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The present study investigates how counsellors working with children and young people (CYP) perceive their professional identity, and how the 'Practitioner Manual' and BACP Competence Frameworks, commissioned by the British Association for Counselling & Psychotherapy (BACP; 2014/2019a), can contribute to the strengthening of CYP counsellor professional identity. Participants were qualified counsellors working with CYP clients in England and Scotland. Interpretative Phenomenological Analysis (IPA) was used to analyse data. Findings were organised under three master themes: individual perception of professional identity; others' perceptions of professional identity; role of resources on formation and development of professional identity. Sub-themes included: discomfort with the concept of professionalism; misunderstandings and misconceptions; a desire for a recognised professional identity. Findings indicate that the provision of counselling for CYP clients could be enhanced by establishing a recognised professional identity underpinned by required minimum training standards and leading to registration with a recognised professional body.

Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria (MRE). It has been hypothesized that MRE were acquired by a common ancestor and transmitted vertically. Alternatively, MRE endosymbionts could have invaded after the divergence of Mucoromycota lineages and subsequently spread to new hosts horizontally. To better understand the evolutionary history of MRE symbionts, we generated and analyzed four complete MRE genomes from two Mortierellaceae genera: Linnemannia (MRE-L) and Benniella (MRE-B). These genomes include the smallest known of fungal endosymbionts and showed signals of a tight relationship with hosts including a reduced functional capacity and genes transferred from fungal hosts to MRE. Phylogenetic reconstruction including nine MRE from mycorrhizal fungi revealed that MRE-B genomes are more closely related to MRE from Glomeromycotina than MRE-L from the same host family. We posit that reductions in genome size, GC content, pseudogene content, and repeat content in MRE-L may reflect a longer-term relationship with their fungal hosts. These data indicate Linnemannia and Benniella MRE were likely acquired independently after their fungal hosts diverged from a common ancestor. This work expands upon foundational knowledge on minimal genomes and provides insights into the evolution of bacterial endosymbionts.

The National Water Model (NWM) provides critical analyses and projections of streamflow that support water management decisions. However, the NWM performs poorly in lower-elevation rivers of the western United States (US). The accuracy of the NWM depends on the fidelity of the model inputs and the representation and calibration of model processes and water sources. To evaluate the NWM performance in the western US, we compared observations of river water isotope ratios (18O / 16O and 2H / 1H expressed in δ notation) to NWM-flux-estimated (model) river reach isotope ratios. The modeled estimates were calculated from long-term (2000–2019) mean summer (June, July, and August) NWM hydrologic fluxes and gridded isotope ratios using a mass balance approach. The observational dataset comprised 4503 in-stream water isotope observations in 877 reaches across 5 basins. A simple regression between observed and modeled isotope ratios explained 57.9 % (δ18O) and 67.1 % (δ2H) of variance, although observations were 0.5 ‰ (δ18O) and 4.8 ‰ (δ2H) higher, on average, than mass balance estimates. The unexplained variance suggest that the NWM does not include all relevant water fluxes to rivers. To infer possible missing water fluxes, we evaluated patterns in observation–model differences using δ18Odiff (δ18Oobs−δ18Omod) and ddiff (δ2Hdiff-8⋅δ18Odiff). We detected evidence of evaporation in observations but not model estimates (negative ddiff and positive δ18Odiff) at lower-elevation, higher-stream-order, arid sites. The catchment actual-evaporation-to-precipitation ratio, the fraction of streamflow estimated to be derived from agricultural irrigation, and whether a site was reservoir-affected were all significant predictors of ddiff in a linear mixed-effects model, with up to 15.2 % of variance explained by fixed effects. This finding is supported by seasonal patterns, groundwater levels, and isotope ratios, and it suggests the importance of including irrigation return flows to rivers, especially in lower-elevation, higher-stream-order, arid rivers of the western US.

This paper reviews and assesses the prospects for developing geographically enabled research ready data (RRD) with reference to current UK initiatives. Examples of projects for which such data have been provisioned are given.

Abstract In the United States, maternal health inequities disproportionately affect Global Majority (e.g., Asian, Black, and Hispanic) populations. Despite a substantial body of research underscoring the influence of racism on these inequities, little research has examined how experiences of gendered racial microaggressions during pregnancy and birth impact racially and ethnically diverse Global Majority pregnant and birthing people in obstetric hospital settings. We evaluated the psychometric properties of an adapted version of Lewis & Neville’s Gendered Racial Microaggressions Scale, using data collected from 417 Global Majority birthing people. Findings from our study indicate that our adapted GRMS is a valid tool for assessing the experiences of gendered racial microaggressions in hospital-based obstetric care settings among Global Majority pregnant and birthing people whose preferred languages are English or Spanish. Item Response Theory (IRT) analysis demonstrated high construct validity of the adapted GRMS scale (Root Mean Square Error of Approximation = 0.1089 (95% CI 0.0921, 0.1263), Comparative Fit Index = 0.977, Standardized Root Mean Square Residual = 0.075, log-likelihood c2 = -85.6, df = 8). IRT analyses demonstrated that the unidimensional model was preferred to the bi-dimensional model as it was more interpretable, had lower AIC and BIC, and all items had large discrimination parameters onto a single factor (all discrimination parameters > 3.0). Given that we found similar response profiles among Black and Hispanic respondents, our Differential Item Functioning analyses support validity among Black, Hispanic, and Spanish-speaking birthing people. Inter-item correlations demonstrated adequate scale reliability, α = 0.97, and empirical reliability = 0.67. Pearsons correlations was used to assess the criterion validity of our adapted scale. Our scale’s total score was significantly and positively related to postpartum depression and anxiety. Researchers and practitioners should seek to address instances of gendered racial microaggressions in obstetric settings, as they are manifestations of systemic and interpersonal racism, and impact postpartum health.

ABSTRACT Mucoromycota fungi and their Mollicutes-related endobacteria (MRE) are an ideal system for studying bacterial–fungal interactions and evolution due to the long-term and intimate nature of their interactions. However, methods for detecting MRE face specific challenges due to the poor representation of MRE in sequencing databases coupled with the high sequence divergence of their genomes, making traditional similarity searches unreliable. This has precluded estimations on the diversity of MRE associated with Mucoromycota. To determine the prevalence of previously undetected MRE in fungal genome sequences, we scanned 389 Mucoromycota genome assemblies available from the National Center for Biotechnology Information for the presence of MRE sequences using publicly available tools to map contigs from fungal assemblies to publicly available MRE genomes. We demonstrate a higher diversity of MRE genomes than previously described in Mucoromycota and a lack of cophylogeny between MRE and the majority of their fungal hosts. This supports the late invasion hypothesis regarding MRE acquisition across most of the examined fungal families. In contrast with other Mucoromycota lineages, MRE from the Gigasporaceae displayed some degree of cophylogeny with their hosts, which may indicate that horizontal transmission is restricted between members of this family or that transmission is strictly vertical. These results underscore the need for a refined process to capture sequencing data from potential fungal endosymbionts to discern their evolution and transmission. Screens of fungal genomes for MRE can help improve the quality of fungal genome assemblies while identifying new MRE lineages to further test hypotheses on their origin and evolution.IMPORTANCEMollicutes-related endobacteria (MRE) are obligate intracellular bacteria found within Mucoromycota fungi. Despite their frequent detection, MRE roles in host functioning are still unknown. Comparative genomic investigations can improve our understanding of the impact of MRE on their fungal hosts by identifying similarities and differences in MRE genome evolution. However, MRE genomes have only been assembled from a small fraction of Mucoromycota hosts. Here, we demonstrate that MRE can be present yet undetected in publicly available Mucoromycota genome assemblies. We use these newfound sequences to assess the broader diversity of MRE and their phylogenetic relationships with respect to their hosts. We demonstrate that publicly available tools can be used to extract novel MRE sequences from assembled fungal genomes leading to insights on MRE evolution. This work contributes to a greater understanding of the fungal microbiome, which is crucial to improving knowledge on the dynamics and impacts of fungi in microbial ecosystems.

ABSTRACTWe describe the creation of a data resource for charting the adoption of fixed line telephony in Great Britain over the period 1880–1984, of which the period 1880–1951 is available for wide research use. We first evaluate the use of various open-source software and then develop the novel teldiR open-source package to capture digitally encoded scans of all available telephone directories at ten-yearly intervals throughout this period and document the quality control checks used to establish the provenance of the resulting digital records. Our research demonstrates the feasibility of digitally encoding scans of historical telephone directories, and suggests potential analytical extensions to this work, including georeferencing of subscriber records. This research is seen not only as facilitating geographical analysis of the adoption of fixed line telephony, but also as creating a bridge between historical analysis of residential mobility, migration, and changing geodemographic structure in the years between (now digitized) historical censuses and present day digital sources. The digital resource arising from this research is available for bona fide research use.

Abstract Background Immunocompromised travellers (ICTs) face greater infectious and non-infectious travel-associated risks than their immunocompetent counterparts. Increasing travel and emergence of novel immunosuppressants poses great challenges for travel medicine practitioners to confidently provide up-to-date evidence-based risk management advice and pre-travel care for ICTs. Methods We reviewed the records of ICTs attending the London Hospital for Tropical Diseases (HTD) Travel Clinic between 1st April 2019 and 30th April 2020 with the aim to describe demographic and travel characteristics, type, and severity of immunocompromise, the degree of risk associated with intended travel and evaluate travel advice. Results Of the 193 ICTs identified, immunocompromise was due to physiological reasons (42%), chronic infection (17.1%) and immunosuppressive therapy (16.6%). Median age was 38 (range 9 months to 84 years) and male to female ratio 0.75 (83:110). Travel was intended to 80 countries for a median of 16 days (range 2 to 3167), predominantly for leisure (53%), non-medical work (17%) and visiting friends and relatives (12%). Live vaccine safety dominated discussion in the pre-travel consultation. Existing guidelines arguably fell short in dealing with travel risks associated with hyper-specific conditions, targeted immunosuppressants and non-vaccine preventable infections. Conclusions Our cohort represents a wide spectrum of immunocompromise, for whom we arguably need more measurable ways to approach travel-associated risks. We propose prospective qualitative participatory research to inform our unit of the priorities of ICTs in the pre-travel consultation. We further recommend the formation of a repository of specialists and formulary of complex cases to direct subsequent informative systematic review and prospective risk studies.

Objective Inducing tumour cell apoptosis is a primary objective of chemotherapy but, to date, there are no validated biomarkers of apoptosis sensitivity or resistance. Our objective was to image multiple apoptosis pathway proteins at single cell level and determine multi-protein associations with recurrence risk and chemotherapy response in patients with stage II colorectal cancer (CRC).Methods and analysis Multiplexed imaging of 16 proteins in the intrinsic and extrinsic apoptosis pathways at single cell resolution on resected tissue from 194 patients with stage II CRC who either received adjuvant chemotherapy (n=108) or were treated with surgery only (n=86). K-means clustering of >600 000 cancer cells and cell level intensities of APAF1, procaspase-9, procaspase-3, XIAP, SMAC, BAX, BAK, BCL2, BCL-XL, MCL-1, procaspase-8, BID, FADD, FLIP, RIP3 and CIAP1 identified distinct cell cluster profiles.Results Chemotherapy-treated patients with a higher percentage of cell clusters with low procaspase-3 and high XIAP had a higher risk of recurrence. This was validated in an independent cohort of adjuvant chemotherapy-treated high-risk patients with stage II CRC. We also applied two established system models of apoptosis initiation and execution to estimate cellular apoptosis sensitivity and show that these cell clusters do not appear to have impaired mitochondrial outer membrane permeabilisation sensitivity, but downstream procaspase-3 cleavage is compromised. This represents a key characteristic of drug-tolerant ‘persister’ cells.Conclusion This study represents the most comprehensive analysis to date of apoptosis protein distribution at single cell level in CRC tumours. Our study identifies a subgroup of patients with stage II CRC with an apoptosis-resistant ‘persister’ cell profile who do not benefit from adjuvant chemotherapy.

Diverse and complex microbiomes are found in virtually every environment on Earth. Bacteria and fungi often co-dominate environmental microbiomes, and there is growing recognition that bacterial-fungal interactions (BFI) have significant impacts on the functioning of their associated microbiomes, environments, and hosts. Investigating BFI in vitro remains a challenge, particularly when attempting to examine interactions at multiple scales of system complexity. Fabricated devices can provide control over both biotic composition and abiotic factors within an experiment to enable the characterization of diverse BFI phenotypes such as modulation of growth rate, production of biomolecules, and alterations to physical movements. Engineered devices ranging from microfluidic chips to simulated rhizosphere systems have been and will continue to be invaluable to BFI research, and it is anticipated that such devices will continue to be developed for diverse applications in the field. This will allow researchers to address specific questions regarding the nature of BFI and how they impact larger microbiome and environmental processes such as biogeochemical cycles, plant productivity, and overall ecosystem resilience. Devices that are currently used for experimental investigations of bacteria, fungi, and BFI are discussed herein along with some of the associated challenges and several recommendations for future device design and applications.

IntroductionIn areas where malaria transmission has been successfully reduced, surveillance based solely on clinical cases becomes increasingly challenging. Antibodies generated by the host in response to malaria infections may persist in the circulation for several months or longer. We assessed a serological surveillance tool to measure malaria transmission in eastern Indonesia where reported cases have been recently declining.MethodsIn June 2021, we conducted a cross-sectional survey of elementary schoolchildren aged 5 to 14 years residing in six villages in an endemic area of West Timor, Indonesia. Annual Parasite Incidence (API, cases/1,000 residents/year) of these villages ranged from 0.0 to 4.1 in 2021. Finger-prick plasma samples were tested using a multiplexed Luminex MAGPIX® bead array system to measure IgG antibodies against a panel of 8 Plasmodium vivax antigens. Using a random forest classification algorithm, individuals with predicted exposure to P. vivax in the prior 9 months were identified.Results15 of 398 (4%) schoolchildren were seropositive for recent P. vivax exposure. Remarkably, 87% (13/15) of seropositive children were from one village, the one with the highest API (4.1). In contrast, one seropositive child was from a village with an API of 1.3, and another from a village with an API of 0.0.ConclusionOur serological survey data confirms the reported malaria cases from PHC in the villages with likely ongoing transmission. Malaria programs may consider Lamea as the target for intervention.

Vygotsky (1978) describes play as having three main components, one being the ability for a child to create an imaginary situation, the second taking on and acting out roles, and the third, following a set of rules that were determined by the roles children took on during play during social or group settings. Hence, supporting much needed social skills and processes that foster a positive social development. The ambiguities of play, specifically the intricate functions between what play entails and the aligned developmental outcomes of play, makes defining play challenging. Research has revealed that children who are in isolated environments, with reduced physical contact among peers of their own age, tend to have lower levels of academic achievements, and are more susceptible to long term psychological stress as they get older (Ammermueller, 2012; Lacey, Kumari & Bartley, 2014). Specifically, the trauma of isolation affects both the social and cognitive domains of development among preschoolers. Isolation, also takes a toll on the type of play children can engage in. The lack of play during a pandemic can prevent children from feeling a sense of joy and familiarity. This article describes how play is not just a mechanism for supporting academic achievement in young children, but also a form of supporting emotional survival during a crisis.

Abstract Background Over the last decades, the number of malaria cases has drastically reduced in Cambodia. As the overall prevalence of malaria in Cambodia declines, residual malaria transmission becomes increasingly fragmented over smaller remote regions. The aim of this study was to get an insight into the burden and epidemiological parameters of Plasmodium infections on the forest-fringe of Cambodia. Methods 950 participants were recruited in the province of Mondulkiri in Cambodia and followed up from 2018 to 2020. Whole-blood samples were processed for Plasmodium spp. identification by PCR as well as for a serological immunoassay. A risk factor analysis was conducted for Plasmodium vivax PCR-detected infections throughout the study, and for P. vivax seropositivity at baseline. To evaluate the predictive effect of seropositivity at baseline on subsequent PCR-positivity, an analysis of P. vivax infection-free survival time stratified by serological status at baseline was performed. Results Living inside the forest significantly increased the odds of P. vivax PCR-positivity by a factor of 18.3 (95% C.I. 7.7–43.5). Being a male adult was also a significant predictor of PCR-positivity. Similar risk profiles were identified for P. vivax seropositivity. The survival analysis showed that serological status at baseline significantly correlated with subsequent infection. Serology is most informative outside of the forest, where 94.0% (95% C.I. 90.7–97.4%) of seronegative individuals survived infection-free, compared to 32.4% (95% C.I.: 22.6–46.6%) of seropositive individuals. Conclusion This study justifies the need for serological diagnostic assays to target interventions in this region, particularly in demographic groups where a lot of risk heterogeneity persists, such as outside of the forest.

Abstract The activation of apoptosis signalling by TRAIL (TNF-related apoptosis-inducing ligand) through receptor binding is a fundamental mechanism of cell death induction and is often perturbed in cancer cells to enhance their cell survival and treatment resistance. Ubiquitination plays an important role in the regulation of TRAIL-mediated apoptosis, and here we investigate the role of the E3 ubiquitin ligase Itch in TRAIL-mediated apoptosis in oesophageal cancer cells. Knockdown of Itch expression results in resistance to TRAIL-induced apoptosis, caspase-8 activation, Bid cleavage and also promotes cisplatin resistance. Whilst the assembly of the death-inducing signalling complex (DISC) at the plasma membrane is not perturbed relative to the control, TRAIL-R2 is mis-localised in the Itch-knockdown cells. Further, we observe significant changes to mitochondrial morphology alongside an increased cholesterol content. Mitochondrial cholesterol is recognised as an important anti-apoptotic agent in cancer. Cells treated with a drug that increases mitochondrial cholesterol levels, U18666A, shows a protection from TRAIL-induced apoptosis, reduced caspase-8 activation, Bid cleavage and cisplatin resistance. We demonstrate that Itch knockdown cells are less sensitive to a Bcl-2 inhibitor, show impaired activation of Bax, cytochrome c release and an enhanced stability of the cholesterol transfer protein STARD1. We identify a novel protein complex composed of Itch, the mitochondrial protein VDAC2 and STARD1. We propose a mechanism where Itch regulates the stability of STARD1. An increase in STARD1 expression enhances cholesterol import to mitochondria, which inhibits Bax activation and cytochrome c release. Many cancer types display high mitochondrial cholesterol levels, and oesophageal adenocarcinoma tumours show a correlation between chemotherapy resistance and STARD1 expression which is supported by our findings. This establishes an important role for Itch in regulation of extrinsic and intrinsic apoptosis, mitochondrial cholesterol levels and provides insight to mechanisms that contribute to TRAIL, Bcl-2 inhibitor and cisplatin resistance in cancer cells.

Abstract Kaplan–Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher’s toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses. surviveR is a cloud-based Shiny application, that addresses our identified unmet need for an easy-to-use web-based tool that can plot and analyse survival based datasets. Integrated customization options allows a user with limited computational expertise to easily filter patients to enable custom cohort generation, automatically calculate log-rank test and Cox hazard ratios. Continuous datasets can be integrated, such as RNA or protein expression measurements which can be then used as categories for survival plotting. We further demonstrate the utility through exemplifying its application to a clinically relevant colorectal cancer patient dataset. surviveR is a cloud-based web application available at https://generatr.qub.ac.uk/app/surviveR , that can be used by non-experts users to perform complex custom survival analysis.

PurposeAging and mental illness both represent significant public health challenges for incarcerated people in the USA. The COVID-19 pandemic has further highlighted the vulnerabilities of incarcerated people because of the risks of infectious disease transmission in correctional facilities. Focusing on older adults with mental illness, this paper aims to examine efforts to decarcerate US correctional facilities during the COVID-19 pandemic and whether these approaches may lead to sustainable reforms beyond the pandemic.Design/methodology/approachA narrative literature review was conducted using numerous online resources, including PubMed, Google Scholar and LexisNexis. Search terms used included "decarceration pandemic," "COVID-19 decarceration," "aging mental illness decarceration," "jails prisons decarceration," "early release COVID-19" and "correctional decarceration pandemic," among others. Given the rapidly changing nature of the COVID-19 pandemic, this narrative literature review included content from not only scholarly articles and federal and state government publications but also relevant media articles and policy-related reports. The authors reviewed these sources collaboratively to synthesize a review of existing evidence and opinions on these topics and generate conclusions and policy recommendations moving forward.FindingsTo mitigate the risks of COVID-19, policymakers have pursued various decarceration strategies across the USA. Some efforts have focused on reducing inflow into correctional systems, including advising police to reduce numbers of arrests and limiting use of pretrial detention. Other policies have sought to increase outflow from correctional systems, such as facilitating early release of people convicted of nonviolent offenses or those nearing the end of their sentences. Given the well-known risks of COVID-19 among older individuals, age was commonly cited as a reason for diverting or expediting release of people from incarceration. In contrast, despite their vulnerability to complications from COVID-19, people with serious mental illness (SMI), particularly those with acute treatment needs, may have been less likely in some instances to be diverted or released early from incarceration.Originality/valueAlthough much has been written about decarceration during the COVID-19 pandemic, little attention has been paid to the relevance of these efforts for older adults with mental illness. This paper synthesizes existing proposals and evidence while drawing attention to the public health implications of aging and SMI in US correctional settings and explores opportunities for decarceration of older adults with SMI beyond the COVID-19 pandemic.

Previous research has highlighted the need to improve teacher education programs with the intent of preparing infant-toddler professionals as working with infants-toddlers and families requires a unique skill set. The following mixed methods research study supported these assertions by examining the early childhood education (ECE) undergraduate teacher preparation course content in a large northeastern state, through document analysis and a survey of faculty. The findings indicated that very few of the research-based, best practices (relationship-based practices, family-centered practices, creating environments, reflective and ethical practices, and fieldwork experience in high-quality classrooms with children under three), identified for working with infants and toddlers were the main-focus of any of the ECE undergraduate teacher preparation courses. This research offers recommendations for ways that undergraduate ECE teacher preparation programs can support the infant-toddler workforce. The recommendations include adding dedicated infant-toddler courses and supervised fieldwork opportunities with children from birth to 36 months into ECE undergraduate coursework.

Community colleges have a significant role in preparing early childhood educators who will likely one day teach in inclusive classrooms. Inclusive education models educate children with disabilities alongside their non-disabled peers, promoting acceptance, decreasing discrimination, and fostering a society in which everyone lives and works together. Teachers' experiences in working with children who have disabilities and attitudes toward disability affect teacher behavior and practice. The preservice teacher training years are important for preparing teacher candidates to teach in inclusive classrooms; thus, it is imperative that teacher educators have knowledge of methods that will positively impact teacher attitudes toward disability and offer experiences in classrooms with children who have disabilities. This study investigated the effect of an introductory special education course at a community college that included a fieldwork component in inclusive classrooms, as well as the ability status of the course's professor on early childhood preservice teachers' attitudes toward disability. Mixed methods pre- and posttest data was collected from 108 students enrolled in a large urban community college's teacher education program. Students attended class in-person with a professor who had a disability, in-person with a professor who did not have a disability, or online. Posttest results indicated that student attitudes toward disability became significantly more favorable after completing the course, but the professor's disability status did not influence the change. While there were positive changes, some students continued to objectify disability and perceive disability with a deficit lens. Further research is needed to foster positive attitudes toward disability in teachers.

Understanding writing as a performative material practice, this paper highlights the "imperative" as a strategy to enhance writing practices in our classrooms and academic workshops. Drawing on posthuman theories and intra-active relationships, it describes how performative arts-based writing can provide a way to engage with the human and nonhuman, the embodied, sensory elements of our writerly worlds. Employing a critical collaborative autoethnographic methodology, the two authors provide a narrative account of a year as two research Fellows in a university exploring writing as a method of inquiry through designing and implementing a series of performative arts-based writing activities.

Early childhood educators take on many roles over the course of their careers. One role is that of mentor. Although mentors serve a variety of functions, they primarily act as role models, facilitators, and collaborators (Kupila, Ukkonen-Mikkola, & Rantala, 2017). Mentors offer advice, guidance, counseling (Altes & Pinholster, 2013), support, and assistance. This arrangement can be formal, such as when it is organized through an organization, or informal, such as when a person asks someone with more experience to be their mentor. In early childhood education, mentoring can involve teachers working with volunteers, student interns, teacher's aides, assistant teachers, newer teachers, and/or experienced teachers. It is different from supervising, as mentors do not evaluate the person being mentored, the mentee (Walkington, 2005). There is a reciprocal process between the mentor and the mentee, as both grow during the mentoring process (Graves, 2010; Hobbs & Stovall, 2015; Kupila et al., 2017). This growth of mentor and mentee occurs in the context of their relationship, so the quality of the relationship is vital to the success of mentoring. This article outlines three components of an effective mentoring relationship in early childhood settings: (1) relationship-based practices; (2) communication; and (3) reflective practices. This is not a complete list of the ingredients for effective relationships; however, these are the essential, foundational elements needed to build and develop effective mentoring relationships in early childhood settings.

Abstract Background Understanding how to modulate the microenvironment of tumors that are resistant to immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate the ability of USP7 inhibitors to reprogram the tumor microenvironment (TME) by inhibiting secretion of vascular endothelial growth factor (VEGF) from fibroblasts. Methods To understand the role played by USP7 in the TME, we systematically evaluated the effects of potent, selective USP7 inhibitors on co‐cultures comprising components of the TME, using human primary cells. We also evaluated the effects of USP7 inhibition on tumor growth inhibition in syngeneic models when dosed in combination with immune checkpoint inhibitors (ICIs). Results Abrogation of VEGF secretion from fibroblasts in response to USP7 inhibition resulted in inhibition of tumor neoangiogenesis and increased tumor recruitment of CD8‐positive T‐lymphocytes, leading to significantly improved sensitivity to immune checkpoint inhibitors. In syngeneic models, treatment with USP7 inhibitors led to striking tumor responses resulting in significantly improved survival. Conclusions USP7‐mediated reprograming of the TME is not linked to its previously characterized role in modulating MDM2 but does require p53 and UHRF1 in addition to the well‐characterized VEGF transcription factor, HIF‐1α. This represents a function of USP7 that is unique to fibroblasts, and which is not observed in cancer cells or other components of the TME. Given the potential for USP7 inhibitors to transform “immune desert” tumors into “immune responsive” tumors, this paves the way for a novel therapeutic strategy combining USP7 inhibitors with immune checkpoint inhibitors (ICIs).

Abstract A fundamental problem in plasma turbulence is understanding how energy cascades across multiple scales. In this paper, a new weak turbulence theory is developed to explain how energy can be transferred from Langmuir and Upper‐Hybrid waves to ion‐acoustic waves. A kinetic approach is used where the Boltzmann equation is Fourier‐Laplace transformed, and the nonlinear term is retained. A unique feature of this approach is the ability to calculate power spectra at low frequencies, for any wavelength or magnetic aspect angle. The results of this theory explain how the predominant type of 150‐km radar echoes are generated in the ionosphere. First, peaks in the suprathermal electron velocity distribution drive a bump‐on‐tail like instability that excites the Upper‐Hybrid mode. This excited wave then couples nonlinearly to the ion‐acoustic mode, generating the ∼10 dB enhancement observed by radars. This theory also explains why higher frequency radars like ALTAIR do not observe these echoes.

Abstract Background Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence. Methods Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis. Results Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1–16.1] in patients with poor adherence compared to 5.8% [5.0–6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8–2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3–15.2] in patients with poor adherence and 4.9% [4.1–5.8] in patients with full adherence; p

The microbial ecology of agricultural products may provide crucial insights into the management of postharvest fruit rots. To investigate postharvest microbial communities of highbush blueberry (Vaccinium corymbosum), five fungicide spray programs were evaluated for their influence on the mycobiome of fruit skin and within the fruit pulp. The mycobiome was characterized by sequencing amplicons of the internal transcribed spacer 1 (ITS1) region with primers ITS1f and ITS4 with the Illumina MiSeq 300bp v3 system. Two of the five programs utilized commercial biological fungicides, two utilized azoxystrobin, and one utilized a series of treatments to simulate a realistic disease management program. Fungicide applications reduced diversity of the fruit skin mycobiome (R2 = 0.409, P = 0.0001) and had a moderate impact on the pulp mycobiome (R2 = 0.233, P = 0.0001). The mycobiome of the fruit pulp was also more variable than the skin mycobiome. In comparison with the untreated controls, each fungicide treatment program had a strongly significant effect on the β diversity of the blueberry fruit skin mycobiome (R2 = 0.53 to 0.73, P = 0.0001). In the pulp, three of the five treatments had moderate but significant effects on β diversity in comparison with the control (R2 = 0.10 to 0.18, P = 0.0005 to 0.017). Most samples indicated that fungi belonging to genera Epicoccum, Papiliotrema, and Sporobolomyces were widely prevalent and abundant across treatments and tissues. Fruit pathogen Botrytis cinerea was particularly abundant in the pulp of three of the fungicide treatments. Results from this study provide a baseline for future exploration of postharvest rot pathology and provide a community context on how fungicides may alter fungal communities in agricultural systems.

Abstract Diverse members of early-diverging Mucoromycota, including mycorrhizal taxa and soil-associated Mortierellaceae, are known to harbor Mollicutes-related endobacteria (MRE). It has been hypothesized that MRE were acquired by a common ancestor and transmitted vertically. Alternatively, MRE endosymbionts could have invaded after the divergence of Mucoromycota lineages and subsequently spread to new hosts horizontally. To better understand the evolutionary history of MRE symbionts, we generated and analyzed four complete MRE genomes from two Mortierellaceae genera: Linnemannia (MRE-L) and Benniella (MRE-B). These genomes include the smallest known of fungal endosymbionts and showed signals of a tight relationship with hosts including a reduced functional capacity and genes transferred from fungal hosts to MRE. Phylogenetic reconstruction including nine MRE from mycorrhizal fungi revealed that MRE-B genomes are more closely related to MRE from Glomeromycotina than MRE-L from the same host family. We posit that reductions in genome size, GC content, pseudogene content, and repeat content in MRE-L may reflect a longer-term relationship with their fungal hosts. These data indicate Linnemannia and Benniella MRE were likely acquired independently after their fungal hosts diverged from a common ancestor. This work expands upon foundational knowledge on minimal genomes and provides insights into the evolution of bacterial endosymbionts.

Abstract As microbiome research has progressed, it has become clear that most, if not all, eukaryotic organisms are hosts to microbiomes composed of prokaryotes, other eukaryotes, and viruses. Fungi have only recently been considered holobionts with their own microbiomes, as filamentous fungi have been found to harbor bacteria (including cyanobacteria), mycoviruses, other fungi, and whole algal cells within their hyphae. Constituents of this complex endohyphal microbiome have been interrogated using multi-omic approaches. However, a lack of tools, techniques, and standardization for integrative multi-omics for small-scale microbiomes (e.g., intracellular microbiomes) has limited progress towards investigating and understanding the total diversity of the endohyphal microbiome and its functional impacts on fungal hosts. Understanding microbiome impacts on fungal hosts will advance explorations of how “microbiomes within microbiomes” affect broader microbial community dynamics and ecological functions. Progress to date as well as ongoing challenges of performing integrative multi-omics on the endohyphal microbiome is discussed herein. Addressing the challenges associated with the sample extraction, sample preparation, multi-omic data generation, and multi-omic data analysis and integration will help advance current knowledge of the endohyphal microbiome and provide a road map for shrinking microbiome investigations to smaller scales. Video Abstract

Land use regression (LUR) models are widely used in epidemiological and environmental studies to estimate humans’ exposure to air pollution within urban areas. However, the early models, developed using linear regressions and data from fixed monitoring stations and passive sampling, were primarily designed to model traditional and criteria air pollutants and had limitations in capturing high-resolution spatiotemporal variations of air pollution. Over the past decade, there has been a notable development of multi-source observations from low-cost monitors, mobile monitoring, and satellites, in conjunction with the integration of advanced statistical methods and spatially and temporally dynamic predictors, which have facilitated significant expansion and advancement of LUR approaches. This paper reviews and synthesizes the recent advances in LUR approaches from the perspectives of the changes in air quality data acquisition, novel predictor variables, advances in model-developing approaches, improvements in validation methods, model transferability, and modeling software as reported in 155 LUR studies published between 2011 and 2023. We demonstrate that these developments have enabled LUR models to be developed for larger study areas and encompass a wider range of criteria and unregulated air pollutants. LUR models in the conventional spatial structure have been complemented by more complex spatiotemporal structures. Compared with linear models, advanced statistical methods yield better predictions when handling data with complex relationships and interactions. Finally, this study explores new developments, identifies potential pathways for further breakthroughs in LUR methodologies, and proposes future research directions. In this context, LUR approaches have the potential to make a significant contribution to future efforts to model the patterns of long- and short-term exposure of urban populations to air pollution.