Coyleherndon5605

We present Posterior Temperature Optimized Bayesian Inverse Models (POTOBIM), an unsupervised Bayesian approach to inverse problems in medical imaging using mean-field variational inference with a fully tempered posterior. Bayesian methods exhibit useful properties for approaching inverse tasks, such as tomographic reconstruction or image denoising. A suitable prior distribution introduces regularization, which is needed to solve the ill-posed problem and reduces overfitting the data. In practice, however, this often results in a suboptimal posterior temperature, and the full potential of the Bayesian approach is not being exploited. In POTOBIM, we optimize both the parameters of the prior distribution and the posterior temperature with respect to reconstruction accuracy using Bayesian optimization with Gaussian process regression. Our method is extensively evaluated on four different inverse tasks on a variety of modalities with images from public data sets and we demonstrate that an optimized posterior temperature outperforms both non-Bayesian and Bayesian approaches without temperature optimization. The use of an optimized prior distribution and posterior temperature leads to improved accuracy and uncertainty estimation and we show that it is sufficient to find these hyperparameters per task domain. Well-tempered posteriors yield calibrated uncertainty, which increases the reliability in the predictions. Our source code is publicly available at github.com/Cardio-AI/mfvi-dip-mia.

With the increasing involvement of women in the workforce, the involvement of grandparents in infant care is a phenomenon that is climbing worldwide. Studies on intergenerational co-parenting are still in their infancy, and no consensus has been reached on the concept.

The aim here is to explore the antecedents, attributes, and consequences of intergenerational co-parenting and clarify the concept of intergenerational co-parenting specifically during the postpartum period.

The Rodgers' evolutionary framework (2000) for concept analysis was adopted to guide the process of developing, clarifying, and refining the concept of "intergenerational co-parenting."

A total of 14 original articles on intergenerational co-parenting covering the postpartum period were included. Six attributes were identified from the literature division of labor on infant care between parents and grandparents, generational boundaries, intergenerational transmission, reciprocal support between parents and grandparents in infant carcare. In addition, the components of division of labor, generational boundaries, mutual support between the generations on infant care, the commitment on parenting decision-making within two generations, and skills of intergenerational communication should be considered in intergenerational co-parenting interventions.

To describe the development of evidence-based recommendations on screening and managing women at risk for chorioamnionitis in resource-constrained healthcare settings.

A qualitative study, using data from an integrative literature review to develop the evidence-based recommendations was conducted. The NICE guideline development principles were followed to format the recommendations, which were reviewed by expert reviewers using the AGREE II tool.

Four main recommendations were developed, which were screening by clinical signs and symptoms; screening by causative factors of chorioamnionitis; screening of obstetric history; and prevention and management of chorioamnionitis. A screening tool and algorithm based on the recommendations were also developed.

Recommendations will assist midwives in identifying women at risk for chorioamnionitis and managing them before referral. The recommendations contribute to the quality care of women who are at risk for chorioamnionitis. The developed screening tool and achorioamnionitis.Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is an important regulator of the DNA damage response (DDR), especially in response to replication stress (RS). Tumor cells with ataxia-telangiectasia mutated (ATM) kinase loss of function or DDR defects that promote replicative stress are often more reliant on ATR for survival, highlighting ATR as a good antitumor target under the principle of synthetic lethality. Herein we report the discovery of a potent and highly selective ATR inhibitor, SKLB-197, which was obtained through structural optimization and structure-activity relationship (SAR) studies towards a hit compound (Cpd-1). SKLB-197 showed an IC50 value of 0.013 μM against ATR but very weak or no activity against other 402 protein kinases. It displayed potent antitumor activity against ATM-deficent tumors both in vitro and in vivo. In addition, this compound exhibited good pharmacokinetic properties. Overall, SKLB-197 could be a promising lead compound for drug discovery targeting ATR and deserves further in-depth studies.The NLRP3 inflammasome, which regulated a proinflammatory programmed cell death form termed pyroptosis, is involved in the pathological process of various human diseases, such as multiple sclerosis, type 2 diabetes, and gout. Thus, compounds inhibiting activation of the NLRP3 inflammasome can be promising treatments for these diseases. In this study, we conducted a phenotypic screening against NLRP3-dependent pyroptosis and discovered the hit compound 1, which showed moderate antipyroptotic activity. Chemistry efforts to improve potency of 1 resulted in a novel compound 59 (J114), which exhibited a half-maximal inhibitory concentration (IC50) of 0.077 ± 0.008 μM against cell pyroptosis. Interestingly, unlike all pyroptosis inhibitors currently reported, the activity of J114 showed significant differences in human- and mouse-derived cells. The IC50 of J114-mediated inhibition of IL-1β secretion by human THP-1 macrophages was 0.098 μM, which was nearly 150-fold and 500-fold more potent than that of J774A.1 (14.62 μM) and bone marrow-derived macrophages (BMDMs) (48.98 μM), respectively. Further studies showed that J114 displayed remarkable inhibitory activity against NLRP3- and AIM2-but not NLRC4-dependent activation of caspase-1 and the release of IL-1β in human THP-1 macrophages. Mechanistically, J114 disturbed the interaction of NLRP3 or AIM2 with the adaptor protein ASC and inhibited ASC oligomerization. Overall, our study identified a unique molecule that inhibits NLRP3 and AIM2 inflammasome activation and has species differences, which is worthy of further research to understand the differential regulation of the NLRP3 and AIM2 inflammasomes in humans and mice.

Speech and language cues are considered significant data sources that can reveal insights into one's behavior and well-being. The goal of this study is to evaluate how different machine learning (ML) classifiers trained both on the spoken word and acoustic features during live conversations between family caregivers and a therapist, correlate to anxiety and quality of life (QoL) as assessed by validated instruments.

The dataset comprised of 124 audio-recorded and professionally transcribed discussions between family caregivers of hospice patients and a therapist, of challenges they faced in their caregiving role, and standardized assessments of self-reported QoL and anxiety. We custom-built and trained an Automated Speech Recognition (ASR) system on older adult voices and created a logistic regression-based classifier that incorporated audio-based features. The classification process automated the QoL scoring and display of the score in real time, replacing hand-coding for self-reported assessments with aof accuracy. Examining the content, sound of the voice and context of the conversation provides insights into additional factors affecting anxiety and QoL that could be addressed in tailored therapy and the design of conversational agents serving as therapy chatbots.

We aimed to understand host factors that affect discriminatory performance of a transcriptomic signature of tuberculosis risk (RISK11).

HIV-negative adults aged 18-60 years were evaluated in a prospective study of RISK11 and surveilled for tuberculosis through 15 months. Generalised linear models and receiver-operating characteristic (ROC) regression were used to estimate effect of host factors on RISK11 score (%marginal effect) and on discriminatory performance for tuberculosis disease (area under the curve, AUC), respectively.

Among 2923 participants including 74 prevalent and 56 incident tuberculosis cases, percentage marginal effects on RISK11 score were increased among those with prevalent tuberculosis (+18·90%, 95%CI 12·66-25·13), night sweats (+14·65%, 95%CI 5·39-23·91), incident tuberculosis (+7·29%, 95%CI 1·46-13·11), flu-like symptoms (+5·13%, 95%CI 1·58-8·68), and smoking history (+2·41%, 95%CI 0·89-3·93) than those without; and reduced in males (-6·68%, 95%CI -8·31- -5·04) and with every unit increase in BMI (-0·13%, 95%CI -0·25- -0·01). BIRB 796 inhibitor Adjustment for host factors affecting controls did not change RISK11 discriminatory performance. Cough was associated with 72·55% higher RISK11 score in prevalent tuberculosis cases. Stratification by cough improved diagnostic performance from AUC=0·74 (95%CI 0·67-0·82) overall, to 0·97 (95%CI 0·90-1·00, p<0·001) in cough-positive participants. Combining host factors with RISK11 improved prognostic performance, compared to RISK11 alone, (AUC=0·76, 95%CI 0·69-0·83 versus 0·56, 95%CI 0·46-0·68, p<0·001) over a 15-month predictive horizon.

Several host factors affected RISK11 score, but only adjustment for cough affected diagnostic performance. Combining host factors with RISK11 should be considered to improve prognostic performance.

Bill and Melinda Gates Foundation, South African Medical Research Council.

Bill and Melinda Gates Foundation, South African Medical Research Council.

An understanding of the correlation between maternal immunity and congenital cytomegalovirus (CMV) infection is critical for informing the design and evaluation of an effective maternal vaccine. This study aimed to quantitatively measure the protective effect of pre-existing maternal immunity against congenital CMV (cCMV) infection.

A mother-child cohort study was conducted in three maternal and child health hospitals in China from 2015 to 2018. Pregnant women were consecutively enrolled, and anti-CMV pp150 IgG concentration at early, middle and late gestational ages were evaluated. Their newborns were screened for cCMV infection by CMV-DNA testing of saliva and urine.

In total, 6729 pregnant women were enrolled, and 6602 of them (98·11%) were positive for CMV IgG at their early gestational age visit (median time 13 gestational weeks (GW); time range 6-25 GW). In total, 6228 live newborns were born to seropositive mothers, and 48 (0·77%) of these infants were diagnosed with cCMV infection. The geometric of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.

National Natural Science Foundation of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.