Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous variable selection and estimation for joint models of longitudinal and failure time data with interval censoring

This paper discusses variable selection in the context of joint analysis of longitudinal data and failure time data. A large literature has been developed for either variable selection or the joint analysis but there exists only limited literature for variable selection in the context of the joint analysis when failure time data are right censored. Corresponding to this, we will consider the situation where instead of right‐censored data, one observes interval‐censored failure time data, a more general and commonly occurring form of failure time data. For the problem, a class of penalized likelihood‐based procedures will be developed for simultaneous variable selection and estimation of relevant covariate effects for both longitudinal and failure time variables of interest. In particular, a Monte Carlo EM (MCEM) algorithm is presented for the implementation of the proposed approach. The proposed method allows for the number of covariates to be diverging with the sample size and is shown to have the oracle property. An extensive simulation study is conducted to assess the finite sample performance of the proposed approach and indicates that it works well in practical situations. An application is also provided.
Normative reference values for estimated cardiorespiratory fitness in apparently healthy British men and women

Objectives To develop normative reference standards for estimated cardiorespiratory fitness (eCRF) measured from treadmill-based incremental exercise testing in ~12 000 British men and women. Methods Cross-sectional study using retrospectively collected eCRF data from five preventative health screening clinics in the United Kingdom. Reference centiles were developed using a parametric approach by fitting fractional polynomials. We selected the ‘best’ powers by considering both the smallest deviance, and clinical knowledge from the following set of a priori decided powers (-2,-1,-0.5, 0, 0.5,1,2,3). A series of fractional polynomials (FPs) were investigated with three-parameters (median, standard deviation and skewness). The following reference centiles were plotted (3, 5, 10, 25, 50, 75, 90, 95, 97). Results We included 9 204 males (median [25th,75th centiles] age 48 [44, 53] years; BMI 27 {25, 29] kg∙m-2; peak VO2 36.9 [30.5, 44.7] ml∙kg-1∙min-1) and 2 687 females (age 48, [41, 51] years; BMI 24 {22, 27] kg∙m-2; peak VO2 36.5 [30.1, 44.8] ml∙kg-1∙min-1) in our analysis to develop the normative values. Conclusion Reference values and nomograms for eCRF were derived from a relatively large cohort of preventative health care screening examinations of apparently healthy British men and women. Age- and sex-specific eCRF percentiles were similar to data from international cohort studies. The adoption of submaximal exercise testing protocols reduces individual risk when exercise history is unknown and testing is conducted in a community-based setting. Our findings can be used by health professionals to help guide clinical decision making.
Regional differences in zygapophysial joint cavities: A histological study of human fetuses

Human zygapophysial joints (ZJ) have regional differences in shape and orientation during prenatal growth. However, there is limited knowledge of the synovial recess during fetal development. We examined sagittal and horizontal histological sections of the vertebral columns of 30 human fetuses at gestational ages of 8–37 weeks. Fetuses of all gestational ages had subaxial cervical articular processes that were thicker than in the thoracolumbar regions, and as large as the corresponding vertebral bodies. A small or large synovial recess extending beyond the articular cartilage was evident at most regions. The cervical ZJ had large or deep recesses that extended inferiorly in midterm fetuses and posteromedially along the vertebral pedicle and lamina in near‐term fetuses. Likewise, the thoracic ZJ had small recesses that extended superiorly in midterm fetuses and medially in near‐term fetuses. The lumbar recesses extended laterally beyond the medially shifted articular cartilage of the upper adjacent vertebrae in near‐term fetuses and the lumbar articular surface was smallest in the three regions at all stages. At any region, a deep recess appeared before an area expansion of the ZJ cartilage. A drastic change in direction and size of the prenatal recess seemed to occur depending on a possible minute dislocation of the ZJ. In particular, a deep posteromedial recess of the cervical ZJ, which extended far beyond the articular cartilage, might be necessary to maintain high flexibility suitable for the strong flexion posture in utero.
What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate and associated risk factors

Introduction Current SARS-CoV-2 containment measures rely on controlling viral transmission. Effective prioritization can be determined by understanding SARS-CoV-2 transmission dynamics. We conducted a systematic review and meta-analyses of the secondary attack rate (SAR) in household and healthcare settings. We also examined whether household transmission differed by symptom status of index case, adult and children, and relationship to index case. Methods We searched PubMed, medRxiv, and bioRxiv databases between January 1 and July 25, 2020. High-quality studies presenting original data for calculating point estimates and 95% confidence intervals (CI) were included. Random effects models were constructed to pool SAR in household and healthcare settings. Publication bias was assessed by funnel plots and Egger’s meta-regression test. Results 43 studies met the inclusion criteria for household SAR, 18 for healthcare SAR, and 17 for other settings. The pooled household SAR was 18.1% (95% CI: 15.7%, 20.6%), with significant heterogeneity across studies ranging from 3.9% to 54.9%. SAR of symptomatic index cases was higher than asymptomatic cases (RR: 3.23; 95% CI: 1.46, 7.14). Adults showed higher susceptibility to infection than children (RR: 1.71; 95% CI: 1.35, 2.17). Spouses of index cases were more likely to be infected compared to other household contacts (RR: 2.39; 95% CI: 1.79, 3.19). In healthcare settings, SAR was estimated at 0.7% (95% CI: 0.4%, 1.0%). Discussion While aggressive contact tracing strategies may be appropriate early in an outbreak, as it progresses, measures should transition to account for setting-specific transmission risk. Quarantine may need to cover entire communities while tracing shifts to identifying transmission hotspots and vulnerable populations. Where possible, confirmed cases should be isolated away from the household.
Erector spinae plane block for postoperative pain and recovery in hepatectomy

Abstract Background: The randomized controlled study aimed to examine the efficacy of preoperative ultrasound-guided erector spinae plane (ESP) block combined with ropivacaine in patients undergoing hepatectomy. Methods: A total of 60 patients were randomized to ESP block group receiving ropivacaine (Group A) and control group (Group B), n = 30 per group. Visual analog scale (VAS) was recorded in both the groups during rest and movement at the various time intervals. Both the groups were also compared for time to initial anal exhaust, analgesic usage, early postoperative complications and side-effects, walk distance after the operation, time to out-of-bed activity, and duration of hospital stay. Results: No significant differences were observed in the demographic characteristics. For group A, when compared to group B, VAS scores during rest and movement within post-operative 24 hours were decreased, the time of first anus exhaust and ambulation were earlier, analgesic consumption and the incidence of postoperative nausea, vomiting and headache was reduced, the duration of hospital stay were shorter with longer walk distance. Conclusion ESP block combined with ropivacaine treatment effectively reduced early postoperative pain and improved recovery after hepatectomy.
17β-Estradiol Treatment Protects Lungs Against Brain Death Effects in Female Rat Donor.

BACKGROUND Brain death (BD) affects the viability of lungs for transplantation. A correlation exists between high lung inflammation after BD and the decrease in female sex hormones, especially estradiol. Therefore, we investigated the effects of 17β-estradiol (E2) treatment on the lungs of female brain dead rats. METHODS Female Wistar rats were divided into 4 groups: BD (submitted to BD for 6 h), sham (false-operated), E2-T0 (treated with E2 immediately after BD; 50 μg/ml, 2 ml/h), and E2-T3 (treated with E2 after 3 h of BD; 50 μg/ml, 2 ml/h). Lung edema, hemorrhage, and leukocyte infiltration were analyzed. Adhesion molecules were evaluated and analysis of NO synthase gene and protein expression was performed using RT-PCR and immunohistochemistry, respectively. Release of chemokines and matrix degradation in the lungs were analyzed. RESULTS BD increased leukocyte infiltration, as shown by intravital microscopy (P=0.017), bronchoalveolar lavage cell count (P=0.016), the release of inflammatory mediators (P=0.02), and expression of adhesion molecules. BD also increased microvascular permeability and the expression and activity of MMP-9 in the lungs. E2 treatment reduced leukocyte infiltration, especially in the E2-T3 group, release of inflammatory mediators, adhesion molecules, and MMP activity in the lungs. CONCLUSIONS E2 treatment was successful in controlling the lung inflammatory response in females submitted to BD. Our results suggest that E2 directly decreases the release of chemokines, restraining cell traffic into the lungs. Thus, E2 has a therapeutic potential, and its role in improving donor lung quality should be explored further.
Trends in COVID-19 Incidence After Implementation of Mitigation Measures — Arizona, January 22–August 7, 2020

Mitigating the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), requires individual, community, and state public health actions to prevent person-to-person transmission. Community mitigation measures can help slow the spread of COVID-19; these measures include wearing masks, social distancing, reducing the number and size of large gatherings, pausing operation of businesses where maintaining social distancing is challenging, working from or staying at home, and implementing certain workplace and educational institution controls (1-4). The Arizona Department of Health Services' (ADHS) recommendations for mitigating exposure to SARS-CoV-2 were informed by continual monitoring of patient demographics, SARS-CoV-2 community spread, and the pandemic's impacts on hospitals. To assess the effect of mitigation strategies in Arizona, the numbers of daily COVID-19 cases and 7-day moving averages during January 22-August 7, 2020, relative to implementation of enhanced community mitigation measures, were examined. The average number of daily cases increased approximately 151%, from 808 on June 1, 2020 to 2,026 on June 15, 2020 (after stay-at-home order lifted), necessitating increased preventive measures. On June 17, local officials began implementing and enforcing mask wearing (via county and city mandates),* affecting approximately 85% of the state population. Statewide mitigation measures included limitation of public events; closures of bars, gyms, movie theaters, and water parks; reduced restaurant dine-in capacity; and voluntary resident action to stay at home and wear masks (when and where not mandated). The number of COVID-19 cases in Arizona peaked during June 29-July 2, stabilized during July 3-July 12, and further declined by approximately 75% during July 13-August 7. Widespread implementation and enforcement of sustained community mitigation measures informed by state and local officials' continual data monitoring and collaboration can help prevent transmission of SARS-CoV-2 and decrease the numbers of COVID-19 cases.
Flexural properties, bond ability, and crystallographic phase of highly translucent multi-layered zirconia

This study investigated the mechanical properties, bond ability, and crystallographic forms of different sites in a highly translucent, multi-layered zirconia disk. Flexural properties, bond ability to resin cement, and phase composition were investigated at three sites of a highly translucent, multi-layered zirconia disk: incisal, middle, and cervical. Flexural strength (FS) and flexural modulus (FM) were measured with static three-point flexural test. Shear bond strength (SB) to resin cement was measured after 24 h storage (37°C). Phase composition under mechanical stress was analyzed using X-ray diffraction. Without air abrasion, FS at the incisal site yielded the lowest value and was significantly lower than the middle and cervical sites. Air abrasion lowered the FS of each site. FM at the incisal site without air abrasion showed the significantly lowest value, and air abrasion increased its FM value. At the middle and cervical sites, their FM values were higher than the incisal site but were not significantly affected by air abrasion. SB value did not show significant differences among the sites. After sintering, cubic zirconia was detected at each site. Rhombohedral phase transformation occurred after mirror polishing. In highly translucent, multi-layered zirconia which was mainly composed of cubic zirconia, rhombohedral phase transformation occurred under mechanical stress and resulted in weakened mechanical properties.
FOXP3 mRNA Profile Prognostic of Acute T Cell–mediated Rejection and Human Kidney Allograft Survival

Supplemental Digital Content is available in the text. Background. T cell–mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes are nonresponsive to therapy, and molecular mechanisms for the nonresponsiveness are unknown. Our single-center study identified that urinary cell FOXP3 mRNA abundance predicts TCMR reversibility and allograft survival. Methods. We developed PCR assays and measured absolute copy numbers of transcripts for FOXP3, CD25, CD3E, perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in the multicenter Clinical Trials in Organ Transplantation-04. In this replication study, we investigated the association between mRNA profile and TCMR diagnosis, TCMR reversibility, and allograft survival. Results. 18S rRNA normalized levels of mRNA for FOXP3 (P = 0.01, Kruskal-Wallis test), CD25 (P = 0.01), CD3E (P < 0.0001), and perforin (P < 0.0001) were diagnostic of TCMR, but only FOXP3 mRNA level predicted TCMR reversibility (ROC AUC = 0.764; 95% confidence interval, 0.611-0.917; P = 0.008). Multivariable logistic regression analyses showed that urinary cell FOXP3 mRNA level predicted reversal, independent of clinical variables. A composite model of clinical variables and FOXP3 mRNA (AUC = 0.889; 95% CI, 0.781-0.997; P < 0.001) outperformed FOXP3 mRNA or clinical variables in predicting TCMR reversibility (P = 0.01, likelihood ratio test). Multivariable Cox proportional hazards regression analyses showed that FOXP3 mRNA level predicts kidney allograft survival (P = 0.047) but not after controlling for TCMR reversal (P = 0.477). Conclusions. Urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts TCMR reversibility, and is prognostic of kidney allograft survival via a mechanism involving TCMR reversal.
In silico evidence supports a role for DNA methylation in Sirt1-mediated effects of dietary restriction

Dietary restriction (DR) remains one of the most robust dietary interventions proved effective to increase lifespan across evolutionarily distinct species, from yeast to rodents. The NAD-dependent (class III) histone deacetylase Sirt1 in mammals, and its orthologue in other species, may be pivotal in mediating the effect of DR to increase lifespan. Ageing is associated with changes in genome methylation (e.g.), which may be causative in the ageing process. Such observations, in view of the activity of Sirt1 at the level of the epigenome, form the basis for our hypothesis that epigenetic effects of Sirt1 activity mediate some of the beneficial effects of DR that contribute to lifespan extension. Our approach to testing this hypothesis was to determine the overlap between genes that bind Sirt1, those regulated at the mRNA level in response to DR and those that show an age-related change in methylation status, predicted on the principle that overlaps greater than would be expected by chance would support our hypothesis. By representing all genes using ENSEMBL identifiers, we identified overlaps between a list of 418 genes identified as interacting physically with the histone deacetylase Sirt1, a list of 2954 genes found to respond to DR, compiled from 11 published studies, and a list of 1040 genes whose DNA methylation status changed in mouse small intestine in association with ageing. All overlaps were found to be greater than would be expected by chance using the principle of hypergeometric distribution, as shown in Table 1. The promoter regions of 80 of the 91 genes that responded to DR and also bound Sirt1 (i.e. 88%) were found to include CpG islands (defined as having a GC content of greater that 50% and CpG observed/expected ratio of greater than 0.6), representing sites of potential differential methylation in ageing tissues; this proportion is also greater than would be expected by chance (representation factor = 1.47, P = 3.395 · 10 ), based on the assumption that 60% of mouse genes have associated CpG islands.
A Transport-resistance Model of Forest Growth and Partitioning

The transport-resistance approach to dry-matter partitioning is used to construct a model of forest growth. The model is at the stand level for a monoculture of identical trees of the same age. There are five major organ compartments in the model : foliage, branches, stem, coarse roots, and fine roots and mycorrhizas. The matter in each compartment is further subdivided into meristem, structure, carbon substrate, and nitrogen substrate. The model is driven by daily radiation including day length, ambient CO 2 concentration, and daily means of air and soil temperature (.)
Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study

Abstract Background Depression and cardiovascular disease (CVD) are associated with each other but their relationship remains unclear. We aim to determine whether genetic predisposition to depression are causally linked to CVD [including coronary artery disease (CAD), myocardial infarction (MI), stroke and atrial fibrillation (AF)]. Methods Using summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis: n = 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis: n = 322 580), CAD (n = 184 305), MI (n = 171 875), stroke (n = 446 696) and AF (n = 1 030 836), genetic correlation was tested between two depression phenotypes and CVD [MI, stroke and AF (not CAD as its correlation was previously confirmed)]. Causality was inferred between correlated traits by Mendelian Randomization analyses. Results Both depression phenotypes were genetically correlated with MI (depression: rG = 0.169; p = 9.03 × 10−9; broad depression: rG = 0.123; p = 1 × 10−4) and AF (depression: rG = 0.112; p = 7.80 × 10−6; broad depression: rG = 0.126; p = 3.62 × 10−6). Genetically doubling the odds of depression was causally associated with increased risk of CAD (OR = 1.099; 95% CI 1.031–1.170; p = 0.004) and MI (OR = 1.146; 95% CI 1.070–1.228; p = 1.05 × 10−4). Adjustment for blood lipid levels/smoking status attenuated the causality between depression and CAD/MI. Null causal association was observed for CVD on depression. A similar pattern of results was observed in the secondary analysis for broad depression. Conclusions Genetic predisposition to depression may have positive causal roles on CAD/MI. Genetic susceptibility to self-awareness of mood problems may be a strong causal risk factor of CAD/MI. Blood lipid levels and smoking may potentially mediate the causal pathway. Prevention and early diagnosis of depression are important in the management of CAD/MI.
Transitioning to a new era: Future directions for staff development during COVID‐19

The COVID‐19 pandemic created an urgent need for staff development. However, COVID‐19 has created many challenges, including the inability to meet in‐person, travel restrictions to conferences, overwhelming clinical demands on already overextended faculty members and the increased need to focus on personal health and safety. Although current challenges were immediately met with solutions borne out of an emergency, questions remain on how to identify and sustain best practices and further evolve staff development beyond the immediate crisis. Reviewing the Medical Adaptations series revealed several lessons. Several authors used cognitive apprenticeship to provide scaffolding upon which learners can build skills, knowledge and attitudes. Additionally, moderators were recommended during live educational sessions in order to manage the chat box and engage the audience. Comprehensive IT support was key. A post‐session debrief helped deepen understanding and provided a space for peer support and community building. Building a repository for educational materials was recommended. Although we made significant gains in the ability to offer staff development, we must consider potential and unintended consequences and explore how we can use transformative learning theory to capitalize on what we have gained. Utilizing technology can potentially increase access to online learning; however, when not implemented carefully, it can magnify inequities. While providing IT support can serve to mitigate some inequities borne by socioeconomic and generational differences, additional strategies should be implemented to account for English as a second‐language learners; those with disabilities who do not have access to adaptive technology; and other marginalized groups who may already feel vulnerable to presenting arguments in oppositions of authority or the majority. Crafting online education experiences to allow for small group, peer‐to‐peer and social interactions is vital to continued professional and identity development. Now that the urgency has lessened, taking time to ensure what is being offered follows best practices in developing and disseminating quality online education is paramount for broad acceptance.
A survey of the experience of living with dementia in a dementia-friendly community

Dementia-friendly communities (DFCs) are one way in which people living with dementia can be supported to be active, engaged and valued citizens. Quantitative evaluations of the experiences of those with dementia living within these communities are scarce. This article reports findings from a survey of people living with dementia on their experience of living in a DFC. Two-hundred and forty people living with dementia completed a cross-sectional survey in six DFCs across England. Around half of respondents reported they were aware they were living in a DFC. Being aware of living in a DFC was associated with taking part in leisure activities (p = 0.042), community centre attendance (p = 0.009), being involved in organised activities or groups (p < 0.001), feeling understood (p = 0.008), and feeling valued for their own contributions to the community (p = 0.002). This study illustrates the contribution that surveys can make in facilitating the expression of views and experiences of people living with dementia. Awareness of living within a DFC is associated with greater involvement in, and belonging to, the wider community.