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Bleeding in spine surgery is a common occurrence but when bleeding is uncontrolled the consequences can be severe due to the potential for spinal cord compression and damage to the central nervous system. There are many factors that influence bleeding during spine surgery including patient factors and those related to the type of surgery and the surgical approach to bleeding. There are a range of methods that can be employed to both reduce the risk of bleeding and achieve hemostasis, one of which is the adjunct use of hemostatic agents. Hemostatic agents are available in a variety of forms and materials and with considerable variation in cost, but specific evidence to support their use in spine surgery is sparse. A literature review was conducted to identify the pre-, peri-, and postsurgical considerations around bleeding in spine surgery. The review generated a set of recommendations that were discussed and ratified by a wider expert group of spine surgeons. The results are intended to provide a practical guide to the selection of hemostats for specific bleeding situations that may be encountered in spine surgery.

There is a growing interest in the inverse approach to material deign, in which the desired target properties are used as input to identify the atomic identity, composition and structure (ACS) that exhibit such properties. As an overview, this paper surveys and summarizes previous works in metaheuristic-based inverse design of various materials. The basics of metaheuristic-based inverse design of materials are presented, including feature identification (fingerprinting), machine learning of ACS→property models (forward design), metaheuristic algorithms for property→ACS predictions (inverse design), and experimental validations, with focus on inverse design. The past studies are organized into a two-level hierarchy with how properties are predicted at the higher level, either by first principles, simulation, or machine learning model, and the number of target properties considered at the lower level, either one or more than one. The uniqueness and limitation of previous research are discussed and several possible topics for future research are identified. This review intends to serve as the steppingstone/springboard for those interested in advancing this area of research. Keywords: Inverse design, Materials, Metaheuristics, Machine learning, Fingerprinting

Abstract Controlling the formation and growth of ice is essential to successfully cryopreserve cells, tissues and biologics. Current efforts to identify materials capable of modulating ice growth are guided by iterative changes and human intuition, with a major focus on proteins and polymers. With limited data, the discovery pipeline is constrained by a poor understanding of the mechanisms and the underlying structure-activity relationships. In this work, this barrier is overcome by constructing machine learning models capable of predicting the ice recrystallisation inhibition activity of small molecules. We generate a new dataset via experimental measurements of ice growth, then harness predictive models combining state-of-the-art descriptors with domain-specific features derived from molecular simulations. The models accurately identify potent small molecule ice recrystallisation inhibitors within a commercial compound library. Identified hits can also mitigate cellular damage during transient warming events in cryopreserved red blood cells, demonstrating how data-driven approaches can be used to discover innovative cryoprotectants and enable next-generation cryopreservation solutions for the cold chain.

The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 (Δ WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection.In this study, the Δ WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and Δ WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged Δ WD but not wild-type mice. In summary, the LAP-deficient Δ WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.

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Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE, impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE-mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.

The regulation and direction of CD4+ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4+ cytotoxic and T follicular helper lineages.

The COVID-19 pandemic and related school disruptions have led to increased concerns for the mental health of teachers. This study investigated how the challenges and systemic supports perceived by teachers during the COVID-19 pandemic were associated with their mental health and workplace well-being. This cross-sectional, survey-based study was conducted in February 2021, just prior to the third wave of the pandemic in British Columbia (BC), Canada (N = 1,276). Four multivariable linear regression models examined the associations between teachers’ pandemic-related challenges (pandemic-related personal stressors, teacher workload, difficulty implementing safety measures, meeting students’ needs), systemic supports (education system mental health and well-being support), and four mental health (psychological distress, and quality of life) and workplace well-being outcomes (job-related positive affect, turnover intentions), adjusting for sociodemographic and school characteristics. The Pratt index (d) was used to assess the relative importance of each predictor. A thematic qualitative analysis was conducted on teachers’ open-ended responses. Teachers’ workplace well-being (job-related positive affect and turnover intentions) was predominantly associated with their perceptions of education system support for their mental health and well-being (d = 46%, d = 41%, respectively). The most important predictor of general mental health (psychological distress and quality of life) was the number of COVID-19 related personal stressors teachers reported (d = 64%, d = 43%, respectively). The qualitative analyses corroborated and expanded upon the quantitative findings. Understanding pandemic-related challenges and supports impacting teacher mental health and workplace well-being equips us to make evidence-informed policy decisions to support teachers now and in future school disruptions.

Abstract Background Fragile X syndrome is characterized by a myriad of physical features, behavioral features, and medical problems. Commonly found behavioral features are hyperactivity, anxiety, socialization difficulties, and ASD. There is also a higher incidence than in the general population of strabismus, otitis media, and mitral valve prolapse. In addition, one of the most common medical problems associated with FXS is an increased risk of seizures. A subset of individuals carrying the full mutation of the FMR1 gene and diagnosed with fragile X syndrome (FXS) are reported to experience seizures, mostly during the first 10 years of their life span. Methods As part of a larger project to identify genetic variants that modify the risk of seizures, we collected clinical information from 49 carriers with FXS who experienced seizures and 46 without seizures. We compared seizure type and comorbid conditions based on the source of data as well as family history of seizures. Results We found that the concordance of seizure types observed by parents and medical specialists varied by type of seizure. The most common comorbid condition among those with seizures was autism spectrum disorder (47% per medical records vs. 33% per parent report compared with 19% among those without seizures per parent report); the frequency of other comorbid conditions did not differ among groups. We found a slightly higher frequency of family members who experienced seizures among the seizure group compared with the nonseizure group. Conclusion This study confirms previously reported features of seizures in FXS, supports additional genetic factors, and highlights the importance of information sources, altogether contributing to a better understanding of seizures in FXS.

BackgroundEarly adolescence is a time of psychological and social change that can coincide with declines in mental health and well-being. This study investigated the psychological and social impacts of the COVID-19 pandemic from the perspective of students who responded to a survey in Grades 7 and 8 (ages 12–14) in British Columbia (BC), Canada. The objectives of this study were (i) to provide an overview on early adolescents' experiences and social-emotional well-being during the pandemic; and (ii) to examine whether changes in social experiences as well as feeling safe from getting COVID-19 at school were associated with changes in well-being outcomes over the course of a year.MethodsA sample of n = 1,755 students from a large public school district self-reported on their life satisfaction, optimism, and symptoms of sadness across two time points: First, in their Grade 7 year (pre-pandemic; January to March, 2020) and then 1 year later in their Grade 8 year (during the pandemic; January to March, 2021). In Grade 8, students also reported on pandemic-specific experiences, including changes in mental health, social relationships, and activities, as well as coping strategies and positive changes since the pandemic. Data were collected online using the Middle Years Development Instrument (MDI), a population-based self-report tool that assesses children's social-emotional development and well-being in the context of their home, school, and neighborhood. Multivariable linear regression analyses were used to examine associations between pandemic-related changes in relationships and perceived safety from getting COVID-19 at school with changes in well-being outcomes.ResultsStudents reported a range of experiences, with a large proportion reporting moderate concerns and impacts of the pandemic, including worries about their mental health and missing school activities. Students reported significantly lower optimism, lower life satisfaction, and higher sadness compared to the previous year. Within the sample, improvements in relationships with parents and other adults at home was associated with higher well-being during the pandemic.ImplicationsResults from this study can inform decision making of policy-makers, educators, and practitioners working with youth, by providing information on students' experiences during the pandemic and identifying factors that may be protective for students' mental health during and beyond the pandemic.

Summary: Transcriptional silencing of the FMR1 gene in fragile X syndrome (FXS) leads to the loss of the RNA-binding protein FMRP. In addition to regulating mRNA translation and protein synthesis, emerging evidence suggests that FMRP acts to coordinate proliferation and differentiation during early neural development. However, whether loss of FMRP-mediated translational control is related to impaired cell fate specification in the developing human brain remains unknown. Here, we use human patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells and organoids to model neurogenesis in FXS. We developed a high-throughput, in vitro assay that allows for the simultaneous quantification of protein synthesis and proliferation within defined neural subpopulations. We demonstrate that abnormal protein synthesis in FXS is coupled to altered cellular decisions to favor proliferative over neurogenic cell fates during early development. Furthermore, pharmacologic inhibition of elevated phosphoinositide 3-kinase (PI3K) signaling corrects both excess protein synthesis and cell proliferation in a subset of patient neural cells.

Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods: A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

The solution to the job shop scheduling problem (JSSP) is of great significance for improving resource utilization and production efficiency of enterprises. In this paper, in view of its non-deterministic polynomial properties, a multi-agent genetic algorithm based on tabu search (MAGATS) is proposed to solve JSSPs under makespan constraints. Firstly, a multi-agent genetic algorithm (MAGA) is proposed. During the process, a multi-agent grid environment is constructed based on characteristics of multi-agent systems and genetic algorithm (GA), and a corresponding neighbor interaction operator, a mutation operator based on neighborhood structure and a self-learning operator are designed. Then, combining tabu search algorithm with a MAGA, the algorithm MAGATS are presented. Finally, 43 benchmark instances are tested with the new algorithm. Compared with four other algorithms, the optimization performance of it is analyzed based on obtained test results. Effectiveness of the new algorithm is verified by analysis results.