptoms when included within the same model. CONCLUSIONS These findings suggest that different conceptualizations of positivity avoidance are uniquely associated with depressive symptoms.
Multidrug-Resistant Hypervirulent Group B Streptococcus in Neonatal Invasive Infections, France, 2007–2019

We analyzed group B Streptococcus (GBS) neonatal invasive infections reported during 2007–2019 in France. The hypervirulent clonal complex (CC) 17 GBS was responsible for 66% (827/1,262) of cases. The role of CC17 GBS increased over time (p for trend = 0.0001), together with the emergence of a multidrug-resistant CC17 GBS sublineage.
Genetic architecture of collective behaviors in zebrafish

Collective behaviors of groups of animals, such as schooling and shoaling of fish, are central to species survival, but genes that regulate these activities are not known. Here we parsed collective behavior of groups of adult zebrafish using computer vision and unsupervised machine learning into a set of highly reproducible, unitary, several hundred millisecond states and transitions, which together can account for the entirety of relative positions and postures of groups of fish. Using CRISPR-Cas9 we then targeted for knockout 35 genes associated with autism and schizophrenia. We found mutations in three genes had distinctive effects on the amount of time spent in the specific states or transitions between states. Mutation in immp2l (inner mitochondrial membrane peptidase 2-like gene) enhances states of cohesion, so increases shoaling; mutation in in the Nav1.1 sodium channel, scn1lab+/− causes the fish to remain scattered without evident social interaction; and mutation in the adrenergic receptor, adra1aa−/−, keeps fish close together and retards transitions between states, leaving fish motionless for long periods. Motor and visual functions seemed relatively well-preserved. This work shows that the behaviors of fish engaged in collective activities are built from a set of stereotypical states. Single gene mutations can alter propensities to collective actions by changing the proportion of time spent in these states or the tendency to transition between states. This provides an approach to begin dissection of the molecular pathways used to generate and guide collective actions of groups of animals.
Stegana (Oxyphortica) convergens species group (Diptera: Drosophilidae) from the Oriental region, with morphological and molecular evidence

ABSTRACT Three new species of the Stegana (Oxyphortica) convergens species group are described from South China: S. (O.) gonglui Wang and Chen, sp. nov., S. (O.) xiaoyangae Zhang and Chen, sp. nov., and S. (O.) zhulinae Wang and Chen, sp. nov. The diagnosis of S. (O.) setifrons is revised. A key to all eight species of this group is provided. The phylogenetic relationships among the eight species of this group are reconstructed using DNA sequences of the mitochondrial COI gene (cytochrome c oxidase, subunit I). The intra- and interspecific pairwise Kimura’s two-parameter (K-2P) distances for these species are summarised. Moreover, 35 COI sequences of the eight convergens species show the presence of 30 species-specific base substitutions in 28 nucleotide sites in the character-based analysis. www.zoobank.org/urn:lsid:zoobank.org:pub:8AC2D398-96F2-4EE5-AE0D-16B8761BD55D