Venous Thromboembolic Disease Genetics: From variants to function.

Venous thromboembolic disease (VTE) is a prevalent and potentially life-threatening vascular disease including both deep vein thrombosis and pulmonary embolism. This review will focus on recent insights into the heritable factors that influence an individual's risk for VTE. Here we will explore not only the discovery of new genetic risk variants but also the importance of functional characterization of these variants. These genome-wide studies should lead to a better understanding of the biological role of genes inside and outside of the canonical coagulation system in thrombus formation and lead to an improved ability to predict an individual's risk of VTE. Further understanding of the molecular mechanisms altered by genetic variation in VTE risk will be accelerated by further human genome sequencing efforts and the use of functional genetic screens.

Evaluating the robustness of parameter estimates in cognitive models: A meta-analytic review of multinomial processing tree models across the multiverse of estimation methods.

Researchers have become increasingly aware that data-analysis decisions affect results. Here, we examine this issue systematically for multinomial processing tree (MPT) models, a popular class of cognitive models for categorical data. Specifically, we examine the robustness of MPT model parameter estimates that arise from two important decisions: the level of data aggregation (complete-pooling, no-pooling, or partial-pooling) and the statistical framework (frequentist or Bayesian). These decisions span a multiverse of estimation methods. We synthesized the data from 13,956 participants (164 published data sets) with a meta-analytic strategy and analyzed the magnitude of divergence between estimation methods for the parameters of nine popular MPT models in psychology (e.g., process-dissociation, source monitoring). We further examined moderators as potential sources of divergence. We found that the absolute divergence between estimation methods was small on average (<.04; with MPT parameters ranging between 0 and 1); in some cases, however, divergence amounted to nearly the maximum possible range (.97). Divergence was partly explained by few moderators (e.g., the specific MPT model parameter, uncertainty in parameter estimation), but not by other plausible candidate moderators (e.g., parameter trade-offs, parameter correlations) or their interactions. Partial-pooling methods showed the smallest divergence within and across levels of pooling and thus seem to be an appropriate default method. Using MPT models as an example, we show how transparency and robustness can be increased in the field of cognitive modeling. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Trajectory of primordial follicle depletion is accelerated in obese mice in response to 7,12-dimethylbenz[a]anthracene exposure.

Both obesity and exposure to environmental genotoxicants, such as 7,12-dimethylbenz[a]anthracene (DMBA), negatively impair female reproductive health. Hyperphagic lean KK.Cg-a/a (n = 8) and obese KK.Cg-Ay/J (n = 10) mice were exposed to corn oil as vehicle control (CT) or DMBA (1 mg/kg/day) for 7d intraperitoneally, followed by a recovery period. Obesity increased liver and spleen weight (P < 0.05), and DMBA exposure decreased uterine weight (P < 0.05) in obese mice. Primordial follicle loss (P < 0.05) caused by DMBA exposure was observed in obese mice only. Primary (lean P < 0.1; obese P < 0.05) and secondary (lean P < 0.05, obese P < 0.1) follicle loss initiated by DMBA exposure continued across recovery. Reduced pre-antral follicle number in lean mice (P < 0.05), regardless of DMBA exposure, was evident with no effect on antral follicles or corpora lutea number. Immunofluorescence staining of DNA damage marker, γH2AX, did not indicate ongoing DNA damage but TRP53 abundance was decreased in follicles (P < 0.05) of DMBA-exposed obese mice. In contrast, increased (P < 0.05) superoxide dismutase was observed in the corpora lutea of DMBA-exposed obese mice and reduced (P < 0.05) TRP53 abundance was noted in preantral and antral follicles of DMBA-exposed obese mice. This study indicates that obesity influences ovotoxicity caused by a genotoxicant, potentially involving accelerated primordial follicle activation and hampering normal follicular dynamics.

Unintended Consequences of Code Status in the Intensive Care Unit: What Happens After a Do-Not-Resuscitate Order Is Placed? A Retrospective Cohort Study.

Background: Some clinicians suspect that patients with do-not-resuscitate (DNR) orders receive less aggressive care. Extrapolation from code status to goals of care could cause significant harm. This study asked the question: Do DNR orders in the intensive care unit (ICU) lead to a decrease in invasive interventions? Methods: This was a retrospective cohort study of ICU patients from three teaching hospitals. All ICU patients were assessed for inclusion. Exclusion criteria were medical futility and death, comfort care, or ICU discharge <48 hours after DNR initiation. Five hundred thirty-six patients met inclusion criteria. One hundred forty-five were included in the final analysis. Primary outcomes were occurrence of invasive interventions after DNR initiation-surgical operation, central line, ventilation, dialysis, or other procedure. Secondary outcomes were antibiotic administration, blood transfusion, mortality, and discharge location. Results: Patients with DNR orders underwent fewer surgical operations (14.5% vs. 31.1%, p = 0.002), but more central lines (42.1% vs. 23.0%, p = 0.009), ventilator use (49.0% vs. 18.9%, p < 0.001), and dialysis (20.0% vs. 4.1%, p = 0.002), compared with patients without DNR orders. Transfusions and antibiotic use decreased similarly over admission for both groups (transfusions: ß = 1.25; p = 0.59; and antibiotics: ß = 1.44; p = 0.27). Mortality and hospice discharges were higher for DNR patients (p < 0.001.). Conclusions: DNR status did not decrease the number of nonoperative interventions patients received as compared with full code counterparts. Although differences in populations existed, patients with DNR orders were likely to receive a similar number of invasive interventions. This finding suggests that providers do not wholesale limit these options for patients with code status limitations.

Patterns of mean age at drug use initiation by race and ethnicity, 2004-2019.

INTRODUCTION: Adolescent drug use can result in clinically significant psychiatric outcomes later in life mitigated by targeted prevention strategies. While mean age of drug initiation has increased over time, there is little research of mean age of drug initiation among adolescents by race/ethnicity. METHODS: The study used the National Survey on Drug Use and Health data (2004-2019). Sample included individuals aged 12 to 21 years. Year-by-year drug use initiation (i.e., first-time use within the past year) trends examined for each drug by race/ethnicity using jointpoint regression. RESULTS: Sample included 95,022 initiates for any of 18 drugs. Year-by-year mean initiation age significantly increased for alcohol (except Non-Hispanic [NH] White, 2004-2012), tobacco cigarettes (except NH American Indian/Alaska Native [AI/AN]), cigars, marijuana (except NH Asian or Pacific Islander, NH Multiracial), cocaine (except NH Black). Significant increase in mean initiation age found for heroin (Hispanic/Latinx only), hallucinogens (NH White, NH Black only), LSD (NH White only), methamphetamines (NH White only), smokeless tobacco (NH White, NH Black only), inhalants (only NH White, NH AI/AN; NH Multiracial, 2004-2011), sedatives (NH White, Hispanic/Latinx only), stimulants (NH White, Hispanic/Latinx only), and ecstasy (NH White, NH Black, Hispanic/Latinx only). Significant decrease in mean initiation age found for alcohol (only NH White, 2013-2019), smokeless tobacco (only Hispanic/Latinx, 2015-2019; NH AI/AN, 2012-2019), and inhalants (only NH Multiracial, 2012-2019). CONCLUSION: Mean initiation age differed widely by race/ethnicity. Mean initiation age in most racial/ethnic groups increased for several drugs including alcohol, marijuana, and tobacco products and decreased for some drugs such as inhalants. These findings could help inform groups to target for future prevention strategies.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.

Enhancing entomopathogenic nematode efficacy with Pheromones: A field study targeting the pecan weevil.

Consistent efficacy is required for entomopathogenic nematodes to gain wider adoption as biocontrol agents. Recently, we demonstrated that when exposed to nematode pheromone blends, entomopathogenic nematodes showed increased dispersal, infectivity, and efficacy under laboratory and greenhouse conditions. Prior to this study, the impact of entomopathogenic nematode-pheromone combinations on field efficacy had yet to be studied. Steinernema feltiae is a commercially available entomopathogenic nematode that has been shown to increase mortality in insect pests such as the pecan weevil Curculio caryae. In this study, the pecan weevil was used as a model system to evaluate changes in S. feltiae efficacy when treated with a partially purified ascaroside pheromone blend. Following exposure to the pheromone blend, the efficacy of S. feltiae significantly increased as measured with decreased C. caryae survival despite unfavorable environmental conditions. The results of this study highlight a potential new avenue for using entomopathogenic nematodes in field conditions. With increased efficacy, using entomopathogenic nematodes will reduce reliance on conventional management methods in pecan production, translating into more environmentally acceptable practices.

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars.

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful. Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer. Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included. Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index. Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer. Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

A Case Series of Ocular Syphilis Cases at Military Treatment Facility From 2020 to 2021.

Syphilis is a sexually transmitted infection, caused by the spirochete Treponema pallidum, that can lead to multi-organ involvement. In 2020, over 138,000 cases were reported in the United States equating to a case report of 40.8 per 100,000 people. Ocular syphilis is a rare manifestation and is defined as the clinical presentation of ocular disease in a person with laboratory-confirmed syphilis infection of any stage, with estimated incidence of 0.6-2% of all cases. Syphilis is known as "The Great Imitator," and can present as nearly any form of ocular disease, though the most common manifestations are posterior uveitis and panuveitis. The highly variable clinical presentation of ocular syphilis often leads to delayed diagnosis allowing the potential for poor, often preventable outcomes. This highlights the need for providers to have a high level of clinical suspicion and awareness of ocular manifestations of syphilis, especially in high risk populations. We present a case series of five patients diagnosed with ocular syphilis at a military treatment facility. Each patient had different presenting symptoms as well as different ocular manifestations.

Conserving a threatened North American walnut: a chromosome-scale reference genome for butternut (Juglans cinerea).

With the advent of affordable and more accurate third-generation sequencing technologies, and the associated bioinformatic tools, it is now possible to sequence, assemble, and annotate more species of conservation concern than ever before. Juglans cinerea, commonly known as butternut or white walnut, is a member of the walnut family, native to the Eastern United States and Southeastern Canada. The species is currently listed as Endangered on the IUCN Red List due to decline from an invasive fungus known as Ophiognomonia clavigignenti-juglandacearum (Oc-j) that causes butternut canker. Oc-j creates visible sores on the trunks of the tree which essentially starves and slowly kills the tree. Natural resistance to this pathogen is rare. Conserving butternut is of utmost priority due to its critical ecosystem role and cultural significance. As part of an integrated undergraduate and graduate student training program in biodiversity and conservation genomics, the first reference genome for Juglans cinerea is described here. This chromosome-scale 539 Mb assembly was generated from over 100 × coverage of Oxford Nanopore long reads and scaffolded with the Juglans mandshurica genome. Scaffolding with a closely related species oriented and ordered the sequences in a manner more representative of the structure of the genome without altering the sequence. Comparisons with sequenced Juglandaceae revealed high levels of synteny and further supported J. cinerea's recent phylogenetic placement. Comparative assessment of gene family evolution revealed a significant number of contracting families, including several associated with biotic stress response.

Altered histone abundance as a mode of ovotoxicity during 7,12-dimethylbenz[a]anthracene exposure with additive influence of obesity†.

Histones are slowly evolving chromatin components and chromatin remodeling can incorporate histone variants differing from canonical histones as an epigenetic modification. Several identified histone variants are involved with the environmental stress-induced DNA damage response (DDR). Mechanisms of DDR in transcriptionally inactive, prophase-arrested oocytes and epigenetic regulation are under-explored in ovarian toxicology. The study objective was to identify ovarian proteomic and histone modifications induced by DMBA exposure and an influence of obesity. Post-pubertal wildtype (KK.Cg-a/a; lean) and agouti (KK.Cg-Ay/J; obese) female mice, were exposed to either corn oil (control; CT) or DMBA (1 mg/kg) for 7d via intraperitoneal injection (n = 10/treatment). Ovarian proteome analysis (LC-MS/MS) determined that obesity altered 225 proteins (P < 0.05) with histone 3 being the second least abundant (FC = -5.98, P < 0.05). Histone 4 decreased by 3.33-fold, histone variant H3.3 decreased by 3.05-fold, and H1.2, H1.4 and H1.1(alpha) variants increased by 1.59, 1.90 and 2.01-fold, respectively (P < 0.05). DMBA exposure altered 48 proteins in lean mice with no observed alterations in histones or histone variants. In obese mice, DMBA exposure altered 120 proteins and histone 2B abundance increased by 0.30-fold (P < 0.05). In DMBA-exposed mice, obesity altered the abundance of 634 proteins. Histones 4, 3 and 2A type 1-F decreased by 4.03, 3.71, 0.43-fold, respectively, whereas histone variant H1.2 and linker histone, H15 increased by 2.72- and 3.07-fold, respectively (P < 0.05). Thus, DMBA exposure alters histones and histone variants, and responsivity is more pronounced during obesity, potentially altering ovarian transcriptional regulation.

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.

Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4+ memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development.

What is the association between gender and self-perceived health status when controlling for disease-specific conditions? A retrospective data analysis of pre- and post-operative EQ-5D-5L differences in total hip and knee arthroplasty.

BACKGROUND: The self-perceived health status of patients undergoing total hip and knee arthroplasty (THA and TKA) might differ post-operatively due to gender, age, or comorbidities. Patient-reported outcome measures (PROMs) such as the EQ-5D-5L measure the self-perceived health status. This study investigates whether the index score of the EQ-5D-5L is a valid tool for interpreting gender differences in outcomes for patients undergoing THA and TKA. METHODS: Routine and PROM-data of elective primary THA or TKA patients in two German hospitals between 2016 and 2018 were analyzed. Univariate analysis with Pearson's chi-square was conducted to identify control variables for gender. To quantify the association between gender and the EQ-5D-5L dimensions, a cumulative odds ordinal logistic regression with proportional odds was conducted. RESULTS: Two thousand three hundred sixty-eight​​ THA patients (m = 978; f = 1390) and 1629 TKA patients (m = 715; f = 914) were considered. The regression analysis of the individual EQ-5D-5L dimensions showed that female gender was significantly associated with better self-care (THA and TKA) and better post-operative mobility (THA). In contrast, male gender was significantly associated with less pain/discomfort (TKA) and less anxiety/depression (THA) pre-surgery and 3-months post-surgery. CONCLUSION: Our results confirmed that the self-perceived health status improved after surgery. However, due to the different associations of gender to the individual dimensions of the EQ-5D-5L, the weighted index score clouds the comparability between patients with different gender undergoing THA or TKA. Therefore, we argue to use the individual five dimensions for health status analysis, to reveal relevant additional information.

Patients undergoing total hip and knee arthroplasty (THA and TKA) can fill out standardized questionnaires pre- and post-surgery, such as the EQ-5D-5L, to measure the improvement in the self-perceived health status. The EQ-5D-5L includes mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. We do not know whether male and female patients experience the same improvement in the dimensions or whether significant differences exist. Currently, only index scores of the EQ-5D-5L are used for the comparison of pre- and post-operative health status. However, due to the questionnaire's weighted composition, relevant changes in individual dimensions might be easily missed. Thus, we investigated whether significant differences between gender and the EQ-5D-5L dimensions in patients undergoing TKA and TKA are observable. We found that female patients reported significantly better scores in self-care (THA and TKA) and post-operative mobility (THA). In contrast, male gender was significantly associated with less pain/discomfort (TKA) and less anxiety/depression (THA) pre-surgery and 3-months post-surgery. The EQ-5D-5L's weighted index score, however, does not directly represent these differences. Therefore, we argue to use the individual five dimensions for health status analysis, as relevant additional information on improvement over time would otherwise be missed.

Prospective measurement of outcomes and complications of tibial tuberosity advancement using novel mini plates in small breed dogs.

Cranial cruciate ligament (CrCL) disease is a common orthopedic disease in canine patients. Tibial osteotomy procedures for the treatment of cranial cruciate ligament disease in small breed dogs (<15 kg) have previously been limited. A total of 22 client-owned dogs, 26 stifles, with cranial cruciate ligament disease were treated with novel mini-tibial tuberosity advancement plates. The most common intraoperative complications included the need for plate-cage overlap in 7 stifles (26.92%) and screw head fracture in 1 (3.85%). Post-operative complications included tibial tuberosity fracture (3.85%), post-operative medial patella luxation (7.69%), and persistent lameness (7.69%). Of the 26 stifles evaluated in the medium term (>6-12 months) post-operatively, 92.3% had no lameness, with the remaining 7.7% having Grade 1 lameness. A good to excellent clinical outcome was noted in all 26 stifles that underwent TTA with novel mini plates.

Admixture mapping and selection scans identify genomic regions associated with stomatal patterning and disease resistance in hybrid poplars.

Variation in fitness components can be linked in some cases to variation in key traits. Metric traits that lie at the intersection of development, defense, and ecological interactions may be expected to experience environmental selection, informing our understanding of evolutionary and ecological processes. Here, we use quantitative genetic and population genomic methods to investigate disease dynamics in hybrid and non-hybrid populations. We focus our investigation on morphological and ecophysiological traits which inform our understanding of physiology, growth, and defense against a pathogen. In particular, we investigate stomata, microscopic pores on the surface of a leaf that regulate gas exchange during photosynthesis and are sites of entry for various plant pathogens. Stomatal patterning traits were highly predictive of disease risk. Admixture mapping identified a polygenic basis of disease resistance. Candidate genes for stomatal and disease resistance map to the same genomic regions and experienced positive selection. Genes with functions to guard cell homeostasis, the plant immune system, components of constitutive defenses, and growth-related transcription factors were identified. Our results indicate positive selection acted on candidate genes for stomatal patterning and disease resistance, potentially acting in concert to structure their variation in naturally formed backcrossing hybrid populations.

Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age.

Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.

Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress.