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Despite the controversy, there seems to be little evidence to support that anesthesia itself or other surgical and patient factors can cause or accelerate AD.Objective.The red bone marrow (RBM) and bone endosteum (BE), which are required for effective dose calculation, are macroscopically modeled in the reference phantoms of the international commission on radiological protection (ICRP) due to their microscopic and complex histology. In the present study, the detailed bone models were developed to simplify the dose calculation process for skeletal dosimetry.Approach.The detailed bone models were developed based on the bone models developed at the University of Florida. A new method was used to update the definition of BE region by storing the BE location indices using virtual sub-voxels. The detailed bone models were then installed in the spongiosa regions of the ICRP mesh-type reference computational phantoms (MRCPs) via the parallel geometry feature of the Geant4 code.Main results.Comparing the results between the detailed-bone-installed MRCPs and the original MRCPs with the absorbed dose to spongiosa and fluence-to-dose response function (DRF)-based methods, the DRF-based method showed much smaller but still significant differences. Compared with the values given in ICRPPublications116 and 133, the differences were very large (i.e. several orders of magnitudes), due mainly to the anatomical improvement of the skeletal system in the MRCPs; that is, spongiosa and medullary cavity are fully enclosed by cortical bone in the MRCPs but not in the ICRP-110 phantoms.Significance.The detailed bone models enable the direct calculation of the absorbed doses to the RBM and BE, simplifying the dose calculation process and potentially improving the consistency and accuracy of skeletal dosimetry.

Specifying peri- and postnatal factors in children born very preterm (VPT) that affect later outcome helps to improve long-term treatment.

To enhance the predictability of 5-year cognitive outcome by perinatal, 2-year developmental and socio-economic data.

92 VPT infants, born 2007-2009, gestational age<32 weeks and/or birthweight of 1500 g, were assessed longitudinally including basic neonatal, socio-economic (SES), 2-year Mental Developmental Index (MDI, Bayley Scales II), 5-year Mental Processing Composite (MPC, Kaufman-Assessment Battery for Children), and Language Screening for Preschoolers data. 5-year infants born VPT were compared to 34 term controls.

The IQ of 5-year infants born VPT was 10 points lower than that of term controls and influenced independently by preterm birth and SES. MDI, SES, birth weight and birth complications explained 48% of the variance of the MPC. The MDI proved highly predictive (r=0.6, R2=36%) for MPC but tended to underestimate the cognitive outcome. A total of 61% of the 2-year infants born VPT were already correctly classified (specificity of .93, sensitivity of .54). CHAID decision tree technique identified SES as decisive for the outcome for infants born VPT with medium MDI results (76-91) They benefit from effects associated to a higher SES, while those with a poor MDI outcome and a birth weight≤890 g do not.

Developmental follow-up of preterm children enhances the quality of prognosis and later outcome when differentially considering perinatal risks and SES.

Developmental follow-up of preterm children enhances the quality of prognosis and later outcome when differentially considering perinatal risks and SES.

There is a common belief that seniority and gender are associated with clinicians' perceptions of the value of electronic health record (EHR) technology and the propensity for burnout. Insufficient evidence exists on the relationship between these variables.

The aim of this study was to investigate how seniority/years of practice, gender, and screened burnout status are associated with opinions of EHR use on quality, cost, and efficiency of care.

We surveyed ambulatory primary care and subspecialty clinicians at three different institutions to screen for burnout status and to measure their opinions (positive, none, negative, don't know) on how EHR technology has impacted three important attributes of health care quality, cost, and efficiency of care. We used chi-square tests to analyze association between years of practice (≤10 years or 11+ years), gender, and screened burnout status and the reported attributes. We used a Bonferroni-corrected

 = 0.0167 for significance to protect against type I error eived value of EHR technologies, while years of practice and gender are not. This contests the popular notion that junior clinicians view EHR technology more favorably than their more senior counterparts. find more Hence, burnout status may be an important factor associated with the overall value clinicians ascribe to EHR technologies.Preeclampsia (PE) may pose significant adverse effects on pregnant women. Dysregulation of angiogenesis, trophoblast invasion, and proliferation are known to be associated with PE development and progression. Fms related tyrosine kinase 1 (FLT1), an anti-angiogenic factor, is consistently upregulated in PE patients. Recent papers highlight that aberrant miR-30a-3p expression contributes to PE development. More effects are needed to assess the biological function of placental miR-30a-3p in PE. The soluble FLT1 (sFLT1) and FLT1 levels were tested by ELISA assay and Western blotting assay. mRNA levels were measured by RT-qPCR assay. Colony formation and MTT assays were applied to assess the effect of miR-30a-3p on trophoblast cell proliferation. The serum sFLT1 and placental FLT1 levels were substantially high in patients with PE. Using miRNA microarray assay, we identified miR-30a-3p upregulation in PE patients' placenta tissues. We further confirmed that miR-30a-3p binds to the 3'-UTR of FLT1 gene and positively regulate its expression. Forcing miR-30a-3p expression inhibited trophoblast cell proliferation and vice versa. In conclusion, persistent high levels of FLT1 and miR-30a-3p may pose adverse effects on angiogenesis and trophoblast proliferation in placenta of PE patients. Therefore, targeting FLT1 and miR-30a-3p may serve as ideal strategies for managing patients with PE.How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8+ T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8+ T cells, with lactate directly fueling the TCA cycle. In fact, CD8+ T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro, with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8+ T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo. Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8+ effector T cells.Small cell lung cancer (SCLC) tumors comprise heterogeneous mixtures of cell states, categorized into neuroendocrine (NE) and non-neuroendocrine (non-NE) transcriptional subtypes. NE to non-NE state transitions, fueled by plasticity, likely underlie adaptability to treatment and dismal survival rates. Here, we apply an archetypal analysis to model plasticity by recasting SCLC phenotypic heterogeneity through multi-task evolutionary theory. Cell line and tumor transcriptomics data fit well in a five-dimensional convex polytope whose vertices optimize tasks reminiscent of pulmonary NE cells, the SCLC normal counterparts. These tasks, supported by knowledge and experimental data, include proliferation, slithering, metabolism, secretion, and injury repair, reflecting cancer hallmarks. SCLC subtypes, either at the population or single-cell level, can be positioned in archetypal space by bulk or single-cell transcriptomics, respectively, and characterized as task specialists or multi-task generalists by the distance from archetype vertex signatures. In the archetype space, modeling single-cell plasticity as a Markovian process along an underlying state manifold indicates that task trade-offs, in response to microenvironmental perturbations or treatment, may drive cell plasticity. Stifling phenotypic transitions and plasticity may provide new targets for much-needed translational advances in SCLC. A record of this paper's Transparent Peer Review process is included in the supplemental information.

The purpose of this study was to build a risk prediction model to identify trauma patients at the time of injury who are at high risk for post-traumatic stress disorder (PTSD) 1year later.

Patients 18+ with operative orthopedic trauma injuries were enrolled in prospective social determinants of health cohort. Data were collected through initial surveys, medical records at time of injury, and 1-year follow-up phone screenings. Univariate analysis examined associations between factors and PTSD at 1 year. The best fit multivariable logistic regression model led to a novel PTSD risk prediction tool based on weights assigned similar to the Charlson index methods.

Of 329 enrolled patients, 87 (26%) completed follow-up surveys; 58% screened positive for chronic PTSD. The best fit model predicting PTSD included age, insurance, violent mechanism, and 2 acute stress screening questions (AUC .89). Using these parameters, the maximum possible TIPPS index was 19. Those with PTSD at 1year had a mean TIPPS index of 12.9 ± 4.0, compared to 5.9 ± 4.2 for those who did not (

< .001).

Traumatic injury often leads to PTSD, which can be predicted by a novel risk score incorporating age, insurance status, violent injury mechanism, and acute stress reaction symptoms. Stability in life and relationships with primary care physicians may be protective of PTSD.

Diagnostic level II.

Diagnostic level II.The interaction of RB with chromatin is key to understanding its molecular functions. Here, for first time, we identify the full spectrum of chromatin-bound RB. Rather than exclusively binding promoters, as is often described, RB targets three fundamentally different types of loci (promoters, enhancers, and insulators), which are largely distinguishable by the mutually exclusive presence of E2F1, c-Jun, and CTCF. While E2F/DP facilitates RB association with promoters, AP-1 recruits RB to enhancers. Although phosphorylation in CDK sites is often portrayed as releasing RB from chromatin, we show that the cell cycle redistributes RB so that it enriches at promoters in G1 and at non-promoter sites in cycling cells. RB-bound promoters include the classic E2F-targets and are similar between lineages, but RB-bound enhancers associate with different categories of genes and vary between cell types. Thus, RB has a well-preserved role controlling E2F in G1, and it targets cell-type-specific enhancers and CTCF sites when cells enter S-phase.

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