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We previously published a novel strategy for management of postcraniotomy bone flap infection consisting of single stage debridement, bone flap removal, and immediate titanium mesh cranioplasty.Postcraniotomy patients with surgical site infections treated with surgical debridement, bone flap removal, and immediate titanium mesh cranioplasty were retrospectively reviewed. The primary outcome measure was reoperation due to persistent infection or wound healing complications from the titanium mesh.We included 48 patients, of which 15 (31.3%) were female. The most common primary diagnoses were glioblastoma (31.3%), meningioma (18.8%), and vascular/trauma (16.7%). Most patients had a history of same-site craniotomy prior to the surgery complicated by surgical site infection and 47.9% had prior cranial radiation. Thirty-six (75.0%) patients achieved resolution of their infection and did not require a second operation. Twelve (25.0%) patients required reoperation: 6 (12.5%) patients were found to have frank intraoperative purulence on reoperation, whereas 6 (12.5%) had reoperation for poor wound healing without any evidence of persistent infection. Cochran Armitage trend test revealed that patients with increasing number of wound healing risk factors had significantly higher risk of reoperation (P = 0.001). Prior intensity modulated radiotherapy alone was a significant risk factor for reoperation (6.5 [1.40-30.31], P = 0.002). Median follow-up time was 20.5 weeks.Immediate titanium mesh cranioplasty at the time of debridement and bone flap removal is an acceptable option in the management of post-craniotomy bone flap infection. Patients with multiple wound healing risk factors are at higher risk for reoperation.

The COVID-19 pandemic is an ongoing stressor that has resulted in the exacerbation of mental health problems worldwide. However, longitudinal studies that identify preexisting behavioral and neurobiological factors associated with mental health outcomes during the pandemic are lacking. Here, we examined associations between prepandemic coping strategy engagement and frontolimbic circuitry with internalizing symptoms during the pandemic. In 85 adults (71.8% female; age 18-30 years), we assessed prototypically adaptive coping strategies (Connor-Davidson Resilience Scale), resting-state functional magnetic resonance imaging functional connectivity (FC) of frontolimbic circuitry, and depression and anxiety symptoms (Beck Depression Inventory, Screen for Child Anxiety-Related Emotional Disorders-Adult, respectively). We conducted general linear models to test preregistered hypotheses that (1) lower coping engagement prepandemic and (2) weaker frontolimbic FC prepandemic would predict elevated symptoms during the pandemic; and (3) coping would interact with FC to predict symptoms during the pandemic. Depression and anxiety symptoms worsened during the pandemic (ps.001). Prepandemic adaptive coping engagement and frontolimbic FC were not associated with depression or anxiety symptoms during the pandemic (uncorrected ps.05). Coping interacted with insula-rostral anterior cingulate cortex (ACC) FC (p = .003, pFDR = .014) and with insula-ventral ACC FC (p.001, pFDR.001) to predict depression symptoms, but these findings did not survive FDR correction after removal of outliers. Findings from our preregistered study suggest that specific prepandemic factors, particularly adaptive coping and frontolimbic circuitry, are not robustly associated with emotional responses to the pandemic. Additional studies that identify preexisting neurobehavioral factors implicated in mental health outcomes during global health crises are needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

This study compared perioperative outcomes among infants undergoing repair of congenital anomalies using minimally invasive (MIS) versus open surgical approaches.The ACS NSQIP Pediatric (2013-2018) was queried for patients undergoing repair of any of the following 9 congenital anomalies: congenital lung lesion (LL), mediastinal mass (MM), congenital malrotation (CM), anorectal malformation (ARM), Hirschsprung disease (HD), congenital diaphragmatic hernia (CDH), tracheoesophageal fistula (TEF), hepatobiliary anomalies (HB), and intestinal atresia (IA). Inverse probability of treatment weights (IPTW) derived from propensity scores were utilized to estimate risk-adjusted association between surgical approach and 30-day outcomes.12,871 patients undergoing congenital anomaly repair were included (10,343 open; 2528 MIS). After IPTW, MIS was associated with longer operative time (difference; 95% CI) (16 min; 9-23) and anesthesia time (13 min; 6-21), but less postoperative ventilation days (-1.0 days; -1.4- -0.6) and shorter postoperative length of stay (-1.4 days; -2.4- -0.3). MIS repairs had decreased risk of any surgical complication (risk difference: -6.6%; -9.2- -4.0), including hematologic complications (-7.3%; -8.9- -5.8). There was no significant difference in risk of complication when hematologic complications were excluded (RD -2.3% [-4.7%, 0.1%]). There were no significant differences in the risk of unplanned reoperation (0.4%; -1.5-2.2) or unplanned readmission (0.2%; -1.2-1.5).MIS repair of congenital anomalies is associated with improved perioperative outcomes when compared to open. Additional studies are needed to compare long-term functional and disease-specific outcomes.In this propensity-weighted multi-institutional analysis of nine congenital anomalies, minimally invasive surgical repair was associated with improved 30-day outcomes when compared to open surgical repair.III.

Telehealth was rapidly adopted during the COVID-19 pandemic. A survey was distributed to neurosurgeons in the United States (U.S.) to understand its use within neurosurgery, what barriers exist, unique issues related to neurosurgery, and opportunities for improvement.A survey was distributed via email and used the SurveyMonkey platform. The survey was sent to 3828 practicing neurosurgeons within the U.S., 404 responses were collected between October 30, 2021 and December 4, 2021.During the pandemic, telehealth was used multiple times per week by 60.65% and used daily by an additional 12.78% of respondents. A supermajority (89.84%) of respondents felt that evaluating patients across state lines with telemedicine is beneficial. Most respondents (95.81%) believed that telehealth improves patient access to care. The major criticism of telehealth was the inability to perform a neurological exam.Telehealth has been widely implemented within the field of neurosurgery during the COVID-19 pandemic and has increased access to care. It has allowed patients to be evaluated remotely, including across state lines. While certain aspects of the neurological exam are suited for video evaluation, sensation and reflexes cannot be adequately assessed. Neurosurgeons believe that telehealth adds value to their ability to deliver care.

Sepsis is a major health issue and a leading cause of death in hospitals globally. The treatment of sepsis is largely supportive and there are no therapeutics available that target the underlying pathophysiology of the disease. The development of therapeutics for the treatment of sepsis is hindered by the heterogeneous nature of the disease. The presence of multiple, distinct immune phenotypes ranging from hyperimmune to immunosuppressed can significantly impact the host response to infection. Recently, omics, biomarkers, cell surface protein expression and immune cell profiles have been utilized to classify immune status of sepsis patients. However, there has been limited studies of immune cell function during sepsis and even fewer correlating omics and biomarker alterations to functional consequences. In this review, we will discuss how the heterogeneity of sepsis and associated immune cell phenotypes result from changes in the omic make-up of cells and its correlation with leukocyte dysfunction. We will also discuss how emerging techniques such as in silico modeling and machine learning can help in phenotyping sepsis patients leading to precision medicine.

Although the presence of catenanes (i.e., intermolecular tangles) in chromosomal DNA stabilizes interactions between daughter chromosomes, a lack of resolution can have serious consequences for genomic stability. In all species, from bacteria to humans, type II topoisomerases are the enzymes primarily responsible for catenating/decatenating DNA. DNA topology has a profound influence on the rate at which these enzymes alter the superhelical state of the double helix. Therefore, the effect of supercoil handedness on the ability of human topoisomerase IIα and topoisomerase IIβ and bacterial topoisomerase IV to catenate DNA was examined. Topoisomerase IIα preferentially catenated negatively supercoiled over positively supercoiled substrates. This is opposite to its preference for relaxing (i.e., removing supercoils from) DNA and may prevent the enzyme from tangling the double helix ahead of replication forks and transcription complexes. The ability of topoisomerase IIα to recognize DNA supercoil handedness during catenation resides in its C-terminal domain. In contrast to topoisomerase IIα, topoisomerase IIβ displayed little ability to distinguish DNA geometry during catenation. Topoisomerase IV from three bacterial species preferentially catenated positively supercoiled substrates. This may not be an issue, as these enzymes work primarily behind replication forks. Finally, topoisomerase IIα and topoisomerase IV maintain lower levels of covalent enzyme-cleaved DNA intermediates with catenated over monomeric DNA. This allows these enzymes to perform their cellular functions in a safer manner, as catenated daughter chromosomes may be subject to stress generated by the mitotic spindle that could lead to irreversible DNA cleavage.

The novel quaternary thiogermanate Li4CdGe2S7 (tetralithium cadmium digermanium heptasulfide) was discovered from a solid-state reaction at 750 °C. Single-crystal X-ray diffraction data were collected and used to solve and refine the structure. Li4CdGe2S7 is a member of the small, but growing, class of I4–II–IV2–VI7 diamond-like materials. The compound adopts the Cu5Si2S7 structure type, which is a derivative of lonsdaleite. Crystallizing in the polar space group Cc, Li4CdGe2S7 contains 14 crystallographically unique ions, all residing on general positions. Like all diamond-like structures, the compound is built of corner-sharing tetrahedral units that create a relatively dense three-dimensional assembly. The title compound is the major phase of the reaction product, as evidenced by powder X-ray diffraction and optical diffuse reflectance spectroscopy. While the compound exhibits a second-harmonic generation (SHG) response comparable to that of the AgGaS2 (AGS) reference material in the IR region, its laser-induced damage threshold (LIDT) is over an order of magnitude greater than AGS for λ = 1.064 µm and τ = 30 ps. Bond valence sums, global instability index, minimum bounding ellipsoid (MBE) analysis, and electronic structure calculations using density functional theory (DFT) were used to further evaluate the crystal structure and electronic structure of the compound and provide a comparison with the analogous I2–II–IV–VI4 diamond-like compound Li2CdGeS4. Li4CdGe2S7 appears to be a better IR nonlinear optical (NLO) candidate than Li2CdGeS4 and one of the most promising contenders to date. The exceptional LIDT is likely due, at least in part, to the wider optical bandgap of ∼3.6 eV.

Intracranial aneurysms are present in up to 18% of arteriovenous malformations (AVMs) and increase the risk of intracranial hemorrhage. No consensus exists on the optimal treatment strategy for AVM-associated aneurysms. The goal of this study was to systematically review endovascular treatment methods of AVM-associated intracranial aneurysms, radiographic outcomes, and periprocedural complications.A systematic review was performed in accordance with PRISMA guidelines to identify studies that investigated the use of endovascular treatments for management of patients with AVM-associated aneurysms. Collected variables included aneurysm and AVM location, aneurysm size and characteristics, AVM and aneurysm treatment modality, periprocedural complications, and long-term clinical and radiographic outcomes.Eight studies with 237 patients and 314 AVM-associated intracranial aneurysms were included. Two-hundred and twenty-four aneurysms were flow-related (71.3%), 80 were intranidal (25.5%), and 10 were unrelated (3.2%). Complete occlusion was 56.3% (18/32) for aneurysmal coil embolization and 99% (104/105) for parent vessel sacrifice. Of the 13 aneurysms treated with ethanol sclerotherapy, 8 were successfully obliterated (8/13; 61%) using ethanol sclerotherapy alone and the rest required adjunct endovascular embolization for obliteration of the artery and associated aneurysm. The periprocedural complication rate was approximately 12% and consisted of ischemic symptoms, intracranial hemorrhage, and coiling complications.Endovascular management options of AVM-associated intracranial aneurysms are limited and mostly comprised primary aneurysmal coil embolization or parent vessel sacrifice using coils or liquid embolics. Embolization strategy depends on factors such as AVM angioarchitecture, rupture status, and adjunct AVM treatments.

Lay Summary In this retrospective cohort study, we demonstrated that dose intensification of ustekinumab to every 4 or every 6 weeks was effective in both achieving and maintaining clinical remission for >40% of inflammatory bowel disease patients for up to 24 months.

How police officers exercise their unique power to use deadly force continues to be a topic of interest among academics and has recently become arguably the most visible public policy issue related to the criminal justice system in the United States. Academic interest in officers’ use of deadly force includes attention to how officers make the decision to discharge their firearms during encounters with citizens. Binder and Scharf posited that actions and decisions made by officers early in a high-risk police-citizen encounter can impact their decision to use deadly force at the conclusion of the encounter. This decision-making model, however, has been subject to very little empirical scrutiny in the decades since it was proposed (see Fridell & Binder; Scharf & Binder for notable exceptions). To bring their comprehensive framework back to the forefront and provide additional empirical assessment, the authors used the Binder and Scharf model as a framework to examine 82 officers’ decisions to shoot or hold fire in incidents that involved multiple officers who ultimately made different decisions regarding lethal force. Results from the qualitative analysis suggest that the presence and actions of other officers on scene can have a notable impact on officers’ decision-making during a high-risk police-citizen encounter. Furthermore, findings from this study extend the Binder-Scharf model by highlighting the role of conscious and unconscious decision-making and the impact of social roles on officers’ choices during an officer-involved shooting.

Viruses in the family Rhabdoviridae infect a variety of hosts, including vertebrates, invertebrates, plants and fungi, with important consequences for health and agriculture. This study describes two newly discovered viruses of freshwater mussels from the United States.

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Real-world data comparing the effectiveness of tofacitinib to ustekinumab are limited. We compared 52-week outcomes of tofacitinib vs ustekinumab for UC after antitumor necrosis factor (anti-TNF) failure. Methods In this retrospective cohort study, adults initiated tofacitinib or ustekinumab for UC after anti-TNF failure May 1, 2018 to April 1, 2021, at a US academic medical center. The primary outcome was steroid-free clinical remission (SFCR) at 12 and 52 weeks. The secondary outcome was drug survival (ie, time to drug discontinuation due to nonresponse). Adverse events (AEs) were also assessed. Results Sixty-nine patients initiated tofacitinib, and 97 patients initiated ustekinumab with median follow-up of 88.0 and 62.0 weeks, respectively. After inverse probability of treatment-weighted logistic and Cox regression, there was no association of tofacitinib vs ustekinumab with SFCR at 12 weeks (odds ratio, 1.65; 95% CI, 0.79-3.41), SFCR at 52 weeks (odds ratio, 1.14; 95% CI, 0.55-2.34), or drug survival (hazard ratio, 1.37; 95% CI, 0.78-2.37). Kaplan-Meier analysis demonstrated no separation in drug survival curves. Regression results were similar after excluding patients with prior tofacitinib or ustekinumab exposure. During available follow-up, 17 AEs were reported for tofacitinib (most commonly shingles, n = 4), and 10 AEs were reported for ustekinumab (most commonly arthralgia and rash, each n = 2). Two patients discontinued treatment due to AEs (1 tofacitinib for elevated liver enzymes, 1 ustekinumab for arthralgia). Conclusions In a real-world UC cohort, tofacitinib and ustekinumab demonstrated similar effectiveness at 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

Japanese encephalitis virus (JEV), a zoonotic flavivirus, is principally transmitted by hematophagous mosquitoes, continually between susceptible animals and incidentally from those animals to humans. For almost a century since its discovery, JEV was geographically confined to the Asia-Pacific region with recurrent sizable outbreaks involving wildlife, livestock, and people. However, over the past decade, it has been detected for the first time in Europe (Italy) and Africa (Angola) but has yet to cause any recognizable outbreaks in humans. JEV infection leads to a broad spectrum of clinical outcomes, ranging from asymptomatic conditions to self-limiting febrile illnesses to life-threatening neurological complications, particularly Japanese encephalitis (JE). No clinically proven antiviral drugs are available to treat the development and progression of JE. There are, however, several live and killed vaccines that have been commercialized to prevent the infection and transmission of JEV, yet this virus remains the main cause of acute encephalitis syndrome with high morbidity and mortality among children in the endemic regions. Therefore, significant research efforts have been directed toward understanding the neuropathogenesis of JE to facilitate the development of effective treatments for the disease. Thus far, multiple laboratory animal models have been established for the study of JEV infection. In this review, we focus on mice, the most extensively used animal model for JEV research, and summarize the major findings on mouse susceptibility, infection route, and viral pathogenesis reported in the past and present, and discuss some unanswered key questions for future studies.

ImportanceThe prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.ObservationsWe describe the protocol for the Pediatric Observational Cohort Study of the NIH’sREsearchingCOVID toEnhanceRecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) ade novoRECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). Thede novocohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.Conclusions and RelevanceRECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.Clinical Trials.gov IdentifierClinical Trial Registration:http://www.clinicaltrials.gov. Unique identifier:NCT05172011

PurposeThe study aims to create a model to predict survival outcomes for non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT) using deep-learning segmentation based prognostication (DESEP).MethodsThe DESEP model was trained using imaging from 108 patients with NSCLC with various clinical stages and treatment histories. The model generated predictions based on unsupervised features learned by a deep-segmentation network from computed tomography imaging to categorize patients into high and low risk groups for overall survival (DESEP-predicted-OS), disease specific survival (DESEP-predicted-DSS), and local progression free survival (DESEP-predicted-LPFS). Serial assessments were also performed using auto-segmentation based volumetric RECISTv1.1 and computer-based unidimensional RECISTv1.1 patients was performed.ResultsThere was a concordance between the DESEP-predicted-LPFS risk category and manually calculated RECISTv1.1 (φ=0.544, p=0.001). Neither the auto-segmentation based volumetric RECISTv1.1 nor the computer-based unidimensional RECISTv1.1 correlated with manual RECISTv1.1 (p=0.081 and p=0.144, respectively). While manual RECISTv1.1 correlated with LPFS (HR=6.97,3.51-13.85, c=0.70, pConclusionDeep-learning segmentation based prognostication can predict LPFS as well as OS, and DSS after SBRT for NSCLC. It can be used in conjunction with current standard of care, manual RECISTv1.1 to provide additional insights regarding DSS and OS in NSCLC patients receiving SBRT.SummaryWhile current standard of care, manual RECISTv1.1 correlated with local progression free survival (LPFS) (HR=6.97,3.51-13.85, c=0.70, p

Predicted loss of function (pLoF) variants are highly deleterious and play an important role in disease biology, but many of these variants may not actually result in loss-of-function. Here we present a framework that advances interpretation of pLoF variants in research and clinical settings by considering three categories of LoF evasion: (1) predicted rescue by secondary sequence properties, (2) uncertain biological relevance, and (3) potential technical artifacts. We also provide recommendations on adjustments to ACMG/AMP guidelines’s PVS1 criterion. Applying this framework to all high-confidence pLoF variants in 22 autosomal recessive disease-genes from the Genome Aggregation Database (gnomAD, v2.1.1) revealed predicted LoF evasion or potential artifacts in 27.3% (304/1,113) of variants. The major reasons were location in the last exon, in a homopolymer repeat, in low per-base expression (pext) score regions, or the presence of cryptic splice rescues. Variants predicted to be potential artifacts or to evade LoF were enriched for ClinVar benign variants. PVS1 was downgraded in 99.4% (162/163) of LoF evading variants assessed, with 17.2% (28/163) downgraded as a result of our framework, adding to previous guidelines. Variant pathogenicity was affected (mostly from likely pathogenic to VUS) in 20 (71.4%) of these 28 variants. This framework guides assessment of pLoF variants beyond standard annotation pipelines, and substantially reduces false positive rates, which is key to ensure accurate LoF variant prediction in both a research and clinical setting.

Genetic regulatory networks (GRNs) regulate the flow of genetic information from the genome to expressed messenger RNAs (mRNAs) and thus are critical to controlling the phenotypic characteristics of cells. Numerous methods exist for profiling mRNA transcript levels and identifying protein-DNA binding interactions at the genome-wide scale. These enable researchers to determine the structure and output of transcriptional regulatory networks, but uncovering the complete structure and regulatory logic of GRNs remains a challenge. The field of GRN inference aims to meet this challenge using computational modeling to derive the structure and logic of GRNs from experimental data and to encode this knowledge in Boolean networks, Bayesian networks, ordinary differential equation (ODE) models, or other modeling frameworks. However, most existing models do not incorporate dynamic transcriptional data since it has historically been less widely available in comparison to “static” transcriptional data. We report the development of an evolutionary algorithm-based ODE modeling approach that integrates kinetic transcription data and the theory of attractor matching to infer GRN architecture and regulatory logic. Our method outperformed six leading GRN inference methods, none of which incorporate kinetic transcriptional data, in predicting regulatory connections among TFs when applied to a small-scale engineered synthetic GRN inSaccharomyces cerevisiae. Moreover, we demonstrate the potential of our method to predict unknown transcriptional profiles that would be produced upon genetic perturbation of the GRN governing a two-state cellular phenotypic switch inCandida albicans. We established an iterative refinement strategy to facilitate candidate selection for experimentation; the experimental results in turn provide validation or improvement for the model. In this way, our GRN inference approach can expedite the development of a sophisticated mathematical model that can accurately describe the structure and dynamics of thein vivoGRN.Author SummaryThe establishment of distinct transcriptional programs, where specific sets of genes are activated or repressed, is fundamental to all forms of life. Sequence-specific DNA-binding proteins, often referred to as regulatory transcription factors, form interconnected gene regulatory networks (GRNs) which underlie the establishment and maintenance of specific transcriptional programs. Since their discovery, many modeling approaches have sought to understand the structure and regulatory behaviors of these GRNs. The field of GRN inference uses experimental measurements of transcript abundance to predict how regulatory transcription factors interact with their downstream target genes to establish specific transcriptional programs. However, most prior approaches have been limited by the exclusive use of “static” or steady-state measurements. We have developed a unique approach which incorporates dynamic transcriptional data into a sophisticated ordinary differential equation model to infer GRN structures that give rise to distinct transcriptional programs. Our model not only outperforms six other leading models, it also is capable of accurately predicting how changes in GRN structure will impact the resulting transcriptional programs. These unique attributes of our model, combined with “real world” experimental validation of our model predictions, represent a significant advance in the field of gene regulatory network inference.

Black adults in the United States seek mental healthcare at a lesser rate than White adults, attributed in part to the stigma of seeking psychological help. Black men in need of mental health care face a double barrier associated with the intersection of their race and gender, as men report more negative attitudes toward help-seeking than do women. To understand help-seeking attitudes among Black men, this study examined the direct effects of traditional masculinity, traditional/Black masculinity, and Black masculinity on public stigma of help-seeking as well as the indirect effects on self-stigma of help-seeking and psychological help-seeking attitudes among a sample of Black men in the United States ( N = 160). Results demonstrated that Black masculinity and traditional/Black masculinity predicted greater public stigma, which predicted greater self-stigma and in turn less positive psychological help-seeking attitudes. This study also found an unexpected negative relationship between traditional masculinity and public stigma and an indirect positive effect on psychological help-seeking attitudes. Results support tailored stigma-reduction interventions for the Black community.

During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein–protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.

What is the central question of the study? Do peripheral and cerebral vascular function differ between young non-Hispanic Black men and women? What is the main finding and its importance? The non-Hispanic Black women in this study presented greater peripheral conduit artery and cerebrovascular reactivity, yet similar peripheral microvascular function relative to the non-Hispanic Black men. These preliminary findings suggest that young Black women and men possess divergent vascular function, possibly contributing to the unique non-Hispanic Black sex differences in cardiovascular and cerebrovascular diseases.In the USA, cardiovascular and cerebrovascular diseases remain more prominent in the non-Hispanic Black (BL) population relative to other racial/ethnic groups. Typically, sex differences emerge in the manifestation of these diseases, though these differences may not fully materialize in the BL population. While numerous mechanisms are implicated, differences in vascular function likely contribute. Research has demonstrated blunted vasodilatation in several vascular regions in BL versus non-Hispanic White individuals, though much of this work did not assess sex differences. Therefore, this study aimed to ascertain if indices of vascular function are different between young BL women (BW) and men (BM). Eleven BW and 15 BM (22 (4) vs. 23 (3) years) participated in this study. Each participant underwent testing for brachial artery flow-mediated dilatation (FMD), post-occlusive reactive hyperaemia and cerebral vasomotor reactivity during rebreathing-induced hypercapnia. BW exhibited greater adjusted FMD than BM (P 0.05 for all), but similar or lower reactive hyperaemia when assessed as blood velocity (P 0.39 for all) or blood flow reactivity (P 0.05 for all), respectively. Across a range of hypercapnia, BW had greater middle cerebral artery blood velocity and cerebrovascular conductance index than BM (P 0.001 for both). These preliminary data suggest that young BW have greater vascular function relative to young BM, though this was inconsistent across different indices. These findings provide insight into the divergent epidemiological findings between BM and BW. Further research is needed to elucidate possible mechanisms and relate these physiological responses to epidemiological observations.

PURPOSE: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration. METHODS: Over the past 10 years, the National Institutes of Health–supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution. RESULTS: We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Beyond generating a list of gene-phenotype relationships and participating in widespread data sharing, the CMGs have created resources, tools, and training for the larger community to foster understanding of genes and genome variation. The CMGs have participated in a wide range of data sharing activities, including deposition of all eligible CMG data into the Analysis, Visualization, and Informatics Lab-space (AnVIL), sharing candidate genes through the Matchmaker Exchange and the CMG website, and sharing variants in Genotypes to Mendelian Phenotypes (Geno2MP) and VariantMatcher. CONCLUSION: The work is far from complete; strengthening communication between research and clinical realms, continued development and sharing of knowledge and tools, and improving access to richly characterized data sets are all required to diagnose the remaining molecularly undiagnosed patients.

Introduction. The COVID-19 pandemic caused a pause to nearly all sporting activities in the spring of 2020, and collegiate athletes at the National Collegiate Athletic Association (NCAA)-affiliated universities whose sporting seasons were affected by the pandemic were granted an extra year of athletic eligibility. The study was conducted to determine how collegiate athletes planned to use an additional year of eligibility granted by the NCAA. Methods. The authors conducted a cross-sectional survey of 632 athletes from two universities in the Midwestern United States, between August and September 2021. The athletes completed an anonymous, 9-item survey to assess the effect of the pandemic on athletic season, athletic eligibility, and potential change in an academic or professional career. Chi-square tests, generalized linear mixed models, and adjusted odds ratio were used for the analyses. Results. The participation rate was 74.5% (471 of 632). Nearly 63% (290 of 461) of the athletes received an additional year of eligibility because of the pandemic, with 193 (66.6%) planned to use their extra year for scholastic development. Male athletes (65.3% vs 34.7%; χ2[1, n=290]=11.66, P

The horned dinosaur genus Torosaurus has a challenging history, relating both to its geographic distribution and taxonomy. Whereas Torosaurus has been reported from Upper Maastrichtian deposits in Canada, which would mark the northernmost range of the genus, recent work has questioned the generic identity of the implicated material, which primarily consists of a pair of cranial frills. Perhaps more problematically, the validity of the genus itself has been a subject of recent debate, with some arguing that Torosaurus is simply a skeletally mature growth form of the contemporaneous Triceratops. In this study, we describe and illustrate the relevant frill material from Canada, and determine that it is most plausibly attributable to the Torosaurus morph. Moreover, we apply for the first time osteohistological sampling to some postcranial material associated with one of the frills, and find that the animal was still growing at the time of death. This finding, in addition to other considerations presented here, leads us to conclude that Torosaurus is a valid genus, and is not simply a mature growth form of Triceratops.

We report the synthesis and characterization of two bidentate ligands containing an aliphatic monoprotic aminophosphine moiety, as well as novel complexes with Co(ii), Ni(ii), and Cu(ii).

This article reviews literature in composition studies since affective science's emergence in the 1980s. It focuses on composition studies’ history of adopting findings and theories from affective science, and distinguishes trends in how the field applies those elements in theoretical versus pedagogical contexts. While composition studies’ adoption of affective science in its theorizing has helped the field progress toward a “complete psychology of writing,” affective science's influence on classroom practices has not been so clear cut or direct. However, affective science is a fast-growing, liberal, and multidisciplinary field. As it progresses, composition studies continues to embrace its concepts and theories. This review notes the expectations and limitations developing through this dynamic interdisciplinary relationship.

A series of nitrated aza-BODIPYs on the 2- and 6-positions were regioselectively synthesized and their photophysical properties were examined.

Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects ∼5% of menstruating individuals. Although symptoms are limited to the luteal phase of the menstrual cycle, PMDD causes significant distress and impairment across a range of activities. PMDD is under-recognized by health care providers, can be difficult to diagnose, and lies at the intersection of gynecology and psychiatry. Thus, many patients are misdiagnosed, or encounter challenges in seeking care. The aim of this study was to examine patients' experiences with different health care specialties when seeking care for PMDD symptoms. Methods: We examined data from the 2018 Global Survey of Premenstrual Disorders conducted by the International Association for Premenstrual Disorders (IAPMD). Patients rated their health care providers (general practitioners, psychiatrists, gynecologists, psychotherapists) in three key areas related to treatment of premenstrual mood complaints: interpersonal factors, awareness and knowledge of PMDD, and whether the patient was asked to track symptoms daily. Intraclass correlations examined between- and within-person variance. Multilevel regression models predicted ratings on each provider competency item, with ratings nested within individuals to examine the within-patient effect of provider type on outcomes. Results: The sample included 2,512 patients who reported seeking care for PMDD symptoms. Regarding interpersonal factors, psychotherapists were generally rated the highest. On awareness and knowledge of PMDD, gynecologists and psychiatrists were generally rated the highest. Gynecologists were more likely than other providers to ask patients to track symptoms daily. Conclusions: These findings suggest that different providers have different strengths in assessing and treating PMDD. Further, graduate and medical training programs may benefit from increased curricular development regarding evidence-based evaluation and treatment of PMDD.

Filipino's love for the elderly is undeniable. However, despite the respect they have for the elderly, an increasing amount of elderly abandonment is rising in the Philippines. The drastic increase in statistics of abandonment will still grow over the years because aging is inevitable. The primary goal of this study is to dig deeper into the experiences, challenges, and coping mechanisms of abandoned senior citizens inside of a home for the aged to spread awareness about this certain topic. By the use of Interpretative Phenomenological Analysis, the study come up with the following findings: (1) The abandoned senior citizens chose to be inside the facility because they don't want to be a burden in their original homes. (2) Faith and religious works affect their psychological well-being. (3) Physical appearance does not affect their self-esteem. (4) Social support boosts their psychological well-being as well. (5) One of the biggest reasons why abandoned senior citizens left their homes is being neglected to cause them to leave and stay in home for the aged (6) Lastly, people inside the facilities accepted the fact that death is drawing closer to them but they don't want to die yet.

One of the main highlights from last year’s event was the 2022 Philippine National and Local Elections. The Philippine elections involve a lot of people interaction from poll workers and other deputized agencies. Further, this study explores the lived experiences, challenges, and coping mechanisms of poll watchers during the 2022 Philippine election. Employing the Interpretative Phenomenological Analysis, the findings of this study were: (1) Filipino workers value a good-paying job and preferred meaningful work. (2) Amidst the experiences and challenges, the poll watchers remain determined and motivated to take part in the seasonal election. (3) Poll watchers must be physically, emotionally, and mentally prepared to participate in this crucial work. Mainly, poll-watching is a self-reliant job.