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ErbB3, a member of the ErbB family of receptor tyrosine kinases, is a potent activator of phosphatidyl inositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling, driving tumor cell survival and therapeutic resistance in breast cancers. In luminal breast cancers, ErbB3 upregulation following treatment with the antiestrogen fulvestrant enhances PI3K/mTOR-mediated cell survival. However, the mechanism by which ErbB3 is upregulated in fulvestrant-treated cells is unknown. We found that ErbB3 protein levels and cell surface presentation were increased following fulvestrant treatment, focusing our attention on proteins that regulate ErbB3 at the cell surface, including Nrdp1, NEDD4 and LRIG1. Among these, only LRIG1 correlated positively with ERα, but inversely with ErbB3 in clinical breast cancer data sets. LRIG1, an estrogen-inducible ErbB downregulator, was decreased in a panel of fulvestrant-treated luminal breast cancer cells. Ectopic LRIG1 expression from an estrogen-independent promoter uncoupled LRIG1 from estrogen regulation, thus sustaining LRIG1 and maintaining low ErbB3 levels in fulvestrant-treated cells. An LRIG1 mutant lacking the ErbB3 interaction motif was insufficient to downregulate ErbB3. Importantly, LRIG1 overexpression improved fulvestrant-mediated growth inhibition, whereas cells expressing the LRIG1 mutant were poorly sensitive to fulvestrant, despite effective ERα downregulation. Consistent with these results, LRIG1 expression correlated positively with increased disease-free survival in antiestrogen-treated breast cancer patients. These data suggest that ERα-dependent expression of LRIG1 dampens ErbB3 signaling in luminal breast cancer cells, and by blocking ERα activity with fulvestrant, LRIG1 is decreased thus permitting ErbB3 accumulation, enhanced ErbB3 signaling to cell survival pathways and blunting therapeutic response to fulvestrant.

The rapid growth of the elderly population coupled with research demonstrating the existence of ageist stereotypes even among very young children have led to the rise of intergenerational programs. Very limited research has been conducted, however, to demonstrate the effectiveness of these programs in producing attitudinal change or other beneficial outcomes for at-risk children. This study examined the impact of an intergenerational program on children's attitudes toward elders and on their school-based behaviors. Eighty-one 4th grade children enrolled in an inner-city school participated in the study. Forty-one children, with matched seniors partners, engaged in activities based on the 4th grade core curriculum within an outdoor classroom environment while the remaining 40 children participated in usual core curriculum activities. At the conclusion of the program those children who participated in the program had significantly more positive attitudes towards the elderly and significantly better school behavioral grades than did non-participating students. Implications and recommendations for intergenerational programming are discussed. [ABSTRACT FROM AUTHOR]

The rapid growth of the elderly population coupled with research demonstrating the existence of ageist stereotypes even among very young children have led to the rise of intergenerational programs. Very limited research has been conducted, however, to demonstrate the effectiveness of these programs in producing attitudinal change or other beneficial outcomes for at-risk children. This study examined the impact of an intergenerational program on children's attitudes toward elders and on their school-based behaviors. Eighty-one 4th grade children enrolled in an inner-city school participated in the study. Forty-one children, with matched seniors partners, engaged in activities based on the 4th grade core curriculum within an outdoor classroom environment, while the remaining 40 children participated in usual core curriculum activities. At the conclusion of the program those children who participated in the program had significantly more positive attitudes towards the elderly and significantly better school behavioral grades than did non-participating students. Implications and recommendations for intergenerational programming are discussed. [ABSTRACT FROM AUTHOR]

The purposes of this research were to describe the accuracy of test-weighing with the BabyWeigh, a new infant scale suitable for use in the home, and to determine whether mothers and investigators could estimate intake accurately during breastfeeding sessions, using clinical cues that are recommended for this purpose. Within five days of projected NICU discharge, 30 preterm and/or high risk infants and their mothers were studied during a single breastfeeding session. A member of the research team performed test-weights with the Smart Model l20 infant scale, and mothers performed test-weights with the BabyWeigh scale. The mothers and investigators each estimated volume of intake for the breastfeeding session using clinical cues. Mothers and investigators were blind to each others' test-weights and clinical estimates. Results revealed that the BabyWeigh scale provided an accurate estimate of intake during breastfeeding across a large range of infant weights and intake volumes. In contrast, investigator and maternal estimates of intake were not sufficiently accurate. [ABSTRACT FROM AUTHOR]

African Americans experience a greater risk of Alzheimer disease (AD), but are underrepresented in AD research. Our study examined barriers and facilitators of AD research participation among African Americans. Investigators conducted 11 focus groups with African American participants (n=70) who discussed barriers and facilitators to AD research participation including lumbar puncture studies. The moderator and comoderator independently reviewed the transcripts, identified themes, and coded transcripts for analysis. Participants were predominately female (73%) with a mean age of 52 years (range 21 to 86 y). Concerns and attitudes were consistent across education, socioeconomic status, and sex. Mistrust was a fundamental reason for nonparticipation. Additional barriers included insufficient information dissemination in the African American community, inconvenience, and reputation of the researcher and research institution. Barriers to participation in AD biomarker studies were fear of the unknown and adverse effects. Altruism and relevance of research projects to the individual, family members, or the African American community facilitate participation. Increased participation results from relationships with the community that extend beyond immediate research interests, dissemination of research findings, and emphasis on relevance of proposed studies. Pervasive barriers impede African American participation in AD research but can be overcome through a sustained presence in the community. [ABSTRACT FROM AUTHOR]

Significance: TDO2 is more highly expressed than the nonhomologous TRP-catabolizing enzyme IDO1 in TNBC. We find that TDO2 knockdown can lead to a compensatory increase in IDO1. Therefore, we tested a newly developed TDO2/IDO1 dual inhibitor and found that it decreases TRP catabolism, anchorage-independent survival, and invasive capacity., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Compared with the operating room, tracheal intubations in the intensive care unit (ICU) are associated with worsened glottic view, decreased first-time success rate and increase in the technical difficulty of intubation and incidence of complications. Videolaryngoscopes (VLs) have been proposed to improve airway management, and while recent studies have confirmed that VLs improve intubation conditions in this patient population, there remains a lack of clarity regarding the selection between a standard Macintosh blade or a hyperangulated one, to determine which yields the best outcomes. The purpose of this study was to compare successful intubation on the first attempt with the Macintosh VL versus the hyperangulated VL during tracheal intubation in ICU patients. We hypothesise that tracheal intubation using the hyperangulated VL will improve the frequency of successful intubation on the first attempt., Methods and Analysis: The INtubation VIdeolaryngoscopy BLADE-ICU trial is a prospective, multicentre, open-label, interventional, randomised, controlled superiority study conducted in 29 ICUs in Spain. Patients will be randomly assigned in a 1:1 ratio to undergo intubation using a Macintosh VL (control group) or a hyperangulated VL (experimental group) for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcomes include the time to intubation, attempts for successful intubation, laryngoscopic vision assessed with the modified Cormack-Lehane scale, the need for adjuvant airway devices for intubation, difficulty assessed by the anaesthesiologist and complications during tracheal intubation. Enrolment began on 1 May 2024 and is expected to be completed in 2025., Ethics and Dissemination: The study protocol was approved on 29 February 2024, by the Ethics Committee of Galicia (CEImG, code No. 2024-031).The results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: NCT06322719., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To characterize the diagnostic yield of patients undergoing evaluation for superior canal dehiscence syndrome (SCDS), and identify alternative conditions diagnosed in patients suspected of, but not ultimately diagnosed with, SCDS., Methods: Diagnostically undifferentiated adult patients suspected of having SCDS were identified between 2016 and 2021 at a tertiary academic medical system. Patients were categorized by diagnostic testing, radiographic superior semicircular canal (SSC) abnormality, symptoms, evaluating clinician specialty, operative intervention, and diagnosis. Differences among groups were assessed for statistical significance., Results: Of 1242 candidate patients, 477 met inclusion criteria-evaluation by a clinician with SCDS on their differential diagnosis prior to diagnostic imaging. The mean (SD) age was 53.0 (15.0) years and 70.6% were female. A total of 364 patients underwent subsequent diagnostic imaging, and among these, 164 (45.1%) had a radiographic SSC abnormality with 99 (27.2%) receiving a diagnosis of SCDS (two cases of "near dehiscence syndrome"). One third (33.3%) of patients with SCDS underwent operative repair. Most clinicians with the initial suspicion for SCDS were otolaryngologists (90.6%), who had greater diagnostic yield than clinicians from other specialties (22.2% vs. 6.7%, p = 0.012). Patients not diagnosed with SCDS alternatively received 21 unique diagnoses and 52.1% (138/265) were not definitively diagnosed with any condition., Conclusions: This study characterizes the diagnostic incidence, or yield, of newly identified radiographic SSC abnormalities (45.1%) and SCDS (27.2%) among people suspected of having SCDS. Considerable overlap in presentation between SCDS and other conditions exists, and there is need for improvement in efficiently diagnosing patients with SCDS and audio-vestibular complaints in general., Level of Evidence: III Laryngoscope, 134:4095-4100, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

This study investigates whether systems-level interventions, specifically patient-centered culturally sensitive health care (PC-CSHC) from healthcare providers, office staff, and the clinic environment, moderate the relationship between health self-efficacy and patient engagement among Black American adults. An online survey was completed by 198 Black American adults. PC-CSHC from healthcare providers, office staff, and the clinic environment did not mitigate the adverse effects of low health self-efficacy on patient engagement. However, PC-CSHC from healthcare providers (b = 0.38) was as significant as health self-efficacy (b = 0.37) in predicting patient engagement, R 2  = 0.47, F(9, 177) = 19.61, p < 0.001. Provider-delivered PC-CSHC can enhance patient engagement among Black American adults. This systems-level approach has the potential to reach more patients than intrapersonal interventions alone and alleviates the undue burden placed on Black Americans to leverage intrapersonal strengths in the face of health disparities rooted in structural racism., (© 2024 The Author(s). Journal of Community Psychology published by Wiley Periodicals LLC.)

Aims: The longitudinal programme of research described in this paper seeks to generate knowledge about factors influencing the implementation of a system-level intervention, the clinical nurse leader care model, involving nurses as leaders at the frontlines of care and the outcomes achievable with successful implementation. The research programme has the following aims, (a) to clarify clinical nurse leader practice, (b) develop and empirically validate a translational model of frontline care delivery that includes clinical nurse leader practice and (c) delineate the patterns of and critical outcomes of successful implementation of the clinical nurse leader care model., Design: This programme of research follows a knowledge-building trajectory involving multiple study designs in both qualitative (grounded theory, case study) and quantitative (descriptive, correlational and quasi-experimental) traditions., Methods: Multiple mixed methods within a system-based participatory framework were used to conduct this programme of implementation-effectiveness research., Results: Findings are demonstrating how the clinical nurse leader care model, as a complex system-level intervention, can be implemented in diverse healthcare contexts to make a difference to patient care quality and safety. Findings also contribute to implementation science, helping to better understand the dynamic interdependencies between implementation, the interventions implemented and the contexts in which they are implemented., Conclusion: Findings translate into sets of evidence-informed implementation 'recipes' that health systems can match to their specific contexts and needs. This allows health systems to take on strategies that both maximize resource impact within their existing structures and support achieving intended outcomes., Implication: This programme of research is producing actionable implementation and outcome evidence about ways to organize nursing knowledge and practice into care models that can be successfully adopted within real-world healthcare settings to achieve safer and higher quality patient care., (© 2024 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Introduction: Effective weed management tools are crucial for maintaining the profitable production of snap bean ( Phaseolus vulgaris L.). Preemergence herbicides help the crop to gain a size advantage over the weeds, but the few preemergence herbicides registered in snap bean have poor waterhemp (Amaranthus tuberculatus) control, a major pest in snap bean production. Waterhemp and other difficult-to-control weeds can be managed by flumioxazin, an herbicide that inhibits protoporphyrinogen oxidase (PPO). However, there is limited knowledge about crop tolerance to this herbicide. We aimed to quantify the degree of snap bean tolerance to flumioxazin and explore the underlying mechanisms., Methods: We investigated the genetic basis of herbicide tolerance using genome-wide association mapping approach utilizing field-collected data from a snap bean diversity panel, combined with gene expression data of cultivars with contrasting response. The response to a preemergence application of flumioxazin was measured by assessing plant population density and shoot biomass variables., Results: Snap bean tolerance to flumioxazin is associated with a single genomic location in chromosome 02. Tolerance is influenced by several factors, including those that are indirectly affected by seed size/weight and those that directly impact the herbicide's metabolism and protect the cell from reactive oxygen species-induced damage. Transcriptional profiling and co-expression network analysis identified biological pathways likely involved in flumioxazin tolerance, including oxidoreductase processes and programmed cell death. Transcriptional regulation of genes involved in those processes is possibly orchestrated by a transcription factor located in the region identified in the GWAS analysis. Several entries belonging to the Romano class, including Bush Romano 350, Roma II, and Romano Purpiat presented high levels of tolerance in this study. The alleles identified in the diversity panel that condition snap bean tolerance to flumioxazin shed light on a novel mechanism of herbicide tolerance and can be used in crop improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saballos, Brooks, Tranel and Williams.)

Introduction: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study., Methods: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop., Results: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective., Discussion: The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease-modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation., Highlights: Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers.Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement.Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation.Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Whole-genome sequencing (WGS) of microbial pathogens recovered from patients with infectious disease facilitates high-resolution strain characterization and molecular epidemiology. However, increasing reliance on culture-independent methods to diagnose infectious diseases has resulted in few isolates available for WGS. Here, we report a novel culture-independent approach to genome characterization of Bordetella pertussis , the causative agent of pertussis and a paradigm for insufficient genomic surveillance due to limited culture of clinical isolates. Sequencing libraries constructed directly from residual pertussis-positive diagnostic nasopharyngeal specimens were hybridized with biotinylated RNA "baits" targeting B. pertussis fragments within complex mixtures that contained high concentrations of host and microbial background DNA. Recovery of B. pertussis genome sequence data was evaluated with mock and pooled negative clinical specimens spiked with reducing concentrations of either purified DNA or inactivated cells. Targeted enrichment increased the yield of B. pertussis sequencing reads up to 90% while simultaneously decreasing host reads to less than 10%. Filtered sequencing reads provided sufficient genome coverage to perform characterization via whole-genome single nucleotide polymorphisms and whole-genome multilocus sequencing typing. Moreover, these data were concordant with sequenced isolates recovered from the same specimens such that phylogenetic reconstructions from either consistently clustered the same putatively linked cases. The optimized protocol is suitable for nasopharyngeal specimens with diagnostic IS 481 Ct < 35 and >10 ng DNA. Routine implementation of these methods could strengthen surveillance and study of pertussis resurgence by capturing additional cases with genomic characterization., Competing Interests: The authors declare no conflict of interest.

Background: Tolpyralate, a relatively new inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), is registered for postemergence use in all types of corn (Zea mays L.) and has a record of excellent crop tolerance. A report of severe crop injury to sweet corn inbred (XSEN187) led to the following objectives: (i) determine whether sensitivity to tolpyralate in XSEN187 exists, and if confirmed, (ii) determine the genetic basis of tolpyralate sensitivity, and (iii) screen other corn germplasm for sensitivity to tolpyralate., Results: Inbred XSEN187 was confirmed sensitive to tolpyralate. Inclusion of methylated seed oil or nonionic surfactant in the spray volume was necessary for severe crop injury. Tolpyralate sensitivity in XSEN187 is not conferred by alleles at Nsf1, a cytochrome P450-encoding gene (CYP81A9) conferring tolerance to many corn herbicides. Evidence suggests that tolpyralate sensitivity in XSEN187 is conferred by a single gene mapped to the Chr05: 283 240-1 222 909 bp interval. Moreover, tolpyralate sensitivity was observed in 48 other sweet corn and field corn inbreds., Conclusions: Severe sensitivity to tolpyralate exists in sweet corn and field corn germplasm when the herbicide is applied according to label directions. Whereas the corn response to several other herbicides, including HPPD-inhibitors, is conferred by the Nsf1 locus, corn sensitivity to tolpyralate is the result of a different locus. The use of tolpyralate should consider herbicide tolerance in inbred lines from which corn hybrids were derived, whereas alleles that render corn germplasm sensitive to tolpyralate should be eliminated from breeding populations, inbreds, and commercial cultivars. © 2023 Illinois Foundation Seeds, Inc and The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2023 Illinois Foundation Seeds, Inc and The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes. We developed and characterized cellular and mouse models, to replicate the genetic profile of a patient who is compound heterozygous for 2 ADAMTSL2 variants, namely p.R61H and p.A165T. The impairment of ADAMTSL2 secretion was observed in both variants, but p.A165T exhibited a more severe impact. Mice carrying different allelic combinations revealed a spectrum of phenotypic severity, from lethality in knockout homozygotes to mild growth impairment observed in adult p.R61H homozygotes. Homozygous and hemizygous p.A165T mice survived but displayed severe respiratory and cardiac dysfunction. The respiratory dysfunction mainly affected the expiration phase, and some of these animals had microscopic post-obstructive pneumonia. Echocardiograms and MRI studies revealed a significant systolic dysfunction, accompanied by a reduction of the aortic root size. Histology verified the presence of hypertrophic cardiomyopathy with myocyte hypertrophy, chondroid metaplasia, and mild interstitial fibrosis. This study revealed a substantial correlation between the degree of impaired ADAMTSL2 secretion and the severity of the observed phenotype in GD1.

Importance: Pertussis, caused by Bordetella pertussis , can cause debilitating respiratory symptoms, so whole-cell pertussis vaccines (wPVs) were introduced in the 1940s. However, reactogenicity of wPV necessitated the development of acellular pertussis vaccines (aPVs) that were introduced in the 1990s. Since then, until the COVID-19 pandemic began, reported pertussis incidence was increasing, suggesting that aPVs do not induce long-lasting immunity and may not effectively prevent transmission. Additionally, aPVs do not provide protection against other Bordetella species that are observed during outbreaks. The significance of this work is in determining potential new vaccine antigens for multiple Bordetella species that are predicted to elicit long-term immune responses. Genome-based approaches have aided the development of novel vaccines; here, these methods identified Bordetella vaccine candidates that may be cross-protective and predicted to induce strong memory responses. These targets can lead to an improved vaccine with a strong safety profile while also strengthening the longevity of the immune response., Competing Interests: The authors declare no conflict of interest.

Objective: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment., Methods: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time., Results: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression., Conclusions: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression., (Copyright © 2023. Published by Elsevier Inc.)

The rapid adoption of glyphosate-resistant crops at the end of the 20th century caused a simplification of weed management that relied heavily on glyphosate for weed control. However, the effectiveness of glyphosate has diminished. A greater understanding of trends related to glyphosate use will shed new light on weed adaptation to a product that transformed global agriculture. Objectives were to (1) quantify the change in weed control efficacy from postemergence (POST) glyphosate use on troublesome weeds in corn and soybean and (2) determine the extent to which glyphosate preceded by a preemergence (PRE) improved the efficacy and consistency of weed control compared to glyphosate alone. Herbicide evaluation trials from 24 institutions across the United States of America and Canada from 1996 to 2021 were compiled into a single database. Two subsets were created; one with glyphosate applied POST, and the other with a PRE herbicide followed by glyphosate applied POST. Within each subset, mean and variance of control ratings for seven problem weed species were regressed over time for nine US states and one Canadian province. Mean control with POST glyphosate alone decreased over time while variability in control increased. Glyphosate preceded by a labeled PRE herbicide showed little change in mean control or variability in control over time. These results illustrate the rapid adaptation of agronomically important weed species to the paradigm-shifting product glyphosate. Including more diversity in weed management systems is essential to slowing weed adaptation and prolonging the usefulness of existing and future technologies., (Published by Oxford University Press on behalf of National Academy of Sciences 2023.)

The Arthur and Sandra Irving Cancer Immunology Symposium has been created as a platform for established cancer immunologists to mentor trainees and young investigators as they launch their research career in the field. By sharing their different paths to success, the senior faculty mentors provide an invaluable resource to support the development of the next generation of leaders in the cancer immunology community. This Commentary describes some of the key topics that were discussed during the 2022 symposium: scientific and career trajectory, leadership, mentoring, collaborations, and publishing. For each of these topics, established investigators discussed the elements that facilitate success in these areas as well as mistakes that can hinder progress. Herein, we outline the critical points raised in these discussions for establishing a successful independent research career. These points are highly relevant for the broader scientific community., (©2023 The Authors; Published by the American Association for Cancer Research.)

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: By analyzing how health care leaders in the United States view mobile health programs and their impact on the organization's bottom line, this study equips those who currently operate or plan to deploy mobile clinics with a business case framework. Our aim is to understand health care leaders' perspectives about business-related incentives and disincentives for mobile healthcare., Methods: We conducted 25 semi-structured key informant interviews with U.S. health care leaders to explore their views and experiences related to mobile health care. We used deductive and inductive thematic analysis to identify patterns in the data. An advisory group with expertise in mobile health, health management, and health care finance informed data collection and analysis., Results: In addition to improving health outcomes, mobile clinics can bolster business objectives of health care organizations including those related to budget, business strategy, organizational culture, and health equity. We created a conceptual framework that demonstrates how these factors, supported by community engagement and data, come together to form a business case for mobile health care., Discussion: Our study demonstrates that mobile clinics can contribute to health care organizations' business goals by aligning with broader organizational strategies. The conceptual model provides a guide for aligning mobile clinics' work with business priorities of organizations and funders., Conclusions: By understanding how health care leaders reconcile the business pressures they face with opportunities to advance health equity using mobile clinics, we can better support the strategic and sustainable expansion of the mobile health sector., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Respiratory diphtheria is a serious infection caused by toxigenic Corynebacterium diphtheriae , and disease transmission mainly occurs through respiratory droplets. Between 2017 and 2019, a large diphtheria outbreak among forcibly displaced Myanmar nationals densely settled in Bangladesh was investigated. Here we utilized whole-genome sequencing (WGS) to characterize recovered isolates of C. diphtheriae and two co-circulating non-diphtheritic Corynebacterium (NDC) species - C. pseudodiphtheriticum and C. propinquum. C. diphtheriae isolates recovered from all 53 positive cases in this study were identified as toxigenic biovar mitis, exhibiting intermediate resistance to penicillin, and formed four phylogenetic clusters circulating among multiple refugee camps. Additional sequenced isolates collected from two patients showed co-colonization with non-toxigenic C. diphtheriae biovar gravis, one of which exhibited decreased susceptibility to the first-line antibiotics and harboured a novel 23-kb multidrug resistance plasmid. Results of phylogenetic reconstruction and virulence-related gene contents of the recovered NDC isolates indicated they were likely commensal organisms, though 80.4 %(45/56) were not susceptible to erythromycin, and most showed high minimum inhibition concentrations against azithromycin. These results demonstrate the high resolution with which WGS can aid molecular investigation of diphtheria outbreaks, through the quantification of bacterial genetic relatedness, as well as the detection of virulence factors and antibiotic resistance markers among case isolates.

Field measurements of Rn-222 fluxes from the tops and bottoms of compacted clay radon barriers were used to calculate effective Rn diffusion coefficients (D Rn ) at four uranium waste disposal sites in the western United States to assess cover performance after more than 20 years of service. Values of D Rn ranged from 7.4 × 10 -7 to 6.0 × 10 -9  m 2 /s, averaging 1.42 × 10 -7 . Water saturation (S W ) from soil cores indicated that there was relatively little control of D Rn by S W , especially at higher moisture levels, in contrast to estimates from most steady-state diffusion models. This is attributed to preferential pathways intrinsic to construction of the barriers or to natural process that have developed over time including desiccation cracks, root channels, and insect burrows in the engineered earthen barriers. A modification to some models in which fast and slow pathway D Rn values are partitioned appears to give a good representation of the data; 4% of the fast pathway was needed to fit the data regression. For locations with high S w and highest D Rn (and fluxes) at each site, the proportion of fast pathway ranged from 1.7% to 34%, but for many locations with lower fluxes, little if any fast pathway was needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Disadvantage in early childhood (ages 0-5 years) is associated with worse health and educational outcomes in adolescence. Evidence on the clustering of these adverse outcomes by household income is scarce in the generation of adolescents born since the turn of the millennium. We aimed to describe the association between household income in early childhood and physical health, psychological distress, smoking behaviour, obesity, and educational outcomes at age 17 years, including the patterning and clustering of these five outcomes by income quintiles., Methods: In this population-based, retrospective cohort study, we used data from the Millennium Cohort Study in which individuals born in the UK between Sept 1, 2000, and Jan 1, 2002, were followed up. We collected data on five adverse health and social outcomes in adolescents aged 17 years known to limit life chances: psychological distress, self-assessed ill health, smoking, obesity, and poor educational achievement. We compared how single and multiple outcomes were distributed across early childhood quintile groups of income, as an indicator of disadvantage, and modelled the potential effect of three income-shifting scenarios in early childhood for reducing adverse outcomes in adolescence., Findings: We included 15 245 adolescents aged 17 years, 7788 (51·1%) of whom were male and 7457 (48·9%) of whom were female. Adolescents in the lowest income quintile group in childhood were 12·7 (95% CI 6·4-25·1) times more likely than those in the highest quintile group to have four or five adverse adolescent outcomes, with poor educational achievement (risk ratio [RR] 4·6, 95% CI 4·2-5·0) and smoking (3·6, 3·0-4·2), showing the largest single risk ratios. Shifting up to the second lowest, middle, and highest income groups would reduce multiple adolescent adversities by 4·9% (95% CI -23·8 to 33·6), 32·3% (-2·7 to 67·3), and 83·9% (47·2 to 120·7), respectively. Adjusting for parental education and single parent status moderately attenuated these estimates., Interpretation: Early childhood disadvantage is more strongly correlated with multiple adolescent adversities than any of the five single adverse outcomes. However, shifting children from the lowest income quintile group to the next lowest group is ineffective. Tackling multiple adolescent adversities requires managing early childhood disadvantage across the social gradient, with income redistribution as a central element of coordinated cross-sectoral action., Funding: UK Prevention Research Partnership., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licence. Published by Elsevier Ltd.. All rights reserved.)

Diffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss of H3K27 trimethylation, but lacking the canonical H3K27M mutation (H3-WT). Here, we report a cohort of five H3-WT tumours profiled by whole-genome sequencing, RNA sequencing and DNA methylation profiling and combine their analysis with previously published cases. We show that these tumours have recurrent and mutually exclusive mutations in either ACVR1 or EGFR and are characterised by high expression of EZHIP associated to its promoter hypomethylation. Affected patients share a similar poor prognosis as patients with H3K27M DMG. Global molecular analysis of H3-WT and H3K27M DMG reveal distinct transcriptome and methylome profiles including differential methylation of homeobox genes involved in development and cellular differentiation. Patients have distinct clinical features, with a trend demonstrating ACVR1 mutations occurring in H3-WT tumours at an older age. This in-depth exploration of H3-WT tumours further characterises this novel DMG, H3K27-altered sub-group, characterised by a specific immunohistochemistry profile with H3K27me3 loss, wild-type H3K27M and positive EZHIP. It also gives new insights into the possible mechanism and pathway regulation in these tumours, potentially opening new therapeutic avenues for these tumours which have no known effective treatment. This study has been retrospectively registered on clinicaltrial.gov on 8 November 2017 under the registration number NCT03336931 ( https://clinicaltrials.gov/ct2/show/NCT03336931 )., (© 2023. The Author(s).)

Metastatic cancer is difficult to treat and is responsible for the majority of cancer-related deaths. After cancer cells initiate metastasis and successfully seed a distant site, resident cells in the tissue play a key role in determining how metastatic progression develops. The lung is the second most frequent site of metastatic spread, and the primary site of metastasis within the lung is alveoli. The most abundant cell type in the alveolar niche is the epithelium. This review will examine the potential contributions of the alveolar epithelium to metastatic progression. It will also provide insight into other ways in which alveolar epithelial cells, acting as immune sentinels within the lung, may influence metastatic progression through their various interactions with cells in the surrounding microenvironment.

Introduction: We examined baseline differences in depression and antidepressant use among cognitively normal older adults in five ethnoracial groups and assessed whether depression predicted a faster progression to incident cognitive impairment across groups., Methods: Data from the National Alzheimer's Coordinating Center (n = 8168) were used to examine differences between non-Hispanic Whites (nHW), African Americans (AA), Hispanics, Asians, and American Indian and Alaskan Natives in cross-sectional and longitudinal models., Results: AA had a lower risk of depression compared to nHW at baseline. No statistical interactions were noted between ethnoracial groups and depression. However, depression independently predicted a faster progression to incident cognitive impairment. Hispanics and Asian participants had a higher hazard for progression compared to nHW., Discussion: Previously established risk factors between depression and dementia were not found among AA and nHW participants. The relationship between depression and ethnoracial groups is complex and suggests differential effects on progression from cognitive normality to impairment., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

N6-methyladenosine (m6A) modification of RNA regulates normal and cancer biology, but knowledge of its function on long noncoding RNAs (lncRNAs) remains limited. Here, we reveal that m6A regulates the breast cancer-associated human lncRNA HOTAIR. Mapping m6A in breast cancer cell lines, we identify multiple m6A sites on HOTAIR, with 1 single consistently methylated site (A783) that is critical for HOTAIR-driven proliferation and invasion of triple-negative breast cancer (TNBC) cells. Methylated A783 interacts with the m6A "reader" YTHDC1, promoting chromatin association of HOTAIR, proliferation and invasion of TNBC cells, and gene repression. A783U mutant HOTAIR induces a unique antitumor gene expression profile and displays loss-of-function and antimorph behaviors by impairing and, in some cases, causing opposite gene expression changes induced by wild-type (WT) HOTAIR. Our work demonstrates how modification of 1 base in an lncRNA can elicit a distinct gene regulation mechanism and drive cancer-associated phenotypes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.M.J., A.M.P., and J.T.R are listed as co-inventors on a patent application related to this work (U.S. 63/187,835)., (Copyright: © 2022 Porman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The homeless population in the United States is rapidly aging, with a parallel increase in Alzheimer's disease and related dementia (ADRD). During an evolving pandemic that jeopardizes employment and housing, assessing the relationship between ADRD and homelessness is critical since the latter is potentially intervenable. The objective of this study is to review the literature and determine whether there is an association between homelessness and dementia risk. A systematic review of existing studies was conducted through PubMED, SCOPUS, and EMBASE among others. Of the 228 results found, nine met inclusion criteria. Homeless studies mainly centered on veteran populations ( n = 6/9). There is a complex relationship suggesting homelessness as a risk for and consequence of ADRD but also co-occurrence with psychiatric disorders, substance abuse, and traumatic injuries. Future studies should employ enumeration surveys with modular longitudinal tracking and measure social determinants of health, discrimination, chronic stress, and mood disorders.

Crop production is sensitive to anomalous weather conditions, but vegetable crops can be highly sensitive to environmental changes. Using sweet corn data collected on 16,040 fields over a 27-year period, we: (a) estimate yield sensitivities to changes in growing season temperature and total precipitation, (b) estimate critical thresholds in non-linear temperature effects on sweet corn yield across diverse environments, and (c) quantify yield losses from surpassing the upper temperature threshold during anthesis in sweet corn. Our results show growing-season temperatures exceeding 30 [Formula: see text] were detrimental to crop yield. Each additional degree day spent above 30 [Formula: see text] during anthesis reduced crop yields by 0.5% and 2% in irrigated and rainfed fields, respectively. This study shows evidence for sweet corn yield losses across broad spatial domains in the wake of climate change and underscores the urgency to accelerate crop adaptation strategies to sustain production of this highly popular crop., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This report describes the complete genome sequences of four isolates of the nondiphtheritic Corynebacterium (NDC) species Corynebacterium pseudodiphtheriticum and Corynebacterium propinquum, recovered during investigation of a large diphtheria outbreak in Bangladesh. These data will assist in better delineating the boundary between these related species and understanding their virulence potential.

Antigenic differences formed by alterations in gene expression and alternative splicing are predicted in breast cancer cells undergoing epithelial to mesenchymal transition (EMT) and the reverse plasticity known as MET. How these antigenic differences impact immune interactions and the degree to which they can be exploited to enhance immune responses against mesenchymal cells is not fully understood. We utilized a master microRNA regulator of EMT to alter mesenchymal-like EO771 mammary carcinoma cells to a more epithelial phenotype. A computational approach was used to identify neoantigens derived from the resultant differentially expressed somatic variants (SNV) and alternative splicing events (neojunctions). Using whole cell vaccines and peptide-based vaccines, we find superior cytotoxicity against the more-epithelial cells and explore the potential of neojunction-derived antigens to elicit T cell responses through experiments designed to validate the computationally predicted neoantigens. Overall, results identify EMT-associated splicing factors common to both mouse and human breast cancer cells as well as immunogenic SNV- and neojunction-derived neoantigens in mammary carcinoma cells.