Multi-scale signaling and tumor evolution in high-grade gliomas.

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.

Automated single-cell proteomics providing sufficient proteome depth to study complex biology beyond cell type classifications.

The recent technological and computational advances in mass spectrometry-based single-cell proteomics have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell remains challenging. To address some of those limitations, we present a dedicated sample preparation chip, the proteoCHIP EVO 96 that directly interfaces with the Evosep One. This, in combination with the Bruker timsTOF demonstrates double the identifications without manual sample handling and the newest generation timsTOF Ultra identifies up to 4000 with an average of 3500 protein groups per single HEK-293T without a carrier or match-between runs. Our workflow spans 4 orders of magnitude, identifies over 50 E3 ubiquitin-protein ligases, and profiles key regulatory proteins upon small molecule stimulation. This study demonstrates that the proteoCHIP EVO 96-based sample preparation with the timsTOF Ultra provides sufficient proteome depth to study complex biology beyond cell-type classifications.

Development and organization of the retinal orientation selectivity map.

Orientation or axial selectivity, the property of neurons in the visual system to respond preferentially to certain angles of visual stimuli, plays a pivotal role in our understanding of visual perception and information processing. This computation is performed as early as the retina, and although much work has established the cellular mechanisms of retinal orientation selectivity, how this computation is organized across the retina is unknown. Using a large dataset collected across the mouse retina, we demonstrate functional organization rules of retinal orientation selectivity. First, we identify three major functional classes of retinal cells that are orientation selective and match previous descriptions. Second, we show that one orientation is predominantly represented in the retina and that this predominant orientation changes as a function of retinal location. Third, we demonstrate that neural activity plays little role on the organization of retinal orientation selectivity. Lastly, we use in silico modeling followed by validation experiments to demonstrate that the overrepresented orientation aligns along concentric axes. These results demonstrate that, similar to direction selectivity, orientation selectivity is organized in a functional map as early as the retina.

"I am in favour of organ donation, but I feel you should opt-in"-qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England.

BACKGROUND: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. METHODS: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. RESULTS: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. CONCLUSIONS: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. TRIAL REGISTRATION: National Institute of Health Research (NIHR) [IRAS 275992].

Development and Organization of the Retinal Orientation Selectivity Map.

Orientation or axial selectivity, the property of neurons in the visual system to respond preferentially to certain angles of a visual stimuli, plays a pivotal role in our understanding of visual perception and information processing. This computation is performed as early as the retina, and although much work has established the cellular mechanisms of retinal orientation selectivity, how this computation is organized across the retina is unknown. Using a large dataset collected across the mouse retina, we demonstrate functional organization rules of retinal orientation selectivity. First, we identify three major functional classes of retinal cells that are orientation selective and match previous descriptions. Second, we show that one orientation is predominantly represented in the retina and that this predominant orientation changes as a function of retinal location. Third, we demonstrate that neural activity plays little role on the organization of retinal orientation selectivity. Lastly, we use in silico modeling followed by validation experiments to demonstrate that the overrepresented orientation aligns along concentric axes. These results demonstrate that, similar to direction selectivity, orientation selectivity is organized in a functional map as early as the retina. One Sentence Summary: Development and organization of retinal orientation selectivity.

Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers.

PURPOSE: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications. EXPERIMENTAL DESIGN: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model. RESULTS: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and lower grades (grade 1/2, 43.2% vs. 8.1%, all P < 0.0001). The highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n = 9/9), mesonephric-like ovarian (83.3%, n = 5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival [hazard ratio (HR) = 1.3; P = 0.001]. Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN (28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS + MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy [8.4 years [(95% confidence interval (CI), 5.5-12.0) vs. 5.5 years (95% CI, 4.6-6.6); HR = 0.67; P = 0.031], this effect did not persist in multivariable analysis. CONCLUSIONS: RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.

Automated single-cell proteomics providing sufficient proteome depth to study complex biology beyond cell type classifications.

Mass spectrometry (MS)-based single-cell proteomics (SCP) has gained massive attention as a viable complement to other single cell approaches. The rapid technological and computational advances in the field have pushed the boundaries of sensitivity and throughput. However, reproducible quantification of thousands of proteins within a single cell at reasonable proteome depth to characterize biological phenomena remains a challenge. To address some of those limitations we present a combination of fully automated single cell sample preparation utilizing a dedicated chip within the picolitre dispensing robot, the cellenONE. The proteoCHIP EVO 96 can be directly interfaced with the Evosep One chromatographic system for in-line desalting and highly reproducible separation with a throughput of 80 samples per day. This, in combination with the Bruker timsTOF MS instruments, demonstrates double the identifications without manual sample handling. Moreover, relative to standard high-performance liquid chromatography, the Evosep One separation provides further 2-fold improvement in protein identifications. The implementation of the newest generation timsTOF Ultra with our proteoCHIP EVO 96-based sample preparation workflow reproducibly identifies up to 4,000 proteins per single HEK-293T without a carrier or match-between runs. Our current SCP depth spans over 4 orders of magnitude and identifies over 50 biologically relevant ubiquitin ligases. We complement our highly reproducible single-cell proteomics workflow to profile hundreds of lipopolysaccharide (LPS)-perturbed THP-1 cells and identified key regulatory proteins involved in interleukin and interferon signaling. This study demonstrates that the proteoCHIP EVO 96-based SCP sample preparation with the timsTOF Ultra provides sufficient proteome depth to study complex biology beyond cell-type classifications.

Exploring the biopsychosocial impact of hypermobility spectrum disorders and Ehlers-Danlos syndrome in an adult population: a protocol for a scoping review.

BACKGROUND: Conditions such as hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndrome (EDS) are most often diagnosed when an individual has joint flexibility beyond the normal physiological limits. Additional characteristics and symptoms include pain and fatigue with individuals also being more likely to report feelings of anxiety and depression. Due to the varied presentation of these conditions, there is a lack of understanding amongst the various healthcare professionals (HCPs) individuals present to, leading to delayed diagnoses and negative experiences for the individuals themselves. This scoping review therefore aims to map the known biopsychosocial impact of adults with HSD and EDS. METHODS: The scoping review will follow the six-step framework as outlined by Arskey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) checklist. The search will be conducted using the following databases: AMED, CINAHL, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed PEDro. Full-text published articles in the English language (excluding literature and systematic reviews) with adult samples (over the age of 18 years) and a diagnosis of a HSD or EDS, published between 2012 and 2022, will be included in the review. DISCUSSION: This review will aim to explore the existing literature for the reported biopsychosocial impact of adults with a HSD or EDS. It will also aim to further acknowledge the gaps in understanding of the condition, how the condition and the impact of the condition is being measured and what HCPs are involved in supporting such individuals. These gaps will be used to inform a future systematic review. It is the overall goal to increase the knowledge of HCPs and the quality of life of adults living with a joint hypermobility condition.

Psychological interventions to improve pain, fatigue, anxiety, depression, and quality of life in children and adults with hypermobility spectrum disorders and Ehlers-Danlos syndrome: a systematic review.

Hypermobility spectrum disorders (HSD) affect individuals across physical, psychological and social domains, making assessment and management difficult. Management for this condition primarily focuses on addressing the musculoskeletal complaints using physiotherapy rather than the additional manifestations such as fatigue, anxiety and depression. This systematic review aims to identify psychological interventions and assess whether they improve the lived experiences of individuals with HSD. It also aims to assess which psychological interventions were most effective, which symptoms were most effectively managed by a psychological intervention, and whether there were differences between children and adults. Studies were included if they were a randomised controlled trial or pre/post-test design, a sample of any age and clinical diagnosis of HSD (including Ehlers-Danlos syndrome), used a psychological intervention and assessed the effect of the intervention on lived experiences using appropriate outcome measures. Risk of bias was assessed using the Mixed Methods Appraisal Tool. The results were narratively synthesised. Six studies were included in the review, one isolated psychological intervention and five incorporated a psychological intervention within a multidisciplinary programme. The interventions predominantly aimed to reduce pain including intensity, interference, pain-related fear and catastrophising, with anxiety and depression, affect, daily living, fatigue also being evaluated. The most beneficial psychological interventions were those delivered alongside physiotherapy in an outpatient or community setting, improving both the physical and psychological aspects of pain, subsequently improving quality of life. However, there lacks randomised controlled trials with larger samples to definitively confirm the significant findings discussed in this review.

Phosphorylation Dynamics in a flg22-Induced, G Protein-Dependent Network Reveals the AtRGS1 Phosphatase.

The microbe-associated molecular pattern flg22 is recognized in a flagellin-sensitive 2-dependent manner in root tip cells. Here, we show a rapid and massive change in protein abundance and phosphorylation state of the Arabidopsis root cell proteome in WT and a mutant deficient in heterotrimeric G-protein-coupled signaling. flg22-induced changes fall on proteins comprising a subset of this proteome, the heterotrimeric G protein interactome, and on highly-populated hubs of the immunity network. Approximately 95% of the phosphorylation changes in the heterotrimeric G-protein interactome depend, at least partially, on a functional G protein complex. One member of this interactome is ATBα, a substrate-recognition subunit of a protein phosphatase 2A complex and an interactor to Arabidopsis thaliana Regulator of G Signaling 1 protein (AtRGS1), a flg22-phosphorylated, 7-transmembrane spanning modulator of the nucleotide-binding state of the core G-protein complex. A null mutation of ATBα strongly increases basal endocytosis of AtRGS1. AtRGS1 steady-state protein level is lower in the atbα mutant in a proteasome-dependent manner. We propose that phosphorylation-dependent endocytosis of AtRGS1 is part of the mechanism to degrade AtRGS1, thus sustaining activation of the heterotrimeric G protein complex required for the regulation of system dynamics in innate immunity. The PP2A(ATBα) complex is a critical regulator of this signaling pathway.

Belonging Exacerbates the Relations Between Racial Climate Stress and Physiological Dysregulation.

OBJECTIVE: Belonging is often considered a buffer against the physical and emotional consequences of discrimination and racial climate stress Youth Soc. 48(5):649-72, 2016. However, recent research suggests that feelings of belonging toward an institution can be detrimental when an individual feels discriminated against by the same institution to which one feels a sense of connection J Behav Med. 44(4):571-8, 2021. Therefore, the present study aimed to investigate the moderating role of institutional belonging in the relationship between racial climate stress and health, as indexed by allostatic load (AL), a multi-system indicator of physiological dysregulation. METHODS: In a sample of Black and White college students (N = 150; White = 82; Black = 68), self-reported racial climate stress, institutional belonging, and various demographic variables were collected. An AL composite was also collected, comprised of six biological measures of the SAM system, HPA axis, cardiovascular system, and metabolic system. Multiple regression analyses were conducted to explore the relationships between these variables. RESULTS: Results demonstrated no main effect of racial climate stress on AL but did show a significant interaction between racial climate stress and belonging, such that the positive relationship between racial climate stress and AL was significant only for those who also felt high levels of institutional belonging (ß int = .05, p = .006, 95% CI = 0.01 - 0.08). CONCLUSIONS: Feeling a sense of belonging may have negative physiological consequences for those who experience racial climate stress in a college setting.

A Practical Guide to Inferring Multi-Omics Networks in Plant Systems.

The inference of gene regulatory networks can reveal molecular connections underlying biological processes and improve our understanding of complex biological phenomena in plants. Many previous network studies have inferred networks using only one type of omics data, such as transcriptomics. However, given more recent work applying multi-omics integration in plant biology, such as combining (phospho)proteomics with transcriptomics, it may be advantageous to integrate multiple omics data types into a comprehensive network prediction. Here, we describe a state-of-the-art approach for integrating multi-omics data with gene regulatory network inference to describe signaling pathways and uncover novel regulators. We detail how to download and process transcriptomics and (phospho)proteomics data for network inference, using an example dataset from the plant hormone signaling field. We provide a step-by-step protocol for inference, visualization, and analysis of an integrative multi-omics network using currently available methods. This chapter serves as an accessible guide for novice and intermediate bioinformaticians to analyze their own datasets and reanalyze published work.

Attitudes to Organ Donor Registration in England Under Opt-Out Legislation.

Introduction: In England, everyone is considered an organ donor unless they have registered for opt-out donation. Research Question: This study evaluated positive statements and negative affective attitudes against anticipated organ donor status and whether the order in the attitudes and statements presented impacted organ donor intention under an opt-out system. Design: A quasi-experimental mixed between-within design was employed with participants assigned to 1 of 2 conditions. Participants in the first condition received negative affective attitude statements followed by positive statements. This was reversed in the second condition to combat ordering effects. Participants (N = 679) were asked about their donor status under an opt-out system. There were three groups: opt-in (actively), opt-out/not sure, and deemed consent (no objection). Organ donor intentions were measured at three intervals: baseline, post-positive statements, and post-negative attitudes. Results: Approximately 10% of participants would opt-out or were unsure of their intentions to be an organ donor under an opt-out system. Significant effects were found in both positive statements and negative affective attitudes. All groups expressed greater medical mistrust and were most influenced by cognitive attitudes. Conclusions: Under the opt-out system in England, it is anticipated that the majority would actively opt-in or have no objection to being automatically registered as an organ donor. Public health campaigns would benefit from promoting the most influential positive statements and refuting the most detrimental negative attitudes to increase intentions of those who plan to opt-out or are unsure.

The class VIII myosin ATM1 is required for root apical meristem function.

Myosins are evolutionarily conserved motor proteins that interact with actin filaments to regulate organelle transport, cytoplasmic streaming and cell growth. Plant-specific class XI myosin proteins direct cell division and root organogenesis. However, the roles of plant-specific class VIII myosin proteins in plant growth and development are less understood. Here, we investigated the function of an auxin-regulated class VIII myosin, Arabidopsis thaliana MYOSIN 1 (ATM1), using genetics, transcriptomics and live cell microscopy. ATM1 is associated with the plasma membrane and plasmodesmata within the root apical meristem (RAM). Loss of ATM1 function results in decreased RAM size and reduced cell proliferation in a sugar-dependent manner. Auxin signaling and transcriptional responses were dampened in atm1-1 roots. Complementation of atm1-1 with a tagged ATM1 driven under the native ATM1 promoter restored root growth and cell cycle progression. Genetic analyses of atm1-1 seedlings with HEXOKINASE 1 (HXK1) and TARGET OF RAPAMYCIN COMPLEX 1 (TORC1) overexpression lines indicate that ATM1 is downstream of TOR. Collectively, these results provide previously unreported evidence that ATM1 functions to influence cell proliferation in primary roots in response to auxin and sugar cues.

Weed-induced changes in the maize root transcriptome reveal transcription factors and physiological processes impacted early in crop-weed interactions.

A new paradigm suggests weeds primarily reduce crop yield by altering crop developmental and physiological processes long before the weeds reduce resources through competition. Multiple studies have implicated stress response pathways are activated when crops such as maize are grown in close proximity with weeds during the first 4-8 weeks of growth-the point at which weeds have their greatest impact on subsequent crop yields. To date, these studies have mostly focused on the response of above-ground plant parts and have not examined the early signal transduction processes associated with maize root response to weeds. To investigate the impact of signals from a below-ground competitor on the maize root transcriptome when most vulnerable to weed pressure, a system was designed to expose maize to only below-ground signals. Gene set enrichment analyses identified over-represented ontologies associated with oxidative stress signalling throughout the time of weed exposure, with additional ontologies associated with nitrogen use and transport and abscisic acid (ABA) signalling, and defence responses being enriched at later time points. Enrichment of promoter motifs indicated over-representation of sequences known to bind FAR-RED IMPAIRED RESPONSE 1 (FAR1), several AP2/ERF transcription factors and others. Likewise, co-expression networks were identified using Weighted-Gene Correlation Network Analysis (WGCNA) and Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) algorithms. WGCNA highlighted the potential roles of several transcription factors including a MYB 3r-4, TB1, WRKY65, CONSTANS-like5, ABF3, HOMEOBOX 12, among others. These studies also highlighted the role of several specific proteins involved in ABA signalling as being important for the initiation of the early response of maize to weeds. SC-ION highlighted potential roles for NAC28, LOB37, NAC58 and GATA2 transcription factors, among many others.

NHS staff awareness, attitudes and actions towards the change in organ donation law in England-results of the #options survey 2020.

BACKGROUND: In Spring 2020 there was a change in organ donation legislation in England (UK). Much is known about public opinions to organ donation and the change in legislation, however, there is little evidence about the opinions of the NHS workforce. This study set out to understand the levels of awareness, support and action of NHS staff to this change and explore the impact of respondent demographics, place and type of work on awareness, support and action. METHODS: An online survey was offered to all NHS organisations in North Thames and the North East and North Cumbria through the NIHR Clinical Research Network between July and December 2020. Participating organisations were provided with an information package and promoted the survey via email and internal staff communications. Associations were compared univariately using chi-square tests and logistic regression was used for multivariable analysis to compare findings with NHS Blood and Transplant public Kantar survey data. RESULTS: A total of 5789 staff participated in the survey. They were more aware, more supportive, more likely to have discussed their organ donation choices with family and more likely to be on the organ donor register than the public. This increased awareness and support was found across minority ethnic and religious groups. Those working in a transplanting centre were most aware and supportive and those working in the ambulance service were most likely to 'opt-in' following the change in legislation. CONCLUSIONS: NHS staff in England were well informed about the change in organ donation legislation and levels of support were high. NHS staff were six times more likely than the public to have a conversation with their family about their organ donation choices. The size and ethnic diversity of the NHS workforce offers an opportunity to enable and support NHS staff to be advocates for organ donation and raise awareness of the change in legislation amongst their communities.

Transcription Factor Dynamics in Cross-Regulation of Plant Hormone Signaling Pathways.

Cross-regulation between hormone signaling pathways is indispensable for plant growth and development. However, the molecular mechanisms by which multiple hormones interact and co-ordinate activity need to be understood. Here, we generated a cross-regulation network explaining how hormone signals are integrated from multiple pathways in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. To do so we comprehensively characterized transcription factor activity during plant hormone responses and reconstructed dynamic transcriptional regulatory models for six hormones; abscisic acid, brassinosteroid, ethylene, jasmonic acid, salicylic acid and strigolactone/karrikin. These models incorporated target data for hundreds of transcription factors and thousands of protein-protein interactions. Each hormone recruited different combinations of transcription factors, a subset of which were shared between hormones. Hub target genes existed within hormone transcriptional networks, exhibiting transcription factor activity themselves. In addition, a group of MITOGEN-ACTIVATED PROTEIN KINASES (MPKs) were identified as potential key points of cross-regulation between multiple hormones. Accordingly, the loss of function of one of these (MPK6) disrupted the global proteome, phosphoproteome and transcriptome during hormone responses. Lastly, we determined that all hormones drive substantial alternative splicing that has distinct effects on the transcriptome compared with differential gene expression, acting in early hormone responses. These results provide a comprehensive understanding of the common features of plant transcriptional regulatory pathways and how cross-regulation between hormones acts upon gene expression.

The biopsychosocial impact of hypermobility spectrum disorders in adults: a scoping review.

Joint hypermobility affects approximately 30% of the United Kingdom (UK) population, characterised by the ability to move joints beyond the physiological limits. Associated conditions include Ehlers-Danlos syndrome and hypermobility spectrum disorders, affecting individuals across physical, psychological and social levels detrimentally impacting their health and wellbeing. The scoping review aims to describe the known biopsychosocial impact of joint hypermobility conditions in adults over the last decade. Additional objectives include to (1) identify the types of studies that address these factors, (2) to understand how the impact of the condition is measured and managed and (3) what healthcare professionals (HCPs) are involved. The scoping review was conducted using the five-stage framework by Arksey and O'Malley. The search strategy related to two main keywords, "hypermobility" and, "biopsychosocial" across a number of electronic databases. A pilot search was conducted to determine the suitability of the databases and terms. Following the search, the data was extracted and charted, summarised and narratively reported. 32 studies met the inclusion criteria. The majority were conducted in either the UK or United States of America and case-control in design. The biopsychosocial impact was wide-ranging including, but not limited to, musculoskeletal system and dermatology, gastroenterology, mood and anxiety disorders, education and employments. This review is the first of its kind to summarise all reported symptoms and impact of joint hypermobility conditions in adults, highlighting a clear need to promote a multidisciplinary and holistic approach in raising awareness of these conditions and improving their management.

Understanding Best Practices in Implementation of Behavioral Emergency Response Teams Through a Scoping Review.

BACKGROUND: Health care providers are at risk of suffering physical or emotional abuse from patients, family members, and visitors. This results in decreased job satisfaction, high turnover, increased rates of patient physical and pharmacologic restraint, and poor patient outcomes. Behavioral emergency response teams (BERTs) have proven effective in reducing workplace assaults directed at staff, reducing the rate at which behaviorally disruptive patients are physically or pharmacologically restrained and are associated with increased staff satisfaction. AIMS: This scoping review seeks to highlight the best practices and limitations of BERT use with adult populations in hospital settings to guide future implementation across academic medical centers. METHOD: A literature review was conducted using PubMed, Tisch Library, and Tufts University School of Medicine's search tool "Jumbo Search" to screen articles for a duration from 2000 to 2021. The review was conducted following PRISMA-ScR guidelines using three screens for the inclusion of papers most relevant to the review's aims. RESULTS: BERTs are commonly implemented with trained medical staff. The most common interventions used by the BERTs are de-escalation techniques and education for staff about the incidents. Most BERT implementation involves a proactive screening protocol for identifying high-risk patients and a team-based approach. CONCLUSIONS: BERTS are effective at reducing assaults directed at staff and are associated with increased staff satisfaction. Using a proactive process to identify high-risk patients for disruptive behavior in conjunction with a team-based response to behavioral emergencies, academic medical centers can decrease the use of physical restraints and increase staff satisfaction leading to a higher quality of care.

FERONIA functions through Target of Rapamycin (TOR) to negatively regulate autophagy.

FERONIA (FER) receptor kinase plays versatile roles in plant growth and development, biotic and abiotic stress responses, and reproduction. Autophagy is a conserved cellular recycling process that is critical for balancing plant growth and stress responses. Target of Rapamycin (TOR) has been shown to be a master regulator of autophagy. Our previous multi-omics analysis with loss-of-function fer-4 mutant implicated that FER functions in the autophagy pathway. We further demonstrated here that the fer-4 mutant displayed constitutive autophagy, and FER is required for TOR kinase activity measured by S6K1 phosphorylation and by root growth inhibition assay to TOR kinase inhibitor AZD8055. Taken together, our study provides a previously unknown mechanism by which FER functions through TOR to negatively regulate autophagy.