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Abstract Precarious employment (PE) is non-standard employment with uncertain and unstable contract duration, low wages, and limited labour protections and rights. Research has associated PE with workers’ poor mental health and well-being; however, this association has been studied primarily using quantitative methods. This qualitative study seeks to examine the mechanisms between PE and mental health in the context of the COVID-19 pandemic in Ontario, Canada. Specifically, it aims to address: (Benach J, Muntaner C. Precarious employment and health: developing a research agenda. J Epidemiol Community Health. 2007;61(4):276.) How do PE and working conditions impact the mental well-being of workers and members of their close families or households?; and (Kreshpaj B, Orellana C, Burström B, Davis L, Hemmingsson T, Johansson G, et al. What is precarious employment? A systematic review of definitions and operationalizations from quantitative and qualitative studies. Scand J Work Environ Health. 2020;46(3):235–47.) How has the COVID-19 pandemic shaped these relationships? Semi-structured interviews were conducted with a sample of 40 individuals aged 25–55 engaged in PE during the first wave of the COVID-19 pandemic or whose employment was terminated due to the pandemic. Results showed that PE amplified mental health symptoms and illnesses for workers and their families. These experiences were described as chronic, where impacts were exerted on precariously employed workers through systemic discrimination and racism, colonialism, workplace hierarchies, and gendered ideologies. PE negatively impacted mental health through emotional stress about employment and income instability, insecurity, and loss; added pressure for households where both partners are engaged in PE; impacted ability to maintain or improve overall health and well-being; and barriers to social connectedness. Overall, this study characterizes multiple dimensions of PE and the consequences they have on the mental health of workers and their families.

Abstract Large uncertainties persist in modeling shallow, low clouds because of many interacting nonlinear processes and multiple cloud‐controlling environmental factors. In addition, sharp changes in behavior occur when environmental thresholds are met. Model studies that follow a traditional approach of exploring the effects of factors “one‐at‐a‐time” are unable to capture interactions between factors. We simulate a stratocumulus cloud based on the Second Dynamics and Chemistry of Marine Stratocumulus field study using a large‐eddy simulation model coupled with a two‐moment cloud microphysics scheme. The simulations are used to train a Gaussian process emulator, which we then use to visualize the relationships between two cloud‐controlling factors and domain‐averaged cloud properties. Only 29 model simulations were required to train the emulators, which then predicted cloud properties at thousands of new combinations of the two factors. Emulator response surfaces of cloud liquid water path and cloud fraction show two behavioral regimes, one of thin and patchy yet steady stratocumulus and one of thick, growing stratocumulus with cloud fraction near 1. Internal variability (initial‐condition uncertainty) creates unrealistic “bumpy” response surfaces. However, we show that the variability causing the bumpiness can be characterized in an emulator “nugget term” that is adjusted to match the distribution of a small number of initial‐condition ensemble simulations at various points on the surface, thereby allowing a smoother, deterministic response surface to be constructed. Accounting for variability allows the transition between regimes, and the joint interactions of parameters, to be visualized in a more deterministic way that has not been done before.

Objectives: Schema Therapy, an approach that integrates cognitive-behavioural and attachment principles, helps us understand the impact of early interactions with caregivers on adult mental health. These early interactions can be assessed through Schema Therapy-informed tools; however, these tools have yet to be used with a postnatal population, which represents a period of vulnerability for new mothers. Therefore, the present study aimed to evaluate the impact of positive and negative early parenting interactions on a first-time mother’s mental health and her sense of competence during the postnatal period, using recently revised and newly developed Schema Therapy-informed tools. Design: This is a cross-sectional study. Method: First-time mothers (N = 220) participated in an online survey within 12 months post-birth. Participants completed the Positive Parenting Schema Inventory (PPSI), Young Parenting Inventory—Revised (YPI-R2), Edinburgh Postnatal Depression Scale (EPDS), and Parenting Sense of Competence (PSOC) scale. The data were analysed using hierarchical multiple regression and mediational analysis. Results: Negative early interactions with mothers and fathers led to greater postnatal depressive symptomology, while positive early interactions with mothers led to fewer postnatal depressive symptoms. Mediation analyses revealed that postnatal depressive symptoms mediated early parenting interactions and participants’ sense of parenting competence as a new mother. Conclusions: The protective effects of positive early interactions with caregivers can help first-time mothers’ postnatal emotional adjustment and their sense of competence through diminished postnatal depressive symptoms. However, the enduring effects of negative early interactions with caregivers can contribute to a first-time mother’s risk of developing postnatal depression and negatively affect her sense of parental competence.

In this tutorial paper, we describe some basic principles and practical considerations for designing probe circuits for NMR or MRI. The goal is building a bridge from material that is familiar from undergraduate physics courses to more specialized information needed to put together and tune a resonant circuit for magnetic resonance. After a brief overview of DC and AC circuits, we discuss the properties of circuit elements used in an NMR probe and how they can be assembled into building blocks for multi-channel circuits. We also discuss the use of transmission lines as circuit elements as well as practical considerations for improving circuit stability and power handling.

Abstract Background Total joint replacement for osteoarthritis is one of the most successful surgical procedures in modern medicine. However, aseptic loosening continues to be a leading cause of revision arthroplasty. The diagnosis of aseptic loosening remains a challenge as patients are often asymptomatic until the late stages. MicroRNA (miRNA) has been demonstrated to be a useful diagnostic tool and has been successfully used in the diagnosis of other diseases. We aimed to identify differentially expressed miRNA in the plasma of patients with aseptic loosening. Methods Adult patients undergoing revision arthroplasty for aseptic loosening and age- and gender-matched controls were recruited. Samples of bone, tissue and blood were collected, and RNA sequencing was performed in 24 patients with aseptic loosening and 26 controls. Differentially expressed miRNA in plasma was matched to differentially expressed mRNA in periprosthetic bone and tissue. Western blot was used to validate protein expression. Results Seven miRNA was differentially expressed in the plasma of patients with osteolysis (logFC >|2|, adj-P |2|, adj-P

Background: To mitigate the spread of Covid-19, nurses infected with the virus were required to isolate themselves from their families and community. Isolated patients were reported to have experienced mental distress, posttraumatic stress disorder symptoms, and suicide. Though studies have reported the psychological impact of the Covid-19 pandemic, less is known about the lived experiences of nurses who survived Covid-19 infection in sub-Saharan Africa. Methods: A descriptive phenomenological approach was used to study the lived experiences of registered nurses who survived Covid-19 disease. In-depth interviews were conducted among nurses diagnosed with Covid-19 from two hospitals in Kenya between March and May, 2021. Purposive and snowball sampling were used to recruit registered nurses. Data were analyzed using Giorgi's steps of analysis. Results: The study included ten nurses between 29 and 45 years of age. Nurses' experiences encompassed three themes: diagnosis reaction, consequences, and coping. Reactions to the diagnosis included fear, anxiety, and sadness. The consequence of the diagnosis and isolation was stigma, isolation, and loneliness. Nurses coping mechanisms included acceptance, creating routines, support, and spirituality. Conclusion: Our findings aid in understanding how nurses experienced Covid-19 infection as patients and will provide evidence-based content for supporting nurses in future pandemics. Moreover, as we acknowledge the heroic contribution of frontline healthcare workers during the Covid-19 pandemic, it is prudent to recognize the considerable occupational risk as they balance their duty to care, and the risk of infection to themselves and their families.

Psychological science increasingly employs virtual reality (VR) as a therapeutic and experimental tool. When represented by an avatar, a user's self-perception is altered through a full-body perceptual illusion known as virtual embodiment. However, inconsistent measurement of this construct derives uncertainties about the efficacy of VR-driven behavioural, cognitive, and social-psychological changes. Accordingly, we sought to provide psychological scientists a valid and reliable measure to assess the virtual embodiment construct during experimental and therapeutic simulations. In a repeated-measures experimental paradigm, participants (N = 86) completed a series of visuo-motor tasks in-vivo and in VR. Our study had three objectives: 1) compare visuo-motor performance across in-vivo and VR tasks; 2) assess the psychometric properties of theoretically foundational body ownership, agency, and self-location dimensions from a virtual embodiment questionnaire widely used in the literature; 3) analyse the simplified 11-item questionnaire's underlying structure using principal component analysis (PCA). We found that VR embodiment does not directly align with physical embodiment when considering proprioception and kinaesthesia, and there is limited support for convergent and discriminant validity of body ownership, agency, and self-location as independent dimensions of the embodiment construct. However, there is strong support for criterion validity when these dimensions comprise the overall measurement of embodiment. The PCA revealed a straightforward and theoretically interpretable underlying structure with three components: embodiment, disembodiment, and agency. This study offers psychometric support for the exploration of the simplified 11-item questionnaire as a theoretically grounded measure for behavioural scientists who seek to investigate virtual embodiment as a psychological construct.

BackgroundAt menstruation, the functional layer of the human endometrium sheds off due to the trigger of the release of inflammatory factors, including interleukin 6 (IL-6), as a result of a sharp decline in progesterone levels, leading to tissue breakdown and bleeding. The endometrial mesenchymal stem-like cells (CD140b+CD146+ eMSC) located in the basalis are responsible for the cyclical regeneration of the endometrium after menstruation. Endometrial cells from the menstruation phase have been proven to secrete a higher amount of IL-6 and further enhance the self-renewal and clonogenic activity of eMSC. However, the IL-6-responsive mechanism remains unknown. Thus, we hypothesized that IL-6 secreted from niche cells during menstruation regulates the proliferation and self-renewal of eMSC through the WNT/β-catenin signaling pathway.MethodsIn this study, the content of IL-6 across the menstrual phases was first evaluated. Coexpression of stem cell markers (CD140b and CD146) with interleukin 6 receptor (IL-6R) was confirmed by immunofluorescent staining. In vitro functional assays were conducted to investigate the effect of IL-6 on the cell activities of eMSC, and the therapeutic role of these IL-6- and WNT5A-pretreated eMSC on the repair of injured endometrium was observed using an established mouse model.ResultsThe endometrial cells secrete a high amount of IL-6 under hypoxic conditions, which mimic the physiological microenvironment in the menstruation phase. Also, the expression of IL-6 receptors was confirmed in our eMSC, indicating their capacity to respond to IL-6 in the microenvironment. Exogenous IL-6 can significantly enhance the self-renewal, proliferation, and migrating capacity of eMSC. Activation of the WNT/β-catenin signaling pathway was observed upon IL-6 treatment, while suppression of the WNT/β-catenin signaling impaired the stimulatory role of IL-6 on eMSC activities. IL-6- and WNT5A-pretreated eMSC showed better performance during the regeneration of the injured mouse endometrium.ConclusionWe demonstrate that the high level of IL-6 produced by endometrial cells at menstruation can induce the stem cells in the human endometrium to proliferate and migrate through the activation of the WNT/β-catenin pathway. Treatment of eMSC with IL-6 and WNT5A might enhance their therapeutic potential in the regeneration of injured endometrium.

We describe an automated hands-off bench testing method for measuring the magnetic field profile of transceiver coils for nuclear magnetic resonance (NMR). The scattering parameter (S-parameter) data is measured using a portable network analyzer, and the results are automatically exported to a computer for plotting and viewing. This assay dramatically reduces the time needed to measure the magnetic field (B1) homogeneity profile of a transceiver coil while also improving accuracy relative to manual operation. Here, we demonstrate the method on a saddle coil of a solution-state NMR probe in comparison to profiles obtained using NMR spectroscopy measurements. We also measure the axial homogeneity of a variable-pitch solenoid.

Abstract During conversations people coordinate simultaneous channels of verbal and nonverbal information to hear and be heard. But the presence of background noise levels such as those found in cafes and restaurants can be a barrier to conversational success. Here, we used speech and motion-tracking to reveal the reciprocal processes people use to communicate in noisy environments. Conversations between twenty-two pairs of typical-hearing adults were elicited under different conditions of background noise, while standing or sitting around a table. With the onset of background noise, pairs rapidly adjusted their interpersonal distance and speech level, with the degree of initial change dependent on noise level and talker configuration. Following this transient phase, pairs settled into a sustaining phase in which reciprocal speech and movement-based coordination processes synergistically maintained effective communication, again with the magnitude of stability of these coordination processes covarying with noise level and talker configuration. Finally, as communication breakdowns increased at high noise levels, pairs exhibited resetting behaviors to help restore communication—decreasing interpersonal distance and/or increasing speech levels in response to communication breakdowns. Approximately 78 dB SPL defined a threshold where behavioral processes were no longer sufficient for maintaining effective conversation and communication breakdowns rapidly increased.

Abstract Background Treatment of brain tumors, epilepsy, or hemodynamic abnormalities requires a craniotomy to access the brain. Nearly 1 million craniotomies are performed in the US annually, which increase to ~ 14 million worldwide and despite prophylaxis, infectious complications after craniotomy range from 1 to 3%. Approximately half are caused by Staphylococcus aureus (S. aureus), which forms a biofilm on the bone flap that is recalcitrant to antibiotics and immune-mediated clearance. However, the mechanisms responsible for the persistence of craniotomy infection remain largely unknown. The current study examined the role of IL-10 in promoting bacterial survival. Methods A mouse model of S. aureus craniotomy infection was used with wild type (WT), IL-10 knockout (KO), and IL-10 conditional KO mice where IL-10 was absent in microglia and monocytes/macrophages (CX3CR1 Cre IL-10 fl/fl ) or neutrophils and granulocytic myeloid-derived suppressor cells (G-MDSCs; Mrp8 Cre IL-10 fl/fl ), the major immune cell populations in the infected brain vs. subcutaneous galea, respectively. Mice were examined at various intervals post-infection to quantify bacterial burden, leukocyte recruitment, and inflammatory mediator production in the brain and galea to assess the role of IL-10 in craniotomy persistence. In addition, the role of G-MDSC-derived IL-10 on neutrophil activity was examined. Results Granulocytes (neutrophils and G-MDSCs) were the major producers of IL-10 during craniotomy infection. Bacterial burden was significantly reduced in IL-10 KO mice in the brain and galea at day 14 post-infection compared to WT animals, concomitant with increased CD4+ and γδ T cell recruitment and cytokine/chemokine production, indicative of a heightened proinflammatory response. S. aureus burden was reduced in Mrp8 Cre IL-10 fl/fl but not CX3CR1 Cre IL-10 fl/fl mice that was reversed following treatment with exogenous IL-10, suggesting that granulocyte-derived IL-10 was important for promoting S. aureus craniotomy infection. This was likely due, in part, to IL-10 production by G-MDSCs that inhibited neutrophil bactericidal activity and TNF production. Conclusion Collectively, these findings reveal a novel role for granulocyte-derived IL-10 in suppressing S. aureus clearance during craniotomy infection, which is one mechanism to account for biofilm persistence.

Abstract Background Aseptic loosening is a leading cause of revision following total hip and knee arthroplasty which is caused by chronic inflammation around the prosthesis. Diabetes mellitus causes systemic inflammatory changes which could increase the risk of aseptic loosening. This study investigated the association between diabetes mellitus and aseptic loosening around hip and knee arthroplasty. Methods A case-control study was conducted at a single arthroplasty centre over the seven-year period of January 2015 to December 2021. Cases were defined as any adult patient undergoing revision hip or knee arthroplasty for aseptic loosening. Controls were randomly selected patients undergoing primary total hip or knee arthroplasty during the same period at a 1:4 ratio. Risk factors were compared between the two groups. Results A total of 440 patients were included in our study – 88 in the aseptic loosening group and 352 patients in the control group. The odds of having diabetes mellitus in the aseptic loosening group was 2.78 (95%CI 1.31–5.92, P = 0.01). Other risk factors were not significantly different between the two groups. Conclusions The incidence of diabetes mellitus is significantly greater in patients undergoing revision arthroplasty for aseptic loosening. Further research is required to explore whether this association is indeed causative.

Abstract This study investigated the utility of supervised machine learning (SML) and explainable artificial intelligence (AI) techniques for modeling and understanding human decision-making during multiagent task performance. Long short-term memory (LSTM) networks were trained to predict the target selection decisions of expert and novice players completing a multiagent herding task. The results revealed that the trained LSTM models could not only accurately predict the target selection decisions of expert and novice players but that these predictions could be made at timescales that preceded a player’s conscious intent. Importantly, the models were also expertise specific, in that models trained to predict the target selection decisions of experts could not accurately predict the target selection decisions of novices (and vice versa). To understand what differentiated expert and novice target selection decisions, we employed the explainable-AI technique, SHapley Additive explanation (SHAP), to identify what informational features (variables) most influenced modelpredictions. The SHAP analysis revealed that experts were more reliant on information about target direction of heading and the location of coherders (i.e., other players) compared to novices. The implications and assumptions underlying the use of SML and explainable-AI techniques for investigating and understanding human decision-making are discussed.

Cataract disease is strongly associated with progressively accumulating oxidative damage to the extremely long-lived crystallin proteins of the lens. Cysteine oxidation affects crystallin folding, interactions, and light-scattering aggregation especially strongly due to the formation of disulfide bridges. Minimizing crystallin aggregation is crucial for lifelong lens transparency, so one might expect the ubiquitous lens crystallin superfamilies (α and βγ) to contain little cysteine. Yet, the Cys content of γ-crystallins is well above the average for human proteins. We review literature relevant to this longstanding puzzle and take advantage of expanding genomic databases and improved machine learning tools for protein structure prediction to investigate it further. We observe remarkably low Cys conservation in the βγ-crystallin superfamily; however, in γ-crystallin, the spatial positioning of Cys residues is clearly fine-tuned by evolution. We propose that the requirements of long-term lens transparency and high lens optical power impose competing evolutionary pressures on lens βγ-crystallins, leading to distinct adaptations: high Cys content in γ-crystallins but low in βB-crystallins. Aquatic species need more powerful lenses than terrestrial ones, which explains the high methionine content of many fish γ- (and even β-) crystallins. Finally, we discuss synergies between sulfur-containing and aromatic residues in crystallins and suggest future experimental directions.

OBJECTIVES/GOALS: Racial discrimination and its associated stress are well-documented contributors to health disparities among African Americans (AA).This feasibility study aimed to acquire methodological insights and build the infrastructure for a subsequent mindfulness interventional study to reduce the effects of racism-based stress. METHODS/STUDY POPULATION: 20 AA participants ( female 12, male 8 )ages 18-50 were enrolled, and clinical data (blood pressure, waist/hip, BMI, lipids, HbA1c, creatinine) for Allostatic Index were collected. Racism-based stress was measured using RBTSSS and the Everyday Discrimination Scale (EDS). Psychometric measures (Coping, resilience, mindfulness, social connection) and sleep (PSQI) were included. Bivariate analysis explored associations between psychological measures and stress biomarkers, supported by Spearman’s correlation analysis. RESULTS/ANTICIPATED RESULTS: Low discrimination (EDS) was associated with a lower Total cholesterol/HDL ratio (2.99 vs. 4.20, p=0.009) and higher HDL (62 vs. 52, p=0.001). Low EDS participants also had better sleep (mean=3, SD=1.33, vs. mean=5.8, SD=3.99, p=0.05*) but reported less coping through drugs and alcohol (p=0.022*) and higher resilience (p=0.047*). Mindfulness negatively correlated to sleep disturbance (r=-0.477 to r=-0.62), coping and resilience. . EDS correlated with overall life stress and drug and alcohol use. Sleep disturbance was negatively associated with social connection (r=-0.569**) and mindfulness. Sleep disturbance and discrimination correlated positively with drug and alcohol use and overall life stress (r=0.52 and r=0.0.59, respectively), while resilience was negatively correlated with sleep (r=-0.45). DISCUSSION/SIGNIFICANCE: Discrimination was associated with increased stress and unfavorable coping, while mindfulness may offer potential benefits for sleep, coping, and resilience. These preliminary findings provide a foundation for further exploring the potential of mindfulness interventions to address the biopsychological impacts of racism-induced stress.

Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique. This review is written for clinicians involved in neuro-oncologic care (nonphysicists) as the target audience explaining what they need to know as CEST makes its way into practice. The purpose of this article is to (1) review the basic physics and technical principles of CEST MRI, and (2) review the practical applications of CEST in neuro-oncology.

Abstract Premise Matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) is a chemical imaging method that can visualize spatial distributions of particular molecules. Plant tissue imaging has so far mostly used cryosectioning, which can be impractical for the preparation of large‐area imaging samples, such as full flower petals. Imaging unsectioned plant tissue presents its own difficulties in extracting metabolites to the surface due to the waxy cuticle. Methods We address this by using established delipidation techniques combined with a solvent vapor extraction prior to applying the matrix with many low‐concentration sprays. Results Using this procedure, we imaged tissue from three different plant species (two flowers and one carnivorous plant leaf). Material factorization analysis of the resulting data reveals a wide range of plant‐specific small molecules with varying degrees of localization to specific portions of the tissue samples, while facilitating detection and removal of signal from background sources. Conclusions This work demonstrates applicability of MALDI‐MSI to press‐dried plant samples without freezing or cryosectioning, setting the stage for spatially resolved molecule identification. Increased mass resolution and inclusion of tandem mass spectrometry are necessary next steps to allow more specific and reliable compound identification.

Abstract Introduction With mobile technologies becoming more advanced and accessible, mobile health (mHealth) has been incorporated in delivering timely and convenient breastfeeding support. However, its feasibility and potential efficacy remain to be examined. Therefore, the primary objective of this study is to assess the feasibility and acceptability of an online instant messaging peer support group for breastfeeding. The secondary objective is to evaluate the effect of the intervention on breastfeeding outcomes. Methods A pilot randomized controlled trial was conducted. A total of 33 primiparous women were recruited in the antenatal clinic at a public hospital in Hong Kong between March and April 2021. They were randomized to receive either standard care (n = 18) or standard care and receive peer-group support in an online instant messaging app (n = 15). Participants received telephone follow-up for up to six months postpartum or until they stopped breastfeeding. After completing the study, six participants in the intervention group were interviewed to understand their perceptions of the intervention. Results This pilot study shows that online messaging peer support group is feasible and acceptable to women. In total, 54.4% of the eligible women agreed to participate, and 97.0% completed the follow-up. Participants perceived that providing peer support through instant messaging app is appropriate. It serves as a channel for the participants to ask questions and obtain information. Furthermore, meetings of the peer supporters and group members can be held to enhance the effectiveness of the intervention. In addition, no significant differences were found in any and exclusive breastfeeding rates, breastfeeding attitude, and breastfeeding self-efficacy between the two groups. Conclusions This study shows that online messaging peer support group is feasible and acceptable. A full-scale study should be conducted to understand the effect of the online instant messaging peer support group on breastfeeding outcomes. Trial Registration: The study protocol is registered on Clinicaltrial.gov (NCT04826796) on 1 April 2021

Notch signaling promotes the quiescent state of endometrial mesenchymal stromal/stem cells (eMSC), whose re-rentry into the cell cycle is in turn influenced by Notch and Wnt signaling from the microenvironment.

Abstract We had previously identified visual impairment increasing risk of incident dementia. While a bi-directional vision-cognition association has subsequently been proposed, no study has specifically examined the longitudinal association between dementia and incidence of clinically defined visual impairment. In this territory-wide community cohort study of 10,806 visually unimpaired older adults, we examined their visual acuity annually for 6 years and tested if dementia at baseline was independently associated with higher risk of incident visual impairment (LogMAR ≥ 0.50 in the better eye despite best correction, which is equivalent to moderate visual impairment according to the World Health Organization definition). By the end of Year 6, a total of 3151 (29.2%) participants developed visual impairment. However, we did not find baseline dementia associating with higher risk of incident visual impairment, after controlling for baseline visual acuity, cataract, glaucoma, diabetes, hypertension, hypercholesterolemia, heart diseases, stroke, Parkinson’s disease, depression, hearing and physical impairments, physical, intellectual and social activities, diet, smoking, age, sex, educational level, and socioeconomic status. Among different covariables, baseline visual acuity appears to be more important than dementia in contributing to the development of visual impairment. Our present findings highlight the need for re-evaluating whether dementia is indeed a risk factor for visual impairment.

IntroductionThe purpose of this retrospective study was to determine the relationship between pretherapy hemoglobin levels and progression-free survival among women with uterine cervix cancer undergoing concurrent weekly cisplatin and radiotherapy followed by brachytherapy.MethodsPatients with advanced-stage II-IVA uterine cervix cancer were grouped by hemoglobin level (Hgb ≥ 12.0, 11.9-10.0, or < 10.0 g/dL). Endpoints were progression-free survival, overall survival, and local control.ResultsBetween 01/2001 and 07/2022, 168 patients contributed demographic, tumor, pretherapy hemoglobin, and outcome data with a median follow-up of 31 months. Progression-free survival at three years was 73% (95% confidence interval: 58%-84%), 71% (95% confidence interval: 56%-82%), and 62% (95% confidence interval: 44%-75%) for the Hgb ≥ 12.0, 11.9-10.0, or < 10.0 g/dL groups, respectfully (P < 0.001). In addition, pretherapy hemoglobin levels were significant with treatment outcome when included in a multivariate analysis of prognostic variables.DiscussionIn conclusion, the difference in pretherapy hemoglobin level was prognostic of progression-free survival.

Abstract During implantation, a symphony of interaction between the trophoblast originated from the trophectoderm of the implanting blastocyst and the endometrium leads to a successful pregnancy. Defective interaction between the trophoblast and endometrium often results in implantation failure, pregnancy loss, and a number of pregnancy complications. Owing to ethical concerns of using in vivo approaches to study human embryo implantation, various in vitro culture models of endometrium were established in the past decade ranging from two-dimensional cell-based to three-dimensional extracellular matrix (ECM)/tissue-based culture systems. Advanced organoid systems have also been established for recapitulation of different cellular components of the maternal–fetal interface, including the endometrial glandular organoids, trophoblast organoids and blastoids. However, there is no single ideal model to study the whole implantation process leaving more research to be done pursuing the establishment of a comprehensive in vitro model that can recapitulate the biology of trophoblast-endometrium interaction during early pregnancy. This would allow us to have better understanding of the physiological and pathological process of trophoblast-endometrium interaction during implantation.

Abstract Humans typically coordinate their muscles to meet movement objectives like minimizing energy expenditure. In the presence of pathology, new objectives gain importance, like reducing loading in an osteoarthritic joint, but people often do not change their muscle coordination patterns to meet these new objectives. Here we use musculoskeletal simulations to identify simple changes in coordination that can be taught using electromyographic biofeedback, achieving the therapeutic goal of reducing joint loading. Our simulations predicted that changing the relative activation of two redundant ankle plantarflexor muscles—the gastrocnemius and soleus—could reduce knee contact force during walking, but it was unclear whether humans could re-coordinate redundant muscles during a complex task like walking. Our experiments showed that after a single session of walking with biofeedback of summary measures of plantarflexor muscle activation, healthy individuals reduced the ratio of gastrocnemius-to-soleus muscle activation by 25 ± 15% (p = 0.004, paired t test, n = 10). Participants who walked with this “gastrocnemius avoidance” gait pattern reduced late-stance knee contact force by 12 ± 12% (p = 0.029, paired t test, n = 8). Simulation-informed coordination retraining could be a promising treatment for knee osteoarthritis and a powerful tool for optimizing coordination for a variety of rehabilitation and performance applications.

Abstract A concealable stigmatised identity (CSI) is any identity that can be hidden but, if revealed, can be potentially socially devaluing (e.g., sexual minority). Those living with a CSI have opportunities to disclose their identities to friends and family members or within professional contexts. According to the disclosure processes model, people adopt either approach-oriented or avoidance-oriented goals when self disclosing. The current study sought to identify how antecedent goals and relationship context are embodied in the dynamics of unintentional behaviours during disclosure. Participants simulated a disclosure event to both close other and professional other targets and were primed with either approach or avoidance-motivations. Postural activity and language were analysed using detrended fluctuation analysis and recurrence quantification analysis. Results revealed that the movement dynamics of participants who were motivated by approach goals exhibited more complex and flexible behaviour compared to those who were motivated by avoidance goals. In addition, there was more recurrent word use towards close others compared to professional others. These results support the supposition of the disclosure processes model that approach-avoidance motivation impacts behaviour and sheds light on the functional differences between relationship contexts on a CSI disclosure experience.

To prevent or mitigate chronic illness burden, people with cystic fibrosis (pwCF) and their family caregivers need primary (generalist-level) palliative care from the time of diagnosis forward. We used qualitative methods to explore their preferences about a screening-and-triage model (“ Improving Life with CF ”) developed to standardize this care. We purposively sampled and interviewed 14 pwCF and caregivers from 5 Improving Life with CF study sites. Thematic analysis was guided by a priori codes using the National Consensus Project's Guidelines for Quality Palliative Care. Participants included 7 adults and 2 adolescents with CF (3 with advanced disease), 4 parents, 1 partner (7 women; 5 people of color). Few were familiar with palliative care. Illness burden was described in multiple domains, including physical (e.g., dyspnea, pain), psychological (e.g., anxiety), and social (e.g., family well-being; impact on work/school). Most preferred survey-based screening with care coordination by the CF team. Preferences for screening approaches varied. PwCF and caregivers experience illness burden and are receptive to a CF-team delivered primary palliative care screening-and-triage model with flexible processes.

Abstract Background Active participation in intellectual leisure activities such as calligraphy helps prevent cognitive decline and dementia, but the underlying mechanisms are not fully understood. With disrupted functional connectivity (FC) of default mode network (DMN) associated with cognitive decline, we speculate that intellectual activities might optimize cognitive function through modulating FC of DMN. This two-arm single-blind randomized controlled trial aims to identify the effects of increasing practice of calligraphy on cognitive function and FC of DMN in people with subjective cognitive decline (SCD). Methods One hundred twelve community-living Chinese aged 55 to 75 years old with SCD but without mild cognitive impairment or dementia and with prior practice of calligraphy as defined by 1 h of calligraphy per week will be recruited through elderly social centres in Hong Kong and randomized into either control or intervention group. The control group will continue with their usual practice of calligraphy, whereas the intervention group will double their practice of calligraphy. Measurement of cognitive outcomes and neuroimaging on resting-state FC will be performed at baseline and in 6 months. Repeated measures analysis of variance will be used to assess cognitive and FC changes, with time being the within-group factor, control/intervention as the between-group measure, and important covariates (age, sex, educational and occupational attainment, health, and other lifestyle factors) controlled for. Discussion This study will shed light on the underlying neurocognitive mechanisms of how intellectual activities promotes cognitive maintenance. Our anticipated findings will provide evidence that reversing or slowing FC disruption by actively participating in intellectual activities is still possible for the at-risk individuals. Trial registration Chinese Clinical Trial Registry ChiCTR1900024433 . Registered on 11 July 2019.

Cystic fibrosis (CF) lung disease begins early in childhood and is characterized by neutrophilic inflammation of the airways. Neutrophil extracellular traps (NETs) represent one mechanism by which neutrophils contribute to lung damage. The enzyme peptidylarginine deiminase 4 (PAD4) is required for NET formation. Our overall concept is that NET formation delivers PAD4 outside the neutrophil resulting in autoantibody generation, and this autoimmunity may be a novel mechanism contributing to CF lung disease progression. The aim of this study was to investigate clinical predictors of serum anti-PAD4 autoantibody (PAD4 Ab) levels in CF subjects with a wide range of ages from early childhood through middle age. We measured PAD4 Ab levels in sera from 104 CF subjects. PAD4 Abs were detectable among CF children as young as one year of age and elevated compared to paediatric healthy controls. PAD4 Ab levels increased significantly with age (r = 0.584, p

Abstract Objective To evaluate the psychometric properties of the traditional Chinese version of the Childbirth Experience Questionnaire (CEQ 2.0) and assess the childbirth experiences of Chinese women. Methods A cross-sectional survey was conducted in Hong Kong from July 2020 to February 2021. In total, 975 mothers, who could read traditional Chinese and gave birth in 2020 or 2021, were included in the analysis. Data were fitted into the model proposed by the original developers using the confirmatory factor analysis. The data were then randomly split into training and validation sets for exploratory and confirmatory factor analyses. Childbirth experiences were assessed. Factor structure, internal construct validity, internal consistency, and known-group validity were assessed. Results The originally proposed CEQ2.0 model showed a poor fit. An exploratory factor analysis identified a revised four-factor model (CEQ2.0-R) on a randomly split sample, which showed a satisfactory fit (CFI=0.912; TLI=0.884; SRMR=.053; RMSEA=0.072) on the other split sample. The revised scale comprised 13 items and four domains: (1)“Own capacity” (6 items), (2) “General support” (3 items), (3) “Perceived safety” (2 items), and (4) “Professional support” (2 items). CEQ2.0-R showed high internal construct validity and reliability. It can differentiate between participants with different characteristics, including parity, oxytocin augmentation, and companionship during labour. The childbirth experiences of the participants were merely positive, and participants reported that more support from midwives is needed. Conclusions CEQ2.0-R can adequately describe the childbirth experiences of women in Hong Kong. The questionnaire is easy to be administer and can be used to assess several domains of the childbirth experiences. It may be useful to evaluate the aspects of support needed during childbirth.

Purpose: To analyze the 5-year results of accelerated corneal collagen crosslinking (CXL) for progressive keratoconus and identify preoperative characteristics predictive of visual and topographic outcomes. Methods: A prospective interventional case series. Nineteen eyes of 19 patients receiving accelerated CXL with settings of 18 mW/cm2 for 5 min were included. Clinical and topographic parameters were assessed. Linear regression and logistic regression were used to compare the R2 and odds ratio (OR), respectively, between baseline characteristics and postoperative outcomes. Results: Corrected distance visual acuity (CDVA) remained stable from 0.28 ± 0.21 to 0.25 ± 0.18 logMAR (P = 0.486). The mean cylindrical refraction was stable (P = 0.119). The maximal keratometry (Kmax) decreased from 61.99 ± 10.37 to 59.25 ± 7.75 D (P < 0.001), flattening in the flattest and steepest meridians and mean keratometry were also observed (P ≤ 0.040). The mean anterior elevation at the apex reduced from 21.42 ± 16.69 to 18.53 ± 12.74 μm (P = 0.013) and changes in posterior elevation were non-significant (P = 0.629). Preoperative Kmax best predicted the postoperative change in Kmax (R2 = 0.55, P < 0.001) compared to the other baseline characteristics (P ≤ 0.028), whereas preoperative CDVA was the only significant predictor of postoperative change in CDVA (R2 = 0.41, P = 0.003). Accelerated CXL is less likely to fail in eyes with a steeper preoperative Kmax (OR = 0.74, P = 0.040) or greater posterior elevation at the apex (OR = 0.91, P = 0.042). Conclusion: Kmax significantly decreased following accelerated CXL. Eyes with worse preoperative CDVA and higher Kmax were more likely to have an improvement in visual acuity and corneal flattening.

Sex hormones can affect cellular physiology and modulate synaptic plasticity, but it is not always clear whether or how sex-dependent differences identified in vitro express themselves as functional dimorphisms in the brain. Historically, most experimental neuroscience has been conducted using only male animals and the literature is largely mute about whether including female mice in will introduce variability due to inherent sex differences or endogenous estrous cycles. Though this is beginning to change following an NIH directive that sex should be included as a factor in vertebrate research, the lack of information raises practical issues around how to design experimental controls and apply existing knowledge to more heterogeneous populations. Various lines of research suggest that visual processing can be affected by sex and estrous cycle stage. For these reasons, we performed a series of in vivo electrophysiological experiments to characterize baseline visual function and experience-dependent plasticity in the primary visual cortex (V1) of male and female mice. We find that sex and estrous stage have no statistically significant effect on baseline acuity measurements, but that both sex and estrous stage have can modulate two mechanistically distinct forms of experience dependent cortical plasticity. We also demonstrate that resulting variability can be largely controlled with appropriate normalizations. These findings suggest that V1 plasticity can be used for mechanistic studies focusing on how sex hormones effect experience dependent plasticity in the mammalian cortex.

IntroductionHigh-risk human epidermal growth factor receptor 2 (HER2)-positive adenocarcinomas associate with early recurrence and death, prompting consideration of novel radiotherapeutic options like a trastuzumab-linked thorium-227 alpha-particle emitting radionuclide.MethodsWe conducted a retrospective pilot biomarker study of uterine cervix cancers among patients in Appalachian Kentucky, to characterize an exploitable triage biomarker like HER2 expression before starting a prospective phase 0 trial.ResultsMost (60%) adenocarcinomas showed HER2 cell-surface overexpression, whereas squamous cell carcinomas (4%) did not do so.DiscussionFurther validation tests of HER2 expression as a triage biomarker for radiopharmaceutical selection are warranted.

Abstract Background Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use. Methods We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated. Results When prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact. Conclusions All modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.

Abstract. Objectives: Although 3-dimensional (3D) printing is becoming more widely adopted for clinical applications, it is yet to be accepted as part of standard practice. One of the key applications of this technology is orthopaedic surgical planning for urgent trauma cases. Anatomically accurate replicas of patients' fracture models can be produced to guide intervention. These high-quality models facilitate the design and printing of patient-specific implants and surgical devices. Therefore, a fast and accurate workflow will help orthopaedic surgeons to generate high-quality 3D printable models of complex fractures. Currently, there is a lack of access to an uncomplicated and inexpensive workflow. Methods: Using patient DICOM data sets (n = 13), we devised a novel, simple, open-source, and rapid modeling process using Drishti software and compared its efficacy and data storage with the 3D Slicer image computing platform. We imported the computed tomography image directory acquired from patients into the software to isolate the model of bone surface from surrounding soft tissue using the minimum functions. One pelvic fracture case was further integrated into the customized implant design practice to demonstrate the compatibility of the 3D models generated from Drishti. Results: The data sizes of the generated 3D models and the processing files that represent the original DICOM of Drishti are on average 27% and 12% smaller than that of 3D Slicer, respectively (both P < 0.05). The time frame needed to reach the stage of viewing the 3D bone model and the exporting of the data of Drishti is 39% and 38% faster than that of 3D Slicer, respectively (both P < 0.05). We also constructed a virtual model using third-party software to trial the implant design. Conclusions: Drishti is more suitable for urgent trauma cases that require fast and efficient 3D bone reconstruction with less hardware requirement. 3D Slicer performs better at quantitative preoperative planning and multilayer segmentation. Both software platforms are compatible with third-party programs used to produce customized implants that could be useful for surgical training. Level of Evidence: Level V.

The placenta is important for fetal development in mammals, and spatial transcriptomic profiling of placenta helps to resolve its structure and function. In this study, we described the landscape of spatial transcriptome of human placental villi obtained from two pregnant women at the first trimester using the modified Stereo-seq method applied for paraformaldehyde (PFA) fixation samples. The PFA fixation of human placenta villi was better than fresh villi embedded in optimum cutting temperature (OCT) compound, since it greatly improved tissue morphology and the specificity of RNA signals. The main cell types in chorionic villi such as syncytiotrophoblasts (SCT), villous cytotrophoblasts (VCT), fibroblasts (FB), and extravillous trophoblasts (EVT) were identified with the spatial transcriptome data, whereas the minor cell types of Hofbauer cells (HB) and endothelial cells (Endo) were spatially located by deconvolution of scRNA-seq data. We demonstrated that the Stereo-seq data of human villi could be used for sophisticated analyses such as spatial cell-communication and regulatory activity. We found that the SCT and VCT exhibited the most ligand-receptor pairs that could increase differentiation of the SCT, and that the spatial localization of specific regulons in different cell types was associated with the pathways related to hormones transport and secretion, regulation of mitotic cell cycle, and nutrient transport pathway in SCT. In EVT, regulatory pathways such as the epithelial to mesenchyme transition, epithelial development and differentiation, and extracellular matrix organization were identified. Finally, viral receptors and drug transporters were identified in villi according to the pathway analysis, which could help to explain the vertical transmission of several infectious diseases and drug metabolism efficacy. Our study provides a valuable resource for further investigation of the placenta development, physiology and pathology in a spatial context.

Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber disorders, such as pelvic organ prolapse, a phenotype associated with exfoliation syndrome (XFS) in humans. Patients with XFS have a significant risk of developing exfoliation glaucoma (XFG), a severe form of glaucoma, which is a neurodegenerative condition leading to irreversible blindness if not detected and treated in a timely fashion. Although Loxl1−/− mice have been used extensively to investigate mechanisms of pelvic organ prolapse, studies of eyes in those mice are limited and some showed inconsistent ocular phenotypes. In this study we demonstrate that Loxl1−/− mice have significant anterior segment biometric abnormalities which recapitulate some human XFS features. We then focused on the peripapillary sclera (PPS), a critical structure for maintaining optic nerve health. We discovered quantitative and qualitive changes in ultrastructure of PPS, such as reduced elastic fibers, enlarged collagen fibrils, and transformed collagen lamella organization detected by transmission electron microscopy (TEM). Importantly, these changes corelate with altered tissue biomechanics detected by Atomic Force Microscopy (AFM) of PPS in mice. Together, our results support a crucial role for LOXL1 in ocular tissue structure and biomechanics, and Loxl1−/− mice could be a valuable resource for understanding the role of scleral tissue biomechanics in ocular disease.

Plain English Summary Living in a food-insufficient household may increase risk for binge eating and obesity. Because we know very little about this relationship in Black Americans, we conducted a research study to examine the rates of food insufficiency, binge eating, and obesity in a sample of African Americans and Afro-Caribbeans. The prevalence of food insufficiency in the entire sample was 10.9%. In Afro-Caribbeans, individuals with food insufficiency were more likely to have obesity, than those who were food sufficient. We did not see this relationship in African Americans. Individuals with food insufficiency were more likely to report recurrent binge eating in the last 12 months, compared to those with food sufficiency. After adjusting for socio-demographic factors, however, food insufficiency was not significantly associated with recurrent binge eating.

PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG) radiotherapy on the 1.5 T MR-Linac (MRL), with a focus on the temporal variations of the tumor and feasibility of multi-parametric image (mpMRI) acquisition during routine treatment workflow.Materials and methodsTen HGG patients treated with radiation within the first year of the MRL’s clinical operation, between October 2019 and August 2020, were identified from a prospective database. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the relative FHR volumes (n = 281 contours) and migration distances (maximum linear displacement of the volume). Research mpMRIs were acquired on the MRL during radiation and changes in selected functional parameters were investigated within the FHR.ResultsAll patients completed radiotherapy to a median dose of 60 Gy (range, 54-60 Gy) in 30 fractions (range, 30-33), receiving a total of 287 fractions on the MRL. The mean in-room time per fraction with or without post-beam research imaging was 42.9 minutes (range, 25.0–69.0 minutes) and 37.3 minutes (range, 24.0–51.0 minutes), respectively. Three patients (30%) required re-planning between fractions 9 to 12 due to progression of tumor and/or edema identified on daily MRL imaging. At the 10, 20, and 30-day post-first fraction time points 3, 3, and 4 patients, respectively, had a FHR volume that changed by at least 20% relative to the first fraction. Research mpMRIs were successfully acquired on the MRL. The median apparent diffusion coefficient (ADC) within the FHR and the volumes of FLAIR were significantly correlated when data from all patients and time points were pooled (R=0.68, p

Despite the challenges associated with virtually mediated communication, remote collaboration is a defining characteristic of online multiplayer gaming communities. Inspired by the teamwork exhibited by players in first-person shooter games, this study investigated the verbal and behavioral coordination of four-player teams playing a cooperative online video game. The game, Desert Herding, involved teams consisting of three ground players and one drone operator tasked to locate, corral, and contain evasive robot agents scattered across a large desert environment. Ground players could move throughout the environment, while the drone operator’s role was akin to that of a “spectator” with a bird’s-eye view, with access to veridical information of the locations of teammates and the to-be-corralled agents. Categorical recurrence quantification analysis (catRQA) was used to measure the communication dynamics of teams as they completed the task. Demands on coordination were manipulated by varying the ground players’ ability to observe the environment with the use of game “fog.” Results show that catRQA was sensitive to changes to task visibility, with reductions in task visibility reorganizing how participants conversed during the game to maintain team situation awareness. The results are discussed in the context of future work that can address how team coordination can be augmented with the inclusion of artificial agents, as synthetic teammates.

The broad activity of agents blocking the programmed cell death protein 1 and its ligand (the PD-(L)1 axis) revolutionized oncology, offering long-term benefit to patients and even curative responses for tumors that were once associated with dismal prognosis. However, only a minority of patients experience durable clinical benefit with immune checkpoint inhibitor monotherapy in most disease settings. Spurred by preclinical and correlative studies to understand mechanisms of non-response to the PD-(L)1 antagonists and by combination studies in animal tumor models, many drug development programs were designed to combine anti-PD-(L)1 with a variety of approved and investigational chemotherapies, tumor-targeted therapies, antiangiogenic therapies, and other immunotherapies. Several immunotherapy combinations improved survival outcomes in a variety of indications including melanoma, lung, kidney, and liver cancer, among others. This immunotherapy renaissance, however, has led to many combinations being advanced to late-stage development without definitive predictive biomarkers, limited phase I and phase II data, or clinical trial designs that are not optimized for demonstrating the unique attributes of immune-related antitumor activity—for example, landmark progression-free survival and overall survival. The decision to activate a study at an individual site is investigator-driven, and generalized frameworks to evaluate the potential for phase III trials in immuno-oncology to yield positive data, particularly to increase the number of curative responses or otherwise advance the field have thus far been lacking. To assist in evaluating the potential value to patients and the immunotherapy field of phase III trials, the Society for Immunotherapy of Cancer (SITC) has developed a checklist for investigators, described in this manuscript. Although the checklist focuses on anti-PD-(L)1-based combinations, it may be applied to any regimen in which immune modulation is an important component of the antitumor effect.

BackgroundThe COVID-19 pandemic has imposed a profound negative impact on the mental health and wellbeing of societies and individuals worldwide. Older adults may be more vulnerable to the mental health effects of the pandemic, either directly from the infection itself or indirectly through the preventive measures. However, the existing literature on mental health in the older age groups has not been consistent so far. The aim of this study was therefore to assess the prevalence of common mental disorders (CMD; including depression and anxiety disorders) given their association with dementia risk, and to further examine age-related differences between older (≥60 years old) and younger (18–59 years old) adult's psychological status during the COVID-19 pandemic.MethodThis was a secondary analysis of a cross-sectional survey-study conducted during the second wave of COVID-19 pandemic in Hong Kong. The survey was disseminated through different social media platforms to the general population and included sociodemographic questions, self-reported physical health, and previous encounter with SARS or COVID-19. CMD was the primary outcome and was assessed using the 6-item Kessler Scale. A total of 1030 adults fulfilled inclusion criteria.ResultsThe prevalence of CMD during the pandemic was 16.1%. Compared to younger adults, older adults were significantly less likely to have a CMD (unadjusted OR = 0.07, 95% CI = 0.02–0.30, p < 0.001), with 18.1% of younger adults having CMD compared to 1.6% in the older cohort. Age differences remained significant after controlling for sociodemographic factors, physical health, and previous encounter with SARS or COVID-19 (adjusted OR = 0.12, 95% CI = 0.02–0.57, p = 0.008).ConclusionCommon mental disorders are highly prevalent during the COVID-19 pandemic in Hong Kong, though older adults appeared to be less affected mentally. Present findings highlight the urgent need to implement measures and strategies to mitigate the mental health problems, with particular attention to the younger cohort. Given their association with higher dementia risk, early detection and treatment of depression and anxiety disorders will be of critical importance in providing some relief to the already pressurized dementia burden in the longer term.

Although mutations in ADAMTS10 have long been known to cause autosomal recessive Weill-Marchesani Syndrome which is characterized by short stature and ocular abnormalities, more recent work has shown that certain mutations in ADAMTS10 cause glaucoma in dogs. In humans, glaucoma is the leading cause of irreversible vision loss that affects tens of millions of people world-wide. Vision loss in glaucoma is a result of neurodegeneration of retinal ganglion cells that form the inner-most layer of the retina and whose axons form the optic nerve which relays visual information to the brain. ADAMTS10 contributes to the formation of microfibrils which sequester latent transforming growth factor β (TGFβ). Among its many biological functions, TGFβ promotes the development of retinal ganglion cells and is also known to play other roles in glaucoma pathogenesis. The aim of this study was to test the hypothesis that ADAMTS10 plays a role in retinal ganglion cell development through regulation of TGFβ signaling. To this end, Adamts10 expression was targeted for reduction in zebrafish embryos carrying either a fluorescent reporter that labels retinal ganglion cells, or a fluorescent reporter of pSmad3-mediated TGFβ family signaling. Loss of adamts10 function in zebrafish embryos reduced retinal ganglion cell reporter fluorescence and prevented formation of an ordered retinal ganglion cell layer. Targeting adamts10 expression also drastically reduced constitutive TGFβ signaling in the eye. Direct inhibition of the TGFβ receptor reduced retinal ganglion cell reporter fluorescence similar to the effect of targeting adamts10 expression. These findings unveil a previously unknown role for Adamts10 in retinal ganglion cell development and suggest that the developmental role of Adamts10 is mediated by active TGFβ family signaling. In addition, our results show for the first time that Adamts10 is necessary for pSmad3-mediated constitutive TGFβ family signaling.

Abstract Background HIV clinical care programs in high burden settings are uniquely positioned to facilitate diabetes diagnosis, which is a major challenge. However, in sub-Saharan Africa, data on the burden of diabetes among people living with HIV (PLHIV) and its impact on HIV outcomes is sparse. Methods We enrolled adults presenting for HIV testing at an outpatient clinic in Durban. Those who tested positive for HIV-infection were screened for diabetes using a point-of-care hemoglobin A1c (HbA1c) test. We used log-binomial, Poisson, and Cox proportional hazard models adjusting for confounders to estimate the relationship of diabetes (HbA1c ≥ 6.5%) with the outcomes of HIV viral suppression (

Abstract Background Diabetes and hypertension are increasingly prevalent in low and middle income countries, but they are not well documented in refugee settlements in these settings. We sought to estimate the prevalence and associated characteristics of diabetes and hypertension among adults presenting for clinic-based HIV testing in Nakivale Refugee Settlement in Uganda. Methods HIV-negative adults presenting to outpatient clinics for HIV testing at three health centers in Nakivale Refugee Settlement were enrolled from January 2019 through January 2020. Multi-lingual research assistants administered questionnaires aloud to ascertain medical history and sociodemographic information. The research assistants used standardized procedures to measure participants’ blood pressure to detect hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), and conduct a point-of-care blood glucose test for diabetes (random blood glucose ≥11.1 mmol/L with self-reported frequent urination or thirst, or fasting blood glucose ≥7.0 mmol/L regardless of symptoms), as per Uganda Ministry of Health guidelines. We used χ-square or Fisher’s exact test to test for differences in disease prevalence by refugee status and log-binomial or Poisson regression models to estimate associations of immigration status and country of origin, respectively, with hypertension and diabetes while controlling for age, sex, education level, and body mass index. Results Among 2127 participants, 1379 (65%) were refugees or asylum seekers and 748 (35%) were Ugandan nationals. Overall, 32 participants met criteria for diabetes (1.5%, 95% CI 1.1–2.1%) and the period prevalence was 2.3% (95% CI 1.7–3.0). There were 1067 (50%, 95% CI 48.0–52.2%) who met the criteria for pre-hypertension and 189 (9%, 95% CI 7.7–10.1%) for hypertension. These proportions did not vary by immigration status or country of origin in univariate tests or multivariable regression models. Conclusions Hypertension was common and diabetes was uncommon among those screened in a Ugandan refugee settlement. Routine blood pressure screening should be considered in this setting. Additional research could develop diabetes screening criteria to help identify at risk individuals in this limited resource setting.

People can infer unobserved causes of perceptual data (e.g. the contents of a box from the sound made by shaking it). Here the authors show that children compare what they hear with what they would have heard given other causes, and explore longer when the heard and imagined sounds are hard to discriminate.

Abstract Background Endometrial mesenchymal-like stromal/stem cells (eMSCs) have been proposed as adult stem cells contributing to endometrial regeneration. One set of perivascular markers (CD140b&CD146) has been widely used to enrich eMSCs. Although eMSCs are easily accessible for regenerative medicine and have long been studied, their cellular heterogeneity, relationship to primary counterpart, remains largely unclear. Methods In this study, we applied 10X genomics single-cell RNA sequencing (scRNA-seq) to cultured human CD140b+CD146+ endometrial perivascular cells (ePCs) from menstrual and secretory endometrium. We also analyzed publicly available scRNA-seq data of primary endometrium and performed transcriptome comparison between cultured ePCs and primary ePCs at single-cell level. Results Transcriptomic expression-based clustering revealed limited heterogeneity within cultured menstrual and secretory ePCs. A main subpopulation and a small stress-induced subpopulation were identified in secretory and menstrual ePCs. Cell identity analysis demonstrated the similar cellular composition in secretory and menstrual ePCs. Marker gene expression analysis showed that the main subpopulations identified from cultured secretory and menstrual ePCs simultaneously expressed genes marking mesenchymal stem cell (MSC), perivascular cell, smooth muscle cell, and stromal fibroblast. GO enrichment analysis revealed that genes upregulated in the main subpopulation enriched in actin filament organization, cellular division, etc., while genes upregulated in the small subpopulation enriched in extracellular matrix disassembly, stress response, etc. By comparing subpopulations of cultured ePCs to the publicly available primary endometrial cells, it was found that the main subpopulation identified from cultured ePCs was culture-unique which was unlike primary ePCs or primary endometrial stromal fibroblast cells. Conclusion In summary, these data for the first time provides a single-cell atlas of the cultured human CD140b+CD146+ ePCs. The identification of culture-unique relatively homogenous cell population of CD140b+CD146+ ePCs underscores the importance of in vivo microenvironment in maintaining cellular identity.

Abstract Background Clinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions. Methods The proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins. Results The recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease. Conclusions The proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies.

Measurement(s) temperature of water • dioxygen dissolved in marine water • salinity of water • water clarity • concentration of ammonium in water • concentration of nitrate plus nitrite in water • concentration of phosphate in water • concentration of nitrogen atom in water • concentration of particulate organic carbon in water • concentration of total phosphorus in water • concentration of dissolved organic carbon in water • chlorophyll a • pheophytin a • concentration of particulate nitrogen in water Technology Type(s) Thermometer Device • titration • hydrometer • Secchi disk • spectrophotometry • chemical digestion followed by spectrophotometry • carbon, hydrogen and nitrogen elemental analysis • catalytic and persulphate oxidation • fluorometry Factor Type(s) year of data collection Sample Characteristic - Environment coastal sea water • bay • estuary Sample Characteristic - Location Buzzards Bay Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13363436

Although extracellular host DNA (ecDNA) levels in CF airways were linked to airflow obstruction and recombinant DNAse therapy is beneficial for CF patients, it remains incompletely understood whether ecDNA also leads to an autoimmune response. Here we hypothesized that chronic presence of DNA in CF airways triggers the production of autoantibodies targeting host human DNA. We measured the levels of IgA autoantibodies recognising host double-stranded (ds) DNA in the blood and sputum samples of CF patients and only sera of controls subjects and patients suffering from rheumatoid arthritis and systemic lupus erythematosus (SLE) that served as non-CF, autoimmune disease cohorts. We found that concentrations of anti-dsDNA IgA, but not IgG, autoantibodies in the circulation were significantly elevated in adult CF patients compared to age-matched, control subjects. Systemic levels of anti-dsDNA IgA antibodies negatively correlated with FEV1% predicted, a measure of lung function, in CF patients. Anti-dsDNA IgA autoantibodies were also detected in CF sputa but sputum levels did not correlate with the degree of airway obstruction or sputum levels of DNA. We also found elevated autoantibody levels in CF children as 76.5% of CF patients younger than 10 years and 87.5% of CF patients 10–21 years had higher blood anti-dsDNA IgA levels than the highest value found in healthy control adults. Overall, our results detect elevated systemic anti-dsDNA IgA autoantibody levels in CF adults, teenagers and young children. We speculate that the appearance of an autoimmune response against host DNA in CF is an early event potentially contributing to disease pathogenesis.Highlights CF serum contains elevated levels of anti-dsDNA IgA, but not anti-dsDNA IgG, autoantibodies Anti-dsDNA IgA autoantibody levels in serum correlate with airflow obstruction in CF Anti-dsDNA IgA autoantibodies are detected in CF sputum but do not correlate with airflow obstruction Anti-dsDNA IgA autoantibodies are also elevated in the blood of the majority of CF toddlers and youth

Abstract Patient-specific surgical guides are increasingly demanded. Material Extrusion (ME) is a popular 3D printing technique to fabricate personalized surgical guides. However, the ME process usually generates deleterious surface topography which is not suitable for orthopaedic emergencies. We designed and optimized parametric combinations of a laser polishing approach as post process to improve the surface quality of ME-made poly-lactic acid (PLA) objects. In this study, we investigated the contribution of processing variables to the mechanical properties and the biocompatibilities in vitro of the ME-made PLA objects. Conventional surface grinding was conducted as comparison. The results demonstrate that the ME-made PLA samples exhibit good mechanical properties and favourable biocompatibility after being post processed using laser polishing. The post laser polishing, as a powerful tool in manufacture of ME-made PLA objects, will open a new approach with a great promise in its applications in personalized and timely management of medical emergencies.

Abstract Background Tuberculosis (TB)-related stigma presents a major barrier to care of persons with TB through its impact on treatment initiation and retention in care. This is particularly challenging in settings with high prevalence of both TB and HIV where fear of HIV/AIDS can amplify stigma surrounding TB. The purpose of this study was to validate a TB stigma scale for use among persons presenting for outpatient HIV screening in the Umlazi township of South Africa and evaluate factors associated with TB-related stigma in this high HIV burden setting. Methods In this cross-sectional study, we measured TB-related stigma in adults prior to HIV testing using a 12-item scale designed to assess experienced and felt TB-related stigma. Results Among 848 adults, mean age was 32 years, 54% were male, and the median TB stigma score was 19 of 36 (interquartile range 15–23). We identified two factors in the stigma scale which had excellent reliability (Cronbach’s alpha 0.85, 0.89). Persons with high TB stigma were more likely to be male (adjusted relative risk ratio [aRRR] 1.56, 95% confidence interval [CI] 1.11–2.28) and have accurate knowledge of TB transmission (aRRR 1.90, 95% CI 1.16–3.10) as compared to those with low stigma. Variables not significantly associated with stigma in the multivariate model included education, income, prior TB or HIV diagnoses, and depression. Conclusions Male sex and TB knowledge were associated with higher TB stigma in an outpatient HIV clinic in a South African township. Identifying risk factors associated with stigma will be important to guide stigma reduction interventions.