Miracle-dz/UniFAR-FTUs huggingface dataset:
Brucella Egresses from Host Cells Exploiting Multivesicular Bodies

How intracellular bacterial pathogens egress from host cells has been poorly studied. This is particularly important because this stage of the infectious cycle can have a strong impact on how the host resolves the infection. Brucella is an intracellular pathogen that infects mammals, including humans, and causes a chronic debilitating illness. ABSTRACT Host cell egress is a critical step in the life cycle of intracellular pathogens, especially in microbes capable of establishing chronic infections. The Gram-negative bacterium Brucella belongs to such a group of pathogens. Even though much has been done to understand how Brucella avoids killing and multiplies in its intracellular niche, the mechanism that this bacterium deploys to egress from the cell to complete its cycle has been poorly studied. In the manuscript, we quantify the kinetics of bacterial egress and show that Brucella exploits multivesicular bodies to exit host cells. For the first time, we visualized the process of egress in real time by live video microscopy and showed that a population of intracellular bacteria exit from host cells in vacuoles containing multivesicular body-like features. We observed the colocalization of Brucella with two multivesicular markers, namely, CD63 and LBPA, both during the final stages of the intracellular life cycle and in egressed bacteria. Moreover, drugs that either promote or inhibit multivesicular bodies either increased or decreased the number of extracellular bacteria, respectively. Our results strongly suggest that Brucella hijacks multivesicular bodies to exit the host cells to initiate new infection events. IMPORTANCE How intracellular bacterial pathogens egress from host cells has been poorly studied. This is particularly important because this stage of the infectious cycle can have a strong impact on how the host resolves the infection. Brucella is an intracellular pathogen that infects mammals, including humans, and causes a chronic debilitating illness. The bacterium has evolved a plethora of mechanisms to invade host cells, avoid degradation in the endocytic pathway, and actively multiply within a specialized intracellular compartment. However, how this pathogen exits from infected cells to produce reinfection and complete its life cycle is poorly understood. In the manuscript, we shed some light on the mechanisms that are exploited by Brucella to egress from host cells. We observed for the first time the egress of Brucella from infected cells by time-lapse video microscopy, and we found that the bacterium exits in vesicles containing multivesicular bodies (MVBs) features. Moreover, the drug manipulation of MVBs resulted in the alteration of bacterial egress efficiency. Our results indicate that Brucella hijacks MVBs to exit host cells and that this strongly contributes to the reinfection cycle.
Differences in firearm storage practices among United States military servicemembers who have and have not disclosed suicidal thoughts or attended behavioral health sessions.

INTRODUCTION Two-thirds of military suicides are by firearm, and unsafe storage increases the risk of suicide. Understanding who is at risk for suicide, their interactions with behavioral healthcare, and their firearm storage habits have implications for suicide prevention. METHOD Probability-based sampling was used. Inclusion criteria were current military service and firearm ownership. Analyses focused on those who endorsed past year (n = 180) or past month suicidal ideation (n = 85). RESULTS Servicemembers with undisclosed past year ideation stored firearms at home more often and with a locking device less often. Servicemembers with past year ideation who did not attend recent behavioral health sessions stored firearms with a locking device and loaded less often. Servicemembers with undisclosed suicidal ideation in the past month stored firearms with a locking device less often. Servicemembers with past month ideation who have not attended recent behavioral health sessions stored firearms with a locking device and loaded less often. CONCLUSIONS Servicemembers experiencing undisclosed suicidal ideation and who are not receiving treatment generally have more ready access to firearms. Safe firearm storage messaging needs to be disseminated in a manner that shifts social norms around firearm storage, whether or not suicide risk is known.
Seasonality and other risk factors for fleas infestations in domestic dogs and cats

Fleas in the genus Ctenocephalides are the most clinically important parasitic arthropods of dogs and cats worldwide yet risk factors that might increase the risk of infestation in small animals remains unclear. Here we developed a supervised text mining approach analysing key aspects of flea epidemiology using electronic health records from domestic cats and dogs seen at a sentinel network of 191 voluntary veterinary practices across Great Britain between March 2014 and July 2020. Our methods identified fleas as likely to have been present during 22,276 of 1,902,016 cat consultations (1.17%) and 12,168 of 4,844,850 dog consultations (0.25%). Multivariable logistic regression modelling found that animals originating from areas of least deprivation were associated with 50% reductions in odds of veterinary‐recorded flea infestation compared to the most deprived regions in England. Age of the animal was significantly associated with flea presentation in both cats and dogs, with cases peaking before animals reached 12 months. Cases were recorded through each study years, peaking between July and October, with fluctuations between each year. Our findings can be used towards healthcare messaging for veterinary practitioners and owners.
Decoding the radiomic features of dorsolateral prefrontal cortex in individuals with accelerated cortical changes: implications for personalized transcranial magnetic stimulation

Abstract. Purpose Image-guided transcranial magnetic stimulation (TMS) is an emerging research field in neuroscience and rehabilitation medicine. Cortical morphometry, as a radiomic phenotype of aging, plays a vital role in developing personalized TMS model, yet few studies are afoot to examine the aging effects on region-specific morphometry and use it in the estimation of TMS-induced electric fields. Our study was aimed to investigate the radiomic features of bilateral dorsolateral prefrontal cortex (DLPFC) and quantify the TMS-induced electric fields during aging. Approach Baseline, 1-year and 3-year structural magnetic resonance imaging (MRI) scans from normal aging (NA) adults (n = 32) and mild cognitive impairment (MCI) converters (n = 22) were drawn from the Open Access Series of Imaging Studies. The quantitative measures of radiomics included cortical thickness, folding, and scalp-to-cortex distance. Realistic head models were developed to simulate the impacts of radiomic features on TMS-induced E-fields using the finite-element method. Results A pronounced aging-related decrease was found in the gyrification of left DLPFC in MCI converters (t = 2.21, p = 0.035), which could predict the decline of global cognition at 3-year follow up. Along with the decreased gyrification in left DLPFC, the magnitude of TMS-induced E-fields was rapidly decreased in MCI converters (t = 2.56, p = 0.018). Conclusions MRI-informed radiomic features of the treatment targets have significant effects on the intensity and distribution of the stimulation-induced electric fields in prodromal dementia patients. Our findings highlight the importance of region-specific radiomics when conducting the transcranial brain stimulation in individuals with accelerated cortical changes, such as Alzheimer’s disease.
On a variance stabilizing model and its application to genomic data

In this paper, we propose a model based on a class of symmetric distributions, which avoids the transformation of data, stabilizes the variance of the observations, and provides robust estimation of parameters and high flexibility for modeling different types of data. Probabilistic and statistical aspects of this new model are developed throughout the article, which include mathematical properties, estimation of parameters and inference. The obtained results are illustrated by means of real genomic data.
One fifth of patients with Achilles tendinopathy have symptoms after 10 years: A prospective cohort study

ABSTRACT Patients with midportion Achilles tendinopathy (AT) are thought to experience a gradual symptomatic improvement over time. The aim of this study was to prospectively investigate if patients with midportion AT have symptoms at 10-year follow-up. Patients withmidportion AT were invited to complete an online questionnaire 10 years after inclusion in an intervention trial. The primary outcomewas the presence of AT symptoms. Secondary outcomes were: the Victorian Institute of Sports Assessment-Achilles tendinopathy (VISA-A, 0–100) score and sports activity level. Of the 54 patientsincluded, 43 (80%) completed the questionnaire at an average follow-up of 10.4 years. Persisting symptoms were reported by 19%. The mean (standard deviation-SD) VISA-A score improved from 52 (17) at baseline to 79 (21) at 10-years follow-up with a mean change of 27 points (95% confidence interval: 21; 35, p < 0.001). Of the 38 active patients, 16 (42%) returned to their pre-injury level sports,of whom 14 (37%) performed them pain free. One-fifth of patients with conservatively treated midportion AT still have symptoms after 10years. One-third of patients were able to perform sports pain-free atpre-injury level. Patients should be adequately counselled to giverealistic expectations. Trial registration number: clinicaltrials.gov (identifier: NCT00761423).
Genomic and Transcriptomic Insights into Salinity Tolerance-Based Niche Differentiation of Synechococcus Clades in Estuarine and Coastal Waters

Synechococcus is a group of unicellular Cyanobacteria that are widely distributed in global aquatic ecosystems. Salinity is a factor that affects the distribution of microorganisms in estuarine and coastal environments. ABSTRACT Cluster 5 Synechococcus is one of the most important primary producers on earth. However, ecotypes of this genus exhibit complex geographical distributions, and the genetic basis of niche partitioning is still not fully understood. Here, we report distinct distributions of subcluster 5.1 (SC5.1) and subcluster 5.2 (SC5.2) Synechococcus in estuarine waters, and we reveal that salinity is the main factor determining their distribution. Clade III (belonging to SC5.1) and CB4 (belonging to SC5.2) are dominant clades in the study region, with different ecological distributions. We further conducted physiological, genomic, and transcriptomic studies of Synechococcus strains YX04-3 and HK05, which are affiliated with clade III and CB4, respectively. Laboratory tests showed that HK05 could grow at low salinity (13 ppt), whereas the growth of YX04-3 was suppressed when salinity decreased to 13 ppt. Genomic and transcriptomic analysis suggested that euryhaline clade CB4 is capable of dealing with a sudden drop of salinity by releasing compatible solutes through mechanosensitive channels that are coded by the mscL gene, decreasing biosynthesis of organic osmolytes, and increasing expression of heat shock proteins and high light-inducible proteins to protect photosystem. Furthermore, CB4 strain HK05 exhibited a higher growth rate when growing at low salinity than at high salinity. This is likely achieved by reducing its biosynthesis of organic osmolyte activity and increasing its photosynthetic activity at low salinity, which allowed it to enhance the assimilation of inorganic carbon and nitrogen. Together, these results provide new insights regarding the ecological distribution of SC5.2 and SC5.1 ecotypes and their underlying molecular mechanisms. IMPORTANCE Synechococcus is a group of unicellular Cyanobacteria that are widely distributed in global aquatic ecosystems. Salinity is a factor that affects the distribution of microorganisms in estuarine and coastal environments. In this study, we studied the distribution pattern of Synechococcus community along the salinity gradient in a subtropical estuary. By using omic methods, we unveiled genetic traits that determine the niche partitioning of euryhaline and strictly marine Synechococcus. We also explored the strategies employed by euryhaline Synechococcus to cope with a sudden drop of salinity, and revealed possible mechanisms for the higher growth rate of euryhaline Synechococcus in low salinity conditions. This study provides new insight into the genetic basis of niche partitioning of Synechococcus clades.
Risk factors associated with glycated hemoglobin A1c trajectories progressing to type 2 diabetes

Abstract Background and objective The notion of prediabetes, defined by the ADA as glycated hemoglobin A1c (HbA1c) of 5.7–6.4%, implies increased vascular inflammatory and immunologic processes and higher risk for developing diabetes mellitus and major cardiovascular events. We aimed to determine the risk factors associated with rapid progression of normal and prediabetes patients to type 2 diabetes mellitus (T2DM). Methods Retrospective cohort study in a single 8-hospital health system in southeast Michigan, between 2006 and 2020. All patients with HbA1c <6.5% at baseline and at least 2 other HbA1c measurements were clustered in five trajectories encompassing more than 95% of the study population. Multivariate linear regression analysis was performed to examine the association of demographic and comorbidities with HbA1c trajectories progressing to diabetes. Results A total of 5,347 prediabetic patients were clustered based on their HbA1c progression (C1: 4,853, C2: 253, C66: 102, C12: 85, C68: 54). The largest cluster (C1) had a baseline median HbA1c value of 6.0% and exhibited stable HbA1c levels in prediabetic range across all subsequent years. The smallest cluster (C68) had the lowest median baseline HbA1c value and also remained stable across subsequent years. The proportion of normal HbA1c in each of the pre-diabetic trajectories ranged from 0 to 12.7%, whereas 81.5% of the reference cluster (C68) were normal HbA1c at baseline. The C2 (steady rising) trajectory was significantly associated with BMI (adj OR 1.10, 95%CI 1.03–1.17), and family history of DM (adj OR 2.75, 95%CI 1.32–5.74). With respect to the late rising trajectories, baseline BMI was significantly associated with both C66 and C12 trajectory (adj OR 1.10, 95%CI 1.03–1.18) and (adj OR 1.13, 95%CI 1.05–1.23) respectively, whereas, the C12 trajectory was also significantly associated with age (adj OR 1.62, 95%CI 1.04–2.53) and history of MACE (adj OR 3.20, 95%CI 1.14–8.93). Conclusions We suggest that perhaps a more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c, whether they have normal hemoglobin A1c or they have prediabetes. KEY MESSAGES Progression to diabetes from normal or prediabetic hemoglobin A1c within four years is associated with baseline BMI. A steady rise in HbA1c during a four-year period is associated with age and family history of T2DM, whereas age and personal history of MACE are associated with a rapid rise in HbA1c. A more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c.
Predicting Treatment Responses in Patients With Osteoarthritis: Results From Two Phase III Tanezumab Randomized Clinical Trials

Prediction of treatment responses is essential to move forward translational science. Our question was to identify patient‐based variables that predicted responses to treatments. We conducted secondary analyses on pooled data from two randomized phase III clinical trials (NCT02697773 and NCT02709486) conducted in participants with moderate to severe osteoarthritis randomized to subcutaneous placebo (n = 514) or tanezumab 2.5 mg (n = 514). We used gradient boosted regression trees to identify variables that predicted Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale scores at Week 16 and marginal plots to determine the directional relationship between each variable category and responses to placebo or tanezumab within the models. We also used Virtual Twins models to identify potential subgroups of response to the active treatment vs. placebo. We found that responses to placebo were predicted by baseline WOMAC Physical Function, baseline WOMAC Pain, the radiographic classification of the index joint, and the standard deviation of diary pain scores at baseline. In contrast, baseline WOMAC Pain along with failure of prior medications, duration of disease, and standard deviation of diary pain scores at baseline were predictive of tanezumab responses as expressed by the WOMAC Pain scores at Week 16. Those who responded to tanezumab vs. placebo were identified based on the radiographic classification of the index joint and either age or smoking status. These secondary‐data analyses identified distinct and common patient‐based variables to predict response to placebo or tanezumab. These findings will inform the design of future clinical trials, helping to move forward clinical pharmacology and translational science.
Affective and cognitive impact of social overinclusion: a meta-analytic review of cyberball studies

ABSTRACT Belongingness is a central biopsychosocial system. Challenges to belongingness (i.e. exclusion/ostracism) engender robust negative effects on affect and cognitions. Whether overinclusion – getting more than one’s fair share of social attention – favourably impacts affect and cognitions remains an open question. This pre-registered meta-analysis includes twenty-two studies (N = 2757) examining overinclusion in the context of the Cyberball task. We found that the estimated overall effect size of overinclusion on positive affect was small but robust, and the effect on fundamental needs cognitions (belongingness, self-esteem, meaningful existence and control) was moderate in size and positive in direction. Notably, the effect sizes of overinclusion were smaller than the corresponding effects of exclusion. Finally, the effects of overinclusion on positive affect were greater for high, as compared to low, socially anxious individuals. Exploring the sequelae of the full range of inclusion experiences – from exclusion to overinclusion – may enrich our understanding of the functioning of the belongingness system as well as its interaction with another central biosocial system – the social status system.
ACOUSTIC GENERATION IN LIQUID CRYSTALS

In this letter, we report on the acoustic emission from liquid crystals during the electric switching of these materials. The initial observation of the sound was in a bistable nematic liquid crystal. This investigation revealed that a faint, but audible, sound is generated when a liquid crystal is switched from one state to another. We have undertaken a systematic study to investigate the origin of acoustic generation in these materials. By investigating the intensity and frequency of the sound emission, we have concluded that the sound originates as a result of molecular motion, which results in the excitation of the cavity containing the liquid crystal.
Degree of Accuracy With Which Deep Learning for Ultrasound Images Identifies Osteochondritis Dissecans of the Humeral Capitellum

Background: Medical screening using ultrasonography (US) has been performed on young baseball players for early detection of osteochondritis dissecans (OCD) of the humeral capitellum. Deep learning (DL) and artificial intelligence (AI) techniques are widely adopted in the medical imaging research field. Purpose/Hypothesis: The purpose of this study was to calculate the diagnostic accuracy using DL for US images of OCD. We hypothesized that using DL for US imaging would improve the prediction accuracy of OCD. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: A total of 40 elbows (mean age of patients, 12.1 years) that were suspected of having OCD at a medical checkup and later confirmed by radiographs and magnetic resonance imaging were included in the study. The affected elbows were used as the OCD group and the contralateral elbows as the control group. From US videos, 100 images per elbow were captured from different angles, and 4000 images of the elbows were prepared for both groups. Of these, 80% were randomly selected by DL models and used as training data; the remaining were used as test data. Transfer learning was conducted using 3 pretrained DL models. The confusion matrix and the area under the receiver operating characteristic curve (AUC) were used to evaluate the model, and the visualization of the areas deemed important by the DL models was also performed. Furthermore, OCD regions were detected using an automatic image recognition model based on DL. Results: Classification of the OCD image by the DL model was performed; the best accuracy score was 0.87; the recall was 1.00. AUC was high for all DL models. Visualization of important features showed that AI predicted the presence of OCD by focusing on the irregularity or discontinuity of the surface of subchondral bone. In the detection of OCD task, the mean average precision was 0.83. Conclusion: The DL on US images identified OCD with high accuracy. The important features detected by the DL models correspond to the areas used by clinicians in screening the US images. The OCD was also detected with high accuracy using the object detection model. The AI model may be used in medical screening for OCD.
Comparison of peripheral and cerebral vascular function between premenopausal, early and late postmenopausal females

What is the central question of this study? We sought to investigate whether peripheral and cerebrovascular function are impaired in early and late postmenopausal females compared with premenopausal females, while also accounting for nitric oxide and estradiol levels. What is the main finding and its importance? We observed no differences in peripheral vascular and cerebrovascular function between healthy and physically active premenopausal females and early and late postmenopausal females. Our findings contradict previous cross‐sectional observations of vascular and cerebrovascular dysfunction across menopause. Longitudinal studies assessing vascular and cerebrovascular outcomes across the menopausal transition are warranted.
Model of Preformed Hole-Pairs in c-Axis Transport in Cuprate Superconductors

Model of hole-pairs in electrical transport along ab plane in cuprate superconductors has already been proposed. It has been found to be in the shape of 3dx2–y2 orbital of an electron in an atom. This time, model of hole-pairs in transport along c-axis in cuprate superconductors is proposed. In ab-plane, hole-pairs are formed along CuO2 plane; one hole-pair covering 9 - 10 two dimensional CuO2 unit cells in 3dx2–y2 configuration. In the investigation of c-axis hole-pairs, cuprate superconductors have been sub-divided into three categories depending on the number of CuO2 planes/formula unit. There is a little different treatment for finding out the order parameter in each category. Coherence lengths along ab-planes are of the order of a few tens of Angstroms, whereas along c-axis, they are less than even their a-, b-lattice constants. In cuprates with 2 or 3 CuO2 planes, the order parameter is of 3dz2–x2 type in zx-plane with lobes along both the axes much constrained. For cuprates with a single CuO2 layer, the order parameter is of 3dx2–y2 type, but its dimensions are less than a-, b-lattice constants.