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Latent profile analysis of girls' morning cortisolC-reactive protein ratio, positive and negative affect levels, and attentional set-shifting ability revealed four profiles. Relative to Normative (66.6%), girls exhibiting a Pro-inflammatory Affective Disturbance (13.1%), Severe Affective Disturbance (10.1%), or Hypercortisol Affective Neurocognitive Disturbance (n = 24, 10.1%) profile reported exposure to a greater number of maltreatment subtypes while growing up. Girls exhibiting these dysregulated profiles were also more likely (relative to Normative) to report current depressive symptoms (all three profiles) and PASI (only Pro-inflammatory Affective Disturbance and Hypercortisol Affective Neurocognitive Disturbance). Of note, girls' cognitive reappraisal utilization moderated profile membership-depression linkages (depressive symptoms, but not PASI). A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.Paroxetine, a selective serotonin reuptake inhibitor (SSRI), is prescribed to treat psychiatric disorders, although an off-label SSRI use is also for functional gastrointestinal disorders. The mutual correlation between serotonin and peripheral sex steroids has been reported, however little attention to sex steroids synthesized by gut, has been given so far. Indeed, whether SSRIs, may also influence the gut steroid production, immediately after treatment and/or after suspension, is still unclear. The finding that gut possesses steroidogenic capability is of particular relevance, also for the existence of the gut-microbiota-brain axis, where gut microbiota represents a key orchestrator. On this basis, adult male rats were treated daily for two weeks with paroxetine or vehicle and, 24 h after treatment and at 1 month of withdrawal, steroid environment and gut microbiota were evaluated. Results obtained reveal that paroxetine significantly affects steroid levels, only in the colon but not in plasma. In particular, steroid modifications observed immediately after treatment are not overlap with those detected at withdrawal. Additionally, paroxetine treatment and its withdrawal impact gut microbiota populations differently. Altogether, these results suggest a biphasic effect of the drug treatment in the gut both on steroidogenesis and microbiota.

The use of whole slide imaging (WSI) for frozen section (FS) diagnosis is helpful, particularly in the context of pathologist shortages. However, there is minimal data on such usage in resource-limited settings. This study aims to validate the use of WSI for FS diagnosis of lymph node metastasis using a low-cost virtual microscope scanner with consumer-grade laptops at a tertiary care hospital in Thailand.

FS slides were retrieved for which the clinical query was to evaluate lymph node metastasis. They were digitized by a virtual microscope scanner (MoticEasyScan, Hong Kong) using up to 40× optical magnification. Three observers with different pathology experience levels diagnosed each slide, reviewing glass slides (GS) followed by digital slides (DS) after two weeks of a wash out period. WSI and GS diagnoses were compared. The time used for scanning and diagnosis of each slide was recorded.

295 FS slides were retrieved and digitized. The first-time successful scanning rate was 93.6 %. The mean scanning time was 2 min per slide. Both intraobserver agreement and interobserver agreement of WSI and GS diagnoses were high (Cohen's K; kappa value >0.84). The time used for DS diagnosis decreased as the observer's experience with WSI increased.

Despite varying pathological experiences, observers using WSI provided accurate FS diagnoses of lymph node metastasis. The time required for DS diagnoses decreased with additional observer's experience with WSI. Therefore, a WSI system containing low-cost scanners and consumer-grade laptops could be used for FS services in hospital laboratories lacking pathologists.

Despite varying pathological experiences, observers using WSI provided accurate FS diagnoses of lymph node metastasis. The time required for DS diagnoses decreased with additional observer's experience with WSI. Therefore, a WSI system containing low-cost scanners and consumer-grade laptops could be used for FS services in hospital laboratories lacking pathologists.Redundant manipulators could be efficient tools in industrial production as a result of their dexterity. However, existing kinematic control methods for redundant manipulators have two main disadvantages. On one hand, model uncertainties or unknown kinematic parameters may degrade the performance of existing model-based control methods subject to joint limits. On the other hand, existing model-free control methods ignore the existence of joint limits although they do not need to know kinematic models of redundant manipulators. In this paper, a quadratic programming (QP) scheme is elaborated to achieve the primary tracking control task of redundant manipulators as well as joint limits avoidance task. Besides, a gradient neurodynamics (GND) model is utilized to estimate the kinematics of redundant manipulators. Then, a primal dual neural network, which is employed to solve the QP problem, and the GND model are integrated towards developing a model-free control method constrained by joint angle and velocity limits for redundant manipulators. The visual sensory feedback is fed to the two neural networks. selleck chemicals The efficacy of the proposed control method is demonstrated by extensive simulations and experiments, and the merits of the proposed method are also substantiated by comparisons.Despite the successful use of Gaussian-binary restricted Boltzmann machines (GB-RBMs) and Gaussian-binary deep belief networks (GB-DBNs), little is known about their theoretical approximation capabilities to represent distributions of continuous random variables. In this paper, we address the expressive properties of GB-RBMs and GB-DBNs, contributing theoretical insights to the optimal number of hidden variables. We first treat the GB-RBM's unnormalized log-likelihood as a sum of a special two-layer feedforward neural network and a negative quadratic term. Then, a series of simulation results are established, which can be used to relate GB-RBMs to general two-layer feedforward neural networks whose expressive properties are much better understood. On this basis, we show that a two-layer ReLU network with all weights in the second layer being 1, along with a negative quadratic term, can approximate all continuous functions. In addition, we provide qualified lower bounds for the number of hidden variables of GB-RBMs required to approximate distributions whose log-likelihood are given by some classes of smooth functions. Moreover, we further study the universal approximation of GB-DBNs with two hidden layers by providing a sufficient number of hidden variables O(ɛ-2) that are guaranteed to approximate any given strictly positive continuous distribution within a given error ɛ. Finally, numerical experiments are carried out to verify some of the proposed theoretical results.

Evidence has shown that frailty is associated with the risk of falls in older people. However, the components of frailty that have the highest association with fall events are largely unknown.

This study analyzed panel data from the Korean Longitudinal Study of Aging. We used the Korean Frailty Instrument, which includes domains for social isolation, exhaustion and weakness estimated by grip strength, to assess frailty. Fall event data were collected during follow-up visits.

A total of 3122 community-dwelling adults aged 65 years or older were included at baseline in 2006 and were followed up every 2 years until 2018. The participants with frailty had a higher risk of falls than those without frailty (OR=1.31, 95% CI=1.11-1.54, P=0.001; fully adjusted model). We found that three components of frailty, namely, social isolation, exhaustion, and weakness, were independently and significantly related to fall events in the unadjusted model. In the fully adjusted model, social isolation and exhaustion were significantly associated with fall events (OR=1.38, 95% CI=1.18-1.61, P < 0.001 and OR=1.28, 95% CI=1.10-1.51, P=0.006, respectively), and there was no significant association between weakness and the risk of falls (OR=1.11, 95% CI=0.91-1.34, P=0.307).

Frailty was associated with more fall events in Korean older adults. Social isolation and exhaustion but not weakness were significantly associated with fall events. Our study suggests that interventions should be tailored to older adults with social and psychological frailty.

Frailty was associated with more fall events in Korean older adults. Social isolation and exhaustion but not weakness were significantly associated with fall events. Our study suggests that interventions should be tailored to older adults with social and psychological frailty.Human carboxylesterase 2 (hCES2) converts anticancer prodrugs, such as irinotecan, into their active metabolites via phase I drug metabolism. Owing to interindividual variability, hCES2 serves as a predictive marker of patient response to hCES2-activated prodrug-based therapy, whereby a low intratumoral hCES2 activity leads to therapeutic resistance. Despite the ability to identify nonresponders, effective treatments for resistant patients are needed. Clinically approved photodynamic therapy is an attractive alternative for irinotecan-resistant patients. Here, we describe the application of our hCES2-selective small-molecule ratiometric fluorescent chemosensor, Benz-AP, as a single theranostic agent given its discovered functionality as a photosensitizer. Benz-AP produces singlet oxygen and induces photocytotoxicity in cancer cells in a strong negative correlation with hCES2 activity. Two-photon excitation of Benz-AP produces fluorescence, singlet oxygen, and photocytotoxicity in tumor spheroids. Overall, Benz-AP serves as a novel theranostic agent with selective photocytotoxicity in hCES2-prodrug resistant cancer cells, making Benz-AP a promising agent for in vivo applications.Bacille Calmette-Guerin (BCG) is the only approved vaccine against tuberculosis but the subcutaneous route does not provide for the elimination of Mycobacterium tuberculosis (Mtb), thus highlighting the need for investigating other routes of administration. We used a unique set of 60 peptide pools with unprecedented coverage of the bacterium that had previously been used to study T cell responses in subjects latently infected with Mtb. We showed that intravenous BCG vaccination of C57BL/6 mice elicited a more robust IFN-γ response from splenocytes than the subcutaneous route, with the highest responses driven by the Ag85A/B and PE/PPE family epitopes, followed by TB10.4 and Esx-1. We then compared the spectrum of antigen recognition in BCG-naïve H37Rv-challenged and BCG-vaccinated H37Rv-challenged mice. Peptides belonging to TB10.4, ESAT-6, CFP-10, Ag85A/Ag85B, PE/PPE and Esx families up-regulated IFN-γ production in the lungs of BCG-naïve H37Rv-challenged mice but the response was much lower in the BCG-vaccinated group. Historically, a limited number of Mtb antigens have been used to study T cell responses in TB. The goal of using this 60-peptide assay was to define T cell responses in TB down to the epitope level. We envision that the use of broad antigen panels such as ours in conjunction with studies of bacterial load reduction will help delineate the protective efficacy of 'groups' of antigens.