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Background: Growing interest has motivated recent studies to examine differences in recovery after sport-related concussion (SRC) by sex. However, heterogeneity in study design, participants, and recovery outcomes has led to mixed findings. Further work is needed to evaluate potential differences by sex and to investigate the role of related characteristics, such as sport contact-level, in recovery timelines. This study aimed to investigate whether concussion recovery trajectories differ by sex, considering a priori clinical and demographic covariates, and accounting for the sequence of recovery outcomes. Our secondary question was whether sport contact-level modifies the relationship between sex and time to outcomes. Using data from the Ivy League–Big Ten Epidemiology of Concussion Study, we included SRCs reported across five academic years; 2015–2020 (February 2020). We used Cox proportional hazards regressions to estimate associations between sex and time from injury to three outcomes: (1) symptom resolution, (2) return to academics, (3) return to full play, accounting for measured confounders. Results: Among 1160 SRCs (male, n = 667; female, n = 493) with complete data, median age overall was 20 years (25th-75th percentiles:19–21), and most occurred among athletes playing high-contact sports (78.0%). Males were slightly more likely to complete symptom resolution over time compared to females (HR = 1.18, 95%CI = 1.05–1.33), but results were attenuated in fully adjusted models (HR 1.13, 95%CI = 0.99–1.29). Similarly, the HR of full academic return for males compared to females was 1.22 (95%CI = 1.07–1.38), but was attenuated in fully adjusted models (HR = 1.11, 95%CI = 0.97–1.28). The HR of full return to play for males compared to females was 1.14 (95%CI = 1.02–1.28), and was attenuated after adjustment (HR = 1.06, 95%CI = 0.93–1.20) as well. The interaction between sex and playing a high/low-contact sport was not statistically significant across models, though differences were apparent. Conclusions: Among a cohort of collegiate athletes with SRC, recovery timelines appeared similar between male and female athletes, adjusting for measured confounders. Differences by sex, considering sport contact-level, were evident and may be important clinically and in future studies. This study used robust methods, accounting for nesting in the sequence of RTP outcomes. Results inform concussion management protocols and planned qualitative work to further elucidate how collegiate athletes experience concussion recovery. Key Points: Heterogeneity in study design, participants, and recovery outcomes has led to mixed findings in determining differences in recovery trajectories after concussion by sex. We found that having longer time to symptom resolution, and also the sequence of having academic return before symptoms resolve and longer time to academic return were confounders in the relationship between sex and RTP timelines. Time to sequential recovery outcomes appeared similar between male and female athletes, adjusting for observable confounders. Further differences by sex were evident when considering contact-level, and may be important to consider clinically and in future research. Results indicate that differences in concussion recovery trajectories by sex may be largely attributed to and driven by differences in sports with a men's or women's team only, such as football, and this should be explored further. [ABSTRACT FROM AUTHOR]

Background: Disparities in cervical cancer screening rates among marginalized groups is a driver of inequalities in cervical cancer. Self‐sampling for human papillomavirus (HPV) testing is a newly emerging alternative to clinician‐performed testing to screen for cervical cancer, and has high potential to reduce screening barriers in under‐screened and marginalized groups. We study the acceptability in of HPV self‐sampling and informational materials among Black/African American, Hispanic/Spanish speaking, American Indian/Alaska Native and transgender/nonbinary populations. Methods: We conducted qualitative interviews with patients, ages 30–65, who were Black/African American, Hispanic, American Indian, and/or transgender/nonbinary individuals assigned female at birth. Telephone interviews were conducted in English or Spanish. Patients did not complete the test, rather were asked about the attractiveness, comprehensibility, and acceptability of the HPV self‐test, instructions, and messaging. Results: Among 23 completed interviews (5 American Indian/Alaska Native, 7 Hispanic [2 bilingual, 5 Spanish‐speaking], 5 Black/African American, and 6 transgender/nonbinary), patients from all groups thought the test was straightforward and convenient, and they would complete the test at home or in clinic. The transgender/nonbinary patients preferred at‐home testing. American Indian and transgender/nonbinary patients liked that the test might avoid pain, discomfort, and invasiveness. All patients liked the letter and instructions. All groups had specific suggestions for making the materials more culturally acceptable. Conclusions: The HPV self‐test and the instructions and materials for use were acceptable for a diverse group of patients. Tailored outreach and messaging should be considered to reduce screening disparities among groups that have been historically underserved by the medical system. [ABSTRACT FROM AUTHOR]

Introduction: Human Herpesvirus 6B (HHV-6B) impedes host immune responses by downregulating class I MHC molecules (MHC-I), hindering antigen presentation to CD8+ T cells. Downregulation of MHC-I disengages inhibitory receptors on natural killer (NK) cells, resulting in activation and killing of the target cell if NK cell activating receptors such as NKG2D have engaged stress ligands upregulated on the target cells. Previous work has shown that HHV-6B downregulates three MHC-like stress ligands MICB, ULBP1, and ULBP3, which are recognized by NKG2D. The U20 glycoprotein of the related virus HHV-6A has been implicated in the downregulation of ULBP1, but the precise mechanism remains undetermined. Methods: We set out to investigate the role of HHV-6B U20 in modulating NK cell activity. We used HHV-6B U20 expressed as a recombinant protein or transduced into target cells, as well as HHV-6B infection, to investigate binding interactions with NK cell ligands and receptors and to assess effects on NK cell activation. Small-angle X-ray scattering was used to align molecular models derived from machine-learning approaches. Results: We demonstrate that U20 binds directly to ULBP1 with sub-micromolar affinity. Transduction of U20 decreases NKG2D binding to ULBP1 at the cell surface but does not decrease ULBP1 protein levels, either at the cell surface or in toto. HHV-6B infection and soluble U20 have the same effect. Transduction of U20 blocks NK cell activation in response to cell-surface ULBP1. Structuralmodeling of the U20 - ULBP1 complex indicates some similarities to the m152-RAE1g complex. [ABSTRACT FROM AUTHOR]

Objective: To identify distinct subgroups of veterans with mild traumatic brain injury (mTBI) based on configurations of postconcussive symptom (PCS) endorsement, and to examine predictors of subgroup membership. Setting: Outpatient Veterans Health Administration (VHA). Participants: Veterans with clinician-confirmed mTBI who completed the Neurobehavioral Symptom Inventory (NSI), determined using the Comprehensive Traumatic Brain Injury Evaluation database. Individuals who tended to overreport symptoms were excluded via an embedded symptom validity scale. Design: Retrospective cohort study leveraging national VHA clinical data from 2012 to 2020. Latent class analysis (LCA) with a split-sample cross-validation procedure was used to identify subgroups of veterans. Multinomial logistic regression was used to examine predictors of subgroup membership. Main Measures: Latent classes identified using NSI items. Results: The study included 72 252 eligible veterans, who were primarily White (73%) and male (94°/o). The LCA supported 7 distinct subgroups of veterans with mTBI, characterized by diverging patterns of risk for specific PCS across vestibular (eg, dizziness), somatosensory (eg, headache), cognitive (eg, forgetfùlness), and mood domains (eg, anxiety). The most prevalent subgroup was Global (20.7%), followed by Cognitive-Mood (16.3%), Headache-Cognitive-Mood (H-C-M; 16.3%), Headache-Mood (14.2%), Anxiety (13.8%), Headache-Sleep (10.3%), and Minimal (8.5%). The Global class was used as the reference class for multinomial logistic regression because it was distinguished from others based on elevated risk for PCS across all domains. Female (vs male), Black (vs White), and Hispanic veterans (vs non-Hispanic) were less likely to be members of most subgroups characterized by lesser PCS endorsement relative to the Global class (excluding Headache-Mood). Conclusion: The 7 distinct groups identified in this study distill heterogenous patterns of PCS endorsement into clinically actionable phenotypes that can be used to tailor clinical management of veterans with mTBI. Findings reveal empirical support for potential racial, ethnic, and sex-based disparities in PCS among veterans, informing efforts aimed at promoting equitable recovery from mTBI in this population. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions The rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in‐progress effort to overcome these challenges with cooperative, systematic data extraction and validation.A multi‐disciplinary team of investigators collaborated to create the Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) Project dataset, which captures EHR data from six hospitals within the University of Pennsylvania Health System. Analysts and clinical researchers jointly iteratively reviewed SQL queries and their output to validate desired data elements. Data from patients aged ≥18 years with at least one encounter at an acute care hospital or hospice occurring since 7/1/2017 were included. The CIRCE Project includes three layers: (1) raw data comprised of direct SQL query output, (2) cleaned data with errors removed, and (3) transformed data with standardized implementations of commonly used case definitions and clinical scores.Between July 1, 2017 and December 31, 2023, the dataset captured 1 629 920 encounters from 740 035 patients. Most encounters were emergency department only visits (n = 965 834, 59.3%), followed by inpatient admissions without an intensive care unit admission (n = 518 367, 23.7%). The median age was 46.9 years (25th–75th percentiles = 31.1–64.7) at the time of the first encounter. Most patients were female (n = 418 303, 56.5%), a significant proportion were of non‐White race (n = 272 018, 36.8%), and 54 625 (7.4%) were of Hispanic/Latino ethnicity.The CIRCE Project represents a novel cooperative research model to capture clinically validated EHR data from a large diverse academic health system in the greater Philadelphia region and is designed to facilitate collaboration and data sharing to support learning health system activities. Ultimately, these data will be de‐identified and converted to a publicly available resource. [ABSTRACT FROM AUTHOR]

Once the fit of the cast metal framework on a removable partial denture (RPD) has been verified, the manufacturer's prefabricated denture teeth are typically secured on the cast metal framework to prepare for a wax evaluation. Although prefabricated denture teeth are available in different tooth forms and sizes, they require modification to fit an edentulous space. In arches with severe space discrepancy, it may be inefficient and time-consuming to make modifications to prefabricated denture teeth. The technique described uses digital technology to fabricate custom denture teeth on a cast metal framework and establish harmonious occlusion. An edentulous space with more than a single tooth replacement is designed as a splinted fixed partial denture with a connector. The designed teeth are milled in the double-cross-linked polymer to prepare for a wax evaluation, and once verified, the RPD is processed by using heat polymerization. Modifications are made to the milled denture teeth after wax elimination to reduce the likelihood of acrylic resin bond failure. [ABSTRACT FROM AUTHOR]

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive evidence that de novo mutations in SLC1A2 and CACNA1A cause specific EEs and expand the compendium of clinically relevant genotypes for GABRB3. We also identified EEs caused by genetic variants in ALG13, DNM1, and GNAO1 and report a mutation in IQSEC2. Notably, recurrent mutations accounted for 7/17 of the pathogenic variants identified. As a result of high-depth coverage, parental mosaicism was identified in two out of 14 cases tested with mutant allelic fractions of 5%-6% in the unaffected parents, carrying significant reproductive counseling implications. These results confirm that dysregulation in diverse cellular neuronal pathways causes EEs, and they will inform the diagnosis and management of individuals with these devastating disorders.

The ancestral centromeres of maize contain long stretches of the tandemly arranged CentC repeat. The abundance of tandem DNA repeats and centromeric retrotransposons (CR) has presented a significant challenge to completely assembling centromeres using traditional sequencing methods. Here, we report a nearly complete assembly of the 1.85 Mb maize centromere 10 from inbred B73 using PacBio technology and BACs from the reference genome project. The error rates estimated from overlapping BAC sequences are 7 × 10(-6) and 5 × 10(-5) for mismatches and indels, respectively. The number of gaps in the region covered by the reassembly was reduced from 140 in the reference genome to three. Three expressed genes are located between 92 and 477 kb from the inferred ancestral CentC cluster, which lies within the region of highest centromeric repeat density. The improved assembly increased the count of full-length CR from 5 to 55 and revealed a 22.7 kb segmental duplication that occurred approximately 121,000 years ago. Our analysis provides evidence of frequent recombination events in the form of partial retrotransposons, deletions within retrotransposons, chimeric retrotransposons, segmental duplications including higher order CentC repeats, a deleted CentC monomer, centromere-proximal inversions, and insertion of mitochondrial sequences. Double-strand DNA break (DSB) repair is the most plausible mechanism for these events and may be the major driver of centromere repeat evolution and diversity. In many cases examined here, DSB repair appears to be mediated by microhomology, suggesting that tandem repeats may have evolved to efficiently repair frequent DSBs in centromeres.

Wood chips, together with crop straw and manure, were demonstrated as feasible amendments for improving overall soil health and enhancing plant growth in severely desertified areas in Northern China in our previous studies. However, the effects of their mixtures are unclear. In this study, we evaluated the effect of three different amendment materials, when used alone and in combination, on physical, chemical, and biological properties of desertified soil and on the associated growth of alfalfa in Ningxia, Northern China. Four replicate microcosms were set up containing sandy soil mixed with 3% (w/w) of each of the following treatments: cow manure (CM), corn straw (CS), and poplar branches (PB) and their mixtures CS-PB, CM-PB, CM-CS, and CM-CS-PB. Measurements were conducted 7 and 15 months after the start of the experiment. Results showed, as a whole, treatment CS-PB improved soil physical properties more than other amendments during the whole experimental period, compared with control. However, the best establishment of alfalfa in the first year and best growth in the second year occurred in the CM-CS-PB treatment. Moreover, available N and urease were the most important driving factors affecting alfalfa growth during the whole experimental period, as shown by redundancy analysis. However, interestingly, the CM-CS-PB also functioned better in maintaining N supply and accelerating microbial activity than the other amendments. Therefore, we concluded that wood chips have a unique advantage in improving overall soil health and alfalfa growth when combined with straw and manure as new amendments. Additional keywords: corn straw, cow manure, desertified soil, organic amendments, poplar branches. Received 15 May 2019, accepted 10 March 2020, published online 20 April 2020, Introduction A critical challenge facing the world is determining how to feed the exponentially increasing human population in the coming decades. Estimates are that agriculture will have to increase production [...]

Feedback is an important aspect of the learning process. The immediate feedback assessment technique (IF-AT®) form allows students to receive feedback on their answers during a testing event. Studies with introductory psychology students supported both perceived and real student learning gains when this form was used with testing. Knowing that negative student perceptions of innovative classroom techniques can create roadblocks, this research focused on gathering student responses to using IF-AT® forms for testing in general chemistry 1 and organic chemistry 2 classes at several institutions. Students' perceptions on using the IF-AT® forms and how it influenced their thinking were gathered from a 16-item survey. The results of the student surveys are detailed and implementation strategies for using IF-AT® forms for chemistry testing are also outlined in this article.

UnlabelledTMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries, we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal transition phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.SignificanceThe vast majority of prostate cancer deaths are due to metastasis. Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through mechanisms involving the HGF-c-MET axis. Therapeutic approaches directed toward inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in patients with prostate cancer.

4-trans-[(18)F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[(18)F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[(18)F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[(18)F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[(18)F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[(18)F]mefway to 4-trans-[(18)F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[(18)F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[(18)F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[(18)F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[(18)F]mefway suggests the lower BPND of 3-[(18)F]mefway is due to a lower affinity. The lower affinity of 3-[(18)F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained.

A theoretical paper based on chiral micropolar effective‐medium theory suggested the possibility of unusual roton‐like acoustical‐phonon dispersion relations in 3D elastic materials. Here, as a first novelty, the corresponding inverse problem is solved, that is, a specific 3D chiral elastic metamaterial structure is designed, the behavior of which follows this effective‐medium description. The metamaterial structure is based on a simple‐cubic lattice of cubes, each of which not only has three translational but also three rotational degrees of freedom. The additional rotational degrees of freedom are crucial within micropolar elasticity. The cubes and their degrees of freedom are coupled by a chiral network of slender rods. As a second novelty, this complex metamaterial is manufactured in polymer form by 3D laser printing and its behavior is characterized experimentally by phonon‐band‐structure measurements. The results of these measurements, microstructure finite‐element calculations, and solutions of micropolar effective‐medium theory are in good agreement. The roton‐like dispersion behavior of the lowest phonon branch results from two aspects. First, chirality splits the transverse acoustical branches as well as the transverse optical branches. Second, chirality leads to an ultrastrong coupling and hybridization of chiral acoustical and optical phonons at finite wavevectors. [ABSTRACT FROM AUTHOR]