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Objectives: Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high‐frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved. Methods: Single‐cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10). T cell receptor (TCR) sequences were interrogated via similarity network analysis to explore antigenic targets using the published algorithm: Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2). Results: The mucosal T cell repertoire in healthy control airways consisted of highly expressed T cell clones conserved across anatomic subsites (trachea, bronchi, bronchioles, and lung). In iSGS, high‐frequency clones were equally represented in both scar and adjacent non‐scar tissue. Significant differences in repertoire structure between iSGS scar and unaffected mucosa was observed, driven by unique low‐frequency clones. GLIPH2 results suggest low‐frequency clones share targets between multiple iSGS patients. Conclusion: Healthy airway mucosa has a highly conserved T cell repertoire across multiple anatomic subsites. Similarly, iSGS patients have highly expressed T cell clones present in both scar and unaffected mucosa. iSGS airway scar possesses an abundance of less highly expanded clones with predicted antigen targets shared between patients. Interrogation of these shared motifs suggests abundant adaptive immunity to viral targets in iSGS airway scar. These results provide insight into disease pathogenesis and illuminate new treatment strategies in iSGS. Level of Evidence: NA Laryngoscope, 134:3245–3252, 2024 [ABSTRACT FROM AUTHOR]

Objectives: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Given the observed immune cell infiltrate in SGS, we sought to test the hypothesis that SGS cases possessed a low diversity (highly clonal) adaptive immune response when compared with healthy controls. Methods: Single cell RNA sequencing (scRNA‐seq) of subglottic mucosal scar in iSGS (n = 24), iLTS (n = 8), and healthy controls (n = 7) was performed. T cell receptor (TCR) sequences were extracted, analyzed, and used to construct repertoire structure, compare diversity, interrogate overlap, and define antigenic targets using the Immunarch bioinformatics pipeline. Results: The proximal airway mucosa in health and disease are equally diverse via Hill framework quantitation (iSGS vs. iLTS vs. Control, p > 0.05). Repertoires do not significantly overlap between individuals (Morisita <0.02). Among iSGS patients, clonality of the TCR repertoire is driven by CD8+ T cells, and iSGS patients possess numerous TCRs targeting viral and intercellular pathogens. High frequency clonotypes do not map to known targets in public datasets. Conclusion: SGS cases do not possess a lower diversity adaptive immune infiltrate when compared with healthy controls. Interestingly, the TCR repertoire in both health and disease contains a restricted number of high frequency clonotypes that do not significantly overlap between individuals. The target of the high frequency clonotypes in health and disease remain unresolved. Level of Evidence: NA Laryngoscope, 134:1757–1764, 2024 [ABSTRACT FROM AUTHOR]

Summary: Obesity in children remains a major public health problem, with the current prevalence in youth ages 2–19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29–30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi‐disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize mucosal microbial shifts in patients with acute laryngeal injury (ALgI) after intubation. This cross‐sectional study included 20 patients with ALgI who underwent early endoscopic intervention with tissue culture, 20 patients with idiopathic subglottic stenosis (iSGS) who underwent tissue culture during the routine endoscopic intervention, and 3 control patients who underwent mucosal swab culture. 70% of the ALgI patients had a positive culture compared to 5% of the iSGS patients and none of the controls. The most identified microbes isolated from ALgI patients included Staphylococcus species in 30% and Streptococcus species in 25%. The high rate of pathologic bacterial infiltration into postintubation laryngeal wounds supports efforts to reduce bacterial colonization of endotracheal tubes and highlights the role of culture‐directed antibiotic therapy as a part of early intervention to improve outcomes for patients with ALgI. [ABSTRACT FROM AUTHOR]

Objectives: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive fibrosis of the upper airway. iSGS almost exclusively affects women; as a result, female hormones (estrogen and progesterone) have been proposed to participate in the pathogenesis of iSGS. Our aim was to localize cell‐specific gene expression of estrogen receptors (ESR1 and ESR2) and progesterone receptor (PGR) using an established iSGS single‐cell RNA sequencing (scRNAseq) cell atlas. Study Design: Ex vivo molecular study of airway scar and healthy mucosa from iSGS patients. Methods: An established scRNAseq atlas consisting of 25,974 individually sequenced cells from subglottic scar (n = 7) or matched unaffected mucosa (n = 3) in iSGS patients was interrogated for RNA expression of ESR1, ESR2, and PGR. Results were quantified and compared across cell subsets, then visualized using Uniform Manifold Approximation and Projection (UMAP). Confirmatory protein assessment of endocrine receptors in fibroblasts from iSGS patients (n = 5) was performed via flow cytometry. Results: The proximal airway mucosa in iSGS patients demonstrates differential expression of endocrine receptors (ESR1, ESR2, PGR). Within airway scar, endocrine receptors are primarily expressed by fibroblasts, immune cells, and endothelial cells. Fibroblasts show strong ESR1 and PGR expression, while immune cells possess RNA for both ESR1 and ESR2. Endothelial cells predominantly express ESR2. Epithelial cells in unaffected mucosa express all three receptors, which are all reduced in airway scar. Conclusions: scRNAseq data localized endocrine receptor expression to specific cell subsets. These results provide the foundation for future work interrogating how hormone‐dependent mechanisms promote, sustain, or participate in iSGS disease pathogenesis. Level of Evidence: NA; Basic science Laryngoscope, 133:3506–3511, 2023 [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long‐term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight‐loss maintenance, and systems‐level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight‐reduced state. [ABSTRACT FROM AUTHOR]

A novel terrain of health care is emerging in Kenya at the intersection of a cancer epidemic, expanding medical and health insurance markets, the continued evisceration of public health care, and a middle class that can raise funds from credit, loans, and social networks. As middle‐class cancer patients and their families navigate these landscapes, they find themselves vulnerable both to the "ordinary crisis" of public health care undermined by austerity and neglect, and to an extractive medical marketplace offering state‐of‐the‐art treatment that is just within, or just beyond, financial reach. To analyze this, I build on Lauren Berlant's concept of cruel optimism, which captures how precarity is not only grounded in economic realities but also tied to hopes and expectations that always remain unfulfilled, creating constant anxiety and exhaustion. Further, I examine the double binds of cancer treatment and the entanglements between medical, health, and economic precarities, as families are drawn into private health care while the state disinvests in public services. [ABSTRACT FROM AUTHOR]

Objectives: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Yet despite recent advances, the genetic basis of SGS remains poorly understood. We sought to identify candidate risk genes associated with an SGS phenotype, investigate their biological function, and identify the cell types enriched for their expression. Methods: The Online Mendelian Inheritance in Man (OMIM) database was queried for single gene variants associated with an SGS phenotype. The functional intersections and molecular roles of the identified genes were explored using pathway enrichment analysis (PEA) computational methods. Cellular localization of the candidate risk genes was measured via transcriptional quantification in an established single cell RNA sequencing (scRNA‐seq) atlas of the proximal airway. Results: Twenty genes associated with SGS phenotype were identified. PEA resulted in 24 significantly enriched terms including "cellular response to TGF‐β," "epithelial‐to‐mesenchymal transition," and "adherens junctions." Mapping the 20 candidate risk genes to the scRNA‐seq atlas found 3 (15%) genes were enriched in epithelial cells, 3 (15%) in fibroblasts, and 3 (15%) in endothelial cells. 11 (55%) genes were expressed ubiquitously among tissue types. Interestingly, immune cells were not significantly enriched for candidate risk genes. Conclusion: We identify and provide biologic context for 20 genes associated with fibrotic disease of the proximal airway and form the foundation for future detailed genetic study. Level of evidence: N/A Laryngoscope, 133:3049–3056, 2023 [ABSTRACT FROM AUTHOR]

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease—both with regards to symptoms and underlying causal mechanisms—and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic‐based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases—including psychiatric disorders and allergies—available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high‐throughput molecular technologies, together with large collections of health data and novel data‐driven approaches, offers promise toward improved individual health through precision medicine. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole‐brain, voxel‐based, multi‐tissue mega‐analytic approach, thereby extending our recent surface‐based region of interest findings on a nearly matching sample using a complementary methodological approach. T1‐weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel‐based morphometry. The effects of group, sex, group‐by‐sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group‐by‐sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group‐by‐sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo‐occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD. [ABSTRACT FROM AUTHOR]

Background: Bronchiolitis is a major cause of infant illness, with few known modifiable risk factors. Breast feeding may reduce risk of severe bronchiolitis, but the association of exclusive vs. partial breast feeding with severe bronchiolitis is unclear. Objective: To estimate the association of exclusive vs. partial breast feeding during ages 0–2.9 months with bronchiolitis hospitalisation during infancy. Methods: We conducted a case–control study as a secondary analysis of two prospective US cohorts in the Multicenter Airway Research Collaboration. Cases were enrolled in a 17‐centre study of infants hospitalised for bronchiolitis during 2011–2014 (n = 921). Controls were enrolled in a five‐centre study of healthy infants during 2013–2014 and 2017 (n = 719). Breast feeding history during ages 0–2.9 months was collected by parent interview. Among breastfed infants, the association of exclusive vs. partial breast feeding with odds of bronchiolitis hospitalisation was estimated using a multivariable logistic regression model adjusted for demographic variables, parental asthma history, and early‐life exposures. As a secondary analysis, we estimated the associations of exclusive, predominant, and occasional breast feeding vs. no breast feeding with the odds of bronchiolitis hospitalisation. Results: Among 1640 infants, the prevalence of exclusive breast feeding was 187/921 (20.3%) among cases and 275/719 (38.3%) among controls. Exclusive vs. partial breast feeding was associated with 48% reduced odds of bronchiolitis hospitalisation (adjusted odds ratio [OR] 0.52, 95% confidence interval [CI] 0.39, 0.69). In the secondary analysis, exclusive vs. no breast feeding was associated with 58% reduced odds of bronchiolitis hospitalisation (OR 0.42, 95% CI 0.23, 0.77), whereas predominant breast feeding (OR 0.77, 95% CI 0.37, 1.57) and occasional breast feeding (OR 0.98, 95% CI 0.57, 1.69) were not associated with meaningfully reduced odds of bronchiolitis hospitalisation. Conclusion: Exclusive breast feeding had a strong protective association against bronchiolitis hospitalisation. [ABSTRACT FROM AUTHOR]

Ecological restoration, which encompasses habitat restoration and creation is essential to "bend the curve of biodiversity loss." However, well‐intentioned actions could alter plant pest/pathogen distributions resulting in unanticipated detrimental impacts on both host plants and associated biodiversity. Awareness among practitioners of this risk is unknown but likely to be limited. Using an online survey, with responses from 224 participants involved in ecological restoration in the United Kingdom, we assessed: (1) their awareness of plant health biosecurity risks; (2) whether they had risk assessments and biosecurity guidance/best practices for plant pests/pathogens; and (3) what, if any, new guidance was required. Participants perceived that their neighbors' activities, rather than their own, were the most likely source of pests/pathogens establishing. Their perceptions of the activities most likely to be a source of pests/pathogens did not match the literature, with the introduction of both mature plants and seeds viewed as the same level of risk. Over half the participants did not have a risk assessment for plant pests/pathogens. More of the participants (70%) had biosecurity guidance. However, of those participants that had biosecurity guidance 22% failed to check whether this guidance was followed, while 40% did not have anyone in their organization responsible for biosecurity. The most frequent requests from participants for guidance were: (1) what biosecurity to put in place for staff/contractors?; (2) the current legislation on plant pests/pathogens and movement of plants/soil/equipment. We conclude that risk assessments for plant pests/pathogens must become standard practice in ecological restoration. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to assess the utility of neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) in predicting radiographic sacroiliitis and active disease in axial spondyloarthritis (SpA) and to explore the association between use of a tumor necrosis factor inhibitor (TNFi) and these laboratory values compared with traditional inflammatory markers. Methods: Observational data from the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry were analyzed. We generated receiver operating characteristic curves to calculate laboratory cutoff values; we used these values in multivariable logistic regression models to identify associations with radiographically confirmed sacroiliitis and active disease. We also used logistic regression to determine the likelihood of elevated laboratory values after initiation of TNFi. Results: Most study participants (n = 354) were White, male, and HLA–B27 positive. NLR (odds ratio [OR] 1.459, P = 0.034), PLR (OR 4.842, P < 0.001), erythrocyte sedimentation rate (OR 4.397, P < 0.001), and C‐reactive protein (CRP) level (OR 2.911, P = 0.001) were independent predictors of radiographic sacroiliitis. Models that included PLR with traditional biomarkers performed better than those with traditional biomarkers alone. NLR (OR 6.931, P = 0.002) and CRP (OR 2.678, P = 0.004) were predictors of active disease, but the model that included both NLR and CRP performed better than CRP alone. TNFi use reduced the odds of elevated NLR (OR 0.172, P < 0.001), PLR (OR 0.073, P < 0.001), erythrocyte sedimentation rate (OR 0.319, P < 0.001), and CRP (OR 0.407, P < 0.001), but models that included NLR or PLR and traditional biomarkers performed best. Conclusions: These findings demonstrate an association between NLR and PLR and sacroiliitis and disease activity, with NLR and PLR showing response after TNFi treatment and adding useful clinical information to established biomarkers, thus perhaps assisting in management of axial SpA. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add‐on sessions of HF‐rTMS over the right dorsolateral pre‐frontal cortex (DLPFC) on alcohol use and craving. Design: Single‐center, single blind sham‐controlled parallel‐group RCT (n = 80), with 3 and 6 months follow‐up. Setting: Clinical treatment center in Amsterdam, the Netherlands. Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention: Ten sessions of active or sham HF‐rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work‐days. Measurements The primary outcome measure is the number of abstinent days over 6‐month follow‐up (FU). Secondary outcome measures are craving over 6‐month FU (alcohol urge questionnaire and obsessive‐compulsive drinking scale), time to first relapse over 6‐month FU and grams of alcohol consumed over 6‐month FU. Additional outcome measures: full abstinence over 6‐month FU and treatment success over 12‐month FU. Findings HF‐rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578–3.547]. Moreover, HF‐rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/−0.53, 95% CI mixed‐effects model = −9.14 to 2.07/−1.44 to 2.40). Conclusions: There was no clear evidence that high‐frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre‐frontal cortex treatment has a long‐term positive effect on alcohol use or craving as add‐on treatment for alcohol use disorder. High treatment response at 6‐month follow‐up could have limited the possibility to find an effect. [ABSTRACT FROM AUTHOR]

I Satyrium rhodanthum i Schltr. is one of five bird-pollinated members of the genus (Johnson, 1996; Johnson et al., 2011; Johnson & Van der Niet, 2019; Van der Niet et al., 2015). Keywords: motion-activated cameras; Nectariniidae; Orchidaceae; pollinator EN motion-activated cameras Nectariniidae Orchidaceae pollinator 1278 1282 5 11/30/22 20221201 NES 221201 INTRODUCTION Information about the pollination system of plant species is relevant for both basic and applied purposes. Frequency dependence of pollinator visitation rates suggests that pollination niches can allow plant species coexistence. Long-term camera trapping needed to identify sunbird species that pollinate the endangered South African orchid Satyrium rhodanthum. [Extracted from the article]

Objective: Characterize and quantify epithelium in multiple etiologies of laryngotracheal stenosis (LTS) to better understand its role in pathogenesis. Study Design: Controlled in vitro cohort study. Methods: Endoscopic brush biopsy samples of both normal (non‐scar) and scar were obtained in four patients with idiopathic subglottic stenosis (iSGS) and four patients with iatrogenic LTS (iLTS). mRNA expression of basal, ciliary, and secretory cell markers were evaluated using quantitative PCR. Cricotracheal resection tissue samples (n = 5 per group) were also collected, analyzed using quantitative immunohistochemistry, and compared with rapid autopsy tracheal samples. Results: Both iSGS and iLTS‐scar epithelium had reduced epithelial thickness compared with non‐scar control epithelium (P =.0009 and P =.0011, respectively). Basal cell gene and protein expression for cytokeratin 14 was increased in iSGS‐scar epithelium compared with iLTS or controls. Immunohistochemical expression of ciliary tubulin alpha 1, but not gene expression, was reduced in both iSGS and iLTS‐scar epithelium compared with controls (P =.0184 and P =.0125, respectively). Both iSGS and iLTS‐scar had reductions in Mucin 5AC gene expression (P =.0007 and P =.0035, respectively), an epithelial goblet cell marker, with reductions in secretory cells histologically (P <.0001). Conclusions: Compared with non‐scar epithelium, the epithelium within iSGS and iLTS is morphologically abnormal. Although both iSGS and iLTS have reduced epithelial thickness, ciliary cells, and secretory cells, only iSGS had significant increases in pathological basal cell expression. These data suggest that the epithelium in iSGS and iLTS play a common role in the pathogenesis of fibrosis in these two etiologies of laryngotracheal stenosis. Setting: Tertiary referral center (2017–2020). Level of Evidence: NA Laryngoscope, 132:2194–2201, 2022 [ABSTRACT FROM AUTHOR]

The effect of radiation therapy on tumor vasculature has long been a subject of debate. Increased oxygenation and perfusion have been documented during radiation therapy. Conversely, apoptosis of endothelial cells in irradiated tumors has been proposed as a major contributor to tumor control. To examine these contradictions, we use multiphoton microscopy in two murine tumor models: MC38, a highly vascularized, and B16F10, a moderately vascularized model, grown in transgenic mice with tdTomato‐labeled endothelium before and after a single (15 Gy) or fractionated (5 × 3 Gy) dose of radiation. Unexpectedly, even these high doses lead to little structural change of the perfused vasculature. Conversely, non‐perfused vessels and blind ends are substantially impaired after radiation accompanied by apoptosis and reduced proliferation of their endothelium. RNAseq analysis of tumor endothelial cells confirms the modification of gene expression in apoptotic and cell cycle regulation pathways after irradiation. Therefore, we conclude that apoptosis of tumor endothelial cells after radiation does not impair vascular structure. Synopsis: The effects of ionizing radiation on tumor vasculature are disputed. This study shows that radiation of murine tumors using either single (15 Gy) or fractionated (5 × 3 Gy) doses fails to result in significant structural changes of the perfused tumor vasculature. Because apoptosis mainly occurs in non‐perfused vessels and blind ends, the main structural network remains. Perfused and non‐perfused tumor vasculature could be simultaneously imaged using the Ve‐Cadherin‐CreERt2‐tdTomato mouse model resulting in 95% of endothelial cells labeled.Single (15 Gy) and fractionated (5 × 3 Gy) dose of irradiation eliminates smaller, poorly perfused vessels, but the more substantial, perfused vessels remain unchanged, thus not compromising vascular function.Tumor endothelial cell death after irradiation is less prominent in large, perfused vessels than in small non‐perfused vessels.Proliferation of tumor endothelial cells is comprehensively blocked and reduced as early as 12 h after single‐dose IR with longer‐term persistence of cell cycle blockade. [ABSTRACT FROM AUTHOR]

Aims: Compulsivity is a common phenotype among psychiatric disorders, such as obsessive–compulsive disorder (OCD) and gambling disorder (GD). Deficiencies in metacognition, such as the inability to estimate one's performance via confidence judgments could contribute to pathological decision‐making. Earlier research has shown that patients with OCD exhibit underconfidence, while patients with GD exhibit overconfidence. Moreover, it is known that motivational states (e.g. monetary incentives) influence metacognition, with gain (respectively loss) prospects increasing (respectively decreasing) confidence. Here, we reasoned that OCD and GD symptoms might correspond to an exacerbation of this interaction between metacognition and motivation. Methods: We hypothesized GD's overconfidence to be exaggerated during gain prospects, while OCD's underconfidence to be worsened in loss context, which we expected to see represented in ventromedial prefrontal cortex (VMPFC) blood‐oxygen‐level‐dependent activity. We tested those hypotheses in a task‐based functional magnetic resonance imaging (fMRI) design (27 patients with GD, 28 patients with OCD, 55 controls). The trial is registered in the Dutch Trial Register (NL6171). Results: We showed increased confidence for patients with GD versus patients with OCD, which could partly be explained by sex and IQ. Although our primary analyses did not support the hypothesized interaction between incentives and groups, exploratory analyses did show increased confidence in patients with GD specifically in gain context. fMRI analyses confirmed a central role for VMPFC in the processing of confidence and incentives, but no differences between the groups. Conclusion: Patients with OCD and those with GD reside at opposite ends of the confidence spectrum, while no interaction with incentives was found, nor group differences in neuronal processing of confidence. [ABSTRACT FROM AUTHOR]

Objectives: To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses. Methods: We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures. Results: Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies. Conclusions: In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases. Key points: What's already known about this topic? Genome‐wide sequencing for unspecific heterogeneous syndromic and non‐syndromic congenital conditions increases the diagnostic yield compared with standard genetic testing in both the pre‐ and postnatal settings. The diagnostic yield prenatally varies depending on selection criteria and number of anomalies present. What does this study add? Trio exome sequencing should be considered for fetuses with normal cytogenetic and micro‐array analysis and two or more organ defects, fetal hydrops or fetal akinesia syndromes. Selection of cases for exome sequencing should be based on expert prenatal imaging. [ABSTRACT FROM AUTHOR]

Objective: To describe technical aspects and surgical outcomes of endoscopic resection and mucosal reconstitution with epidermal grafting (ie, the Maddern procedure) in the treatment of idiopathic subglottic stenosis. Study Design: Medical record abstraction. Setting: Johns Hopkins Hospital. Methods: Retrospective series of 9 adults with idiopathic subglottic stenosis who underwent the Maddern procedure by a single surgeon over a 5-year period. Prespecified outcomes included (1) perioperative outcomes (Clavien-Dindo grade 4/5 complications, need for staged tracheostomy, hospital length of stay), (2) postoperative outcomes (peak expiratory flow rate [PEFR], need for subsequent airway surgery, tracheostomy at follow-up), and (3) patient-reported quality-of-life outcomes (Clinical COPD Questionnaire, Voice Handicap Index–10, Eating Assessment Tool–10, and 12-Item Short Form Version 2). Wilcoxon matched-pairs signed rank test and Kaplan-Meier analysis were performed. Results: There were no Clavien-Dindo grade 4/5 complications; 2 patients required unplanned staged tracheostomy; and the median length of stay was 3 days. Following endoscopic resection and stent removal, a median of 2 laser resurfacing procedures were required. Two patients developed recurrent stenosis requiring cricotracheal resection (CTR). There were significant improvements in PEFR, Clinical COPD Questionnaire, and Voice Handicap Index–10, without significant difference in Eating Assessment Tool–10. The 12-Item Short Form Version 2 approximated the population norm. Kaplan-Meier analysis demonstrated significant improvement in time to surgery after the final laser resurfacing. Conclusion: The Maddern procedure has a low complication rate and offers durable physiologic improvement in PEFR, limiting need for additional procedures. Risks included need for CTR salvage, temporary tracheostomy, phlegm accumulation, and laryngospasm. It is a surgical option for patients with short dilation intervals who prefer to avoid the risks of CTR. [ABSTRACT FROM AUTHOR]

Background: Eating disorder (ED) symptoms are prevalent in the general population, but their shared genetic underpinnings with psychiatric, metabolic, and anthropometric traits are not known. Here, we examined if polygenic scores (PGSs) of traits associated with anorexia nervosa are also associated with adolescent ED symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: A total of 8654 participants with genotype data and at least one phenotypic measure were included from the ALSPAC study. We associated PGS from 25 traits (16 psychiatric, 4 metabolic, and 5 anthropometric) with eight ED symptoms, including behaviours such as fasting for weight loss and cognitions such as body dissatisfaction. Results: Higher attention deficit hyperactivity disorder PGS and lower educational attainment PGS were associated with fasting for weight loss. Higher insomnia PGS was associated with increased body dissatisfaction. We found no evidence of an association between metabolic trait PGS and any ED symptom. Fat‐free mass, fat mass, and body fat percentage PGSs, were positively associated with binge eating, excessive exercise, fasting for weight loss, body dissatisfaction, and weight and shape concern. Conclusions: ED symptoms are genetically associated with psychiatric and anthropometric, but not with metabolic traits. Our findings provide insights for future genetic research investigating on why some individuals with ED symptoms progress to develop threshold EDs while others do not. Highlights: Several eating disorder symptoms (i.e., binge eating, fasting for weight loss, and body dissatisfaction) in this study were significantly associated with both psychiatric and anthropometric polygenic scores emphasising the genetic complexity of these traits.Eating disorder symptoms as present in the general population and threshold eating disorders may be partially etiologically related (i.e., psychiatric and anthropometric origins), but metabolic genetic factors may differentiate between symptoms and threshold eating disorders.Metabolic disturbances could therefore be the catalyst that puts some individuals on a developmental trajectory leading to threshold eating disorders. [ABSTRACT FROM AUTHOR]

Objective: Iatrogenic laryngotracheal stenosis (iLTS) is the pathologic narrowing of the glottis, subglottis, and/or trachea secondary to intubation or tracheostomy related injury. Patients with type 2 diabetes mellitus (T2DM) are more likely to develop iLTS. To date, the metabolomics and phenotypic expression of cell markers in fibroblasts derived from patients with T2DM and iLTS are largely unknown. Study Design: Controlled in vitro cohort study. Setting: Tertiary referral center (2017-2020). Methods: This in vitro study assessed samples from 6 patients with iLTS who underwent surgery at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea and compared with controls obtained from the trachea of rapid autopsy specimens. Patients with iLTS were subcategorized into those with and without T2DM. Metabolic substrates were identified by mass spectrometry, and cell protein expression was measured by flow cytometry. Results: T2DM iLTS-scar fibroblasts had a metabolically distinct profile and clustered tightly on a Pearson correlation heat map as compared with non-T2DM iLTS-scar fibroblasts. Levels of itaconate were elevated in T2DM iLTS-scar fibroblasts. Flow cytometry demonstrated that T2DM iLTS-scar fibroblasts were associated with higher CD90 expression (Thy-1; mean, 95%) when compared with non-T2DM iLTS-scar (mean, 83.6%; P =.0109) or normal tracheal fibroblasts (mean, 81.1%; P =.0042). Conclusions: Scar-derived fibroblasts from patients with T2DM and iLTS have a metabolically distinct profile. These fibroblasts are characterized by an increase in itaconate, a metabolite related to immune-induced scar remodeling, and can be identified by elevated expression of CD90 (Thy-1) in vitro. [ABSTRACT FROM AUTHOR]

Increased risk of allergen sensitization has been proposed as a possible mechanism.4,5 The objective of this study was to estimate the association between prenatal exposure to ASMs and risk of allergen sensitization in early childhood. Acid suppressant medications, allergy, asthma, bronchiolitis, environmental allergy, food allergy, prenatal exposures We limited analyses to those with complete exposure and outcome data ( I n i = 594 for analyses of any allergen sensitization and aeroallergen sensitization, I n i = 598 for analyses of food allergen sensitization). Keywords: Acid suppressant medications; allergy; asthma; bronchiolitis; environmental allergy; food allergy; prenatal exposures EN Acid suppressant medications allergy asthma bronchiolitis environmental allergy food allergy prenatal exposures 1 4 4 03/29/22 20220301 NES 220301 CONFLICT OF INTEREST The authors have no conflicts of interest. [Extracted from the article]

Objectives: To assess platelet function, buccal mucosal bleeding time and plasma von Willebrand factor concentration in dogs with chronic inflammatory and/or fibrotic liver disease and to compare results with those obtained in healthy dogs. Materials and Methods: Preliminary study including 18 dogs with chronic inflammatory and/or fibrotic liver disease undergoing liver biopsy and 18 healthy age‐matched control dogs. Platelet function was assessed by measuring closure time with the PFA‐100® analyser using adenosine diphosphate (ADP) as an agonist. Buccal mucosal bleeding time, closure time and plasma von Willebrand factor antigen were measured in dogs in both groups. After undergoing ultrasound‐guided needle biopsy, dogs were monitored for haemorrhage to determine if there was an association of any measurement with post‐biopsy bleeding. Results: The closure time was not different between the liver disease group (median 76.3; range 53 to 118.5 seconds) and control group (72.8; 57 to 89.5 seconds). The buccal mucosal bleeding time was longer in the liver disease group (median 138; range 95 to 229 seconds) than the control group (103; 63 to 200 seconds). The plasma von Willebrand factor antigen concentration was not different between the liver disease group (median 203; range 109 to 351%) and control group (165.5; 63 to 246%). Clinical Significance: In this study, dogs with chronic necroinflammatory and/or fibrotic liver disease did not have overt, clinically relevant derangements in platelet function as assessed by buccal mucosal bleeding time, closure time and von Willebrand factor analysis. In addition, none of the dogs undergoing percutaneous ultrasound‐guided biopsy in the study exhibited bleeding complications post‐biopsy procedure. [ABSTRACT FROM AUTHOR]

Non‐native plant pests and pathogens are increasing exponentially, causing extirpation of foundation species. The impact of large‐scale declines in a single host on associated biodiversity is widely documented. However, the impact of multiple host loss on biodiversity and whether these impacts are multiplicative has not been assessed. Ecological theory suggests that systems with greater functional redundancy (alternative hosts) will be more resilient to the loss of sympatric hosts. We test this theory and show its importance in relation to pest/pathogen impact assessments.We assessed the potential impact on biodiversity of the loss of two widely occurring sympatric European tree species, Fraxinus excelsior and Quercus petraea/robur, both of which are currently threatened by a range of pests and pathogens.At the UK scale, the total number of associated species at risk of extirpation from plant diseases affecting these two sympatric hosts is greater than the sum of the associated species at risk from declines in either host alone. F. excelsior hosts 45 obligate species (species only found on that host) and Q. petraea/robur hosts 326. However, a decline in both these trees would impact 512 associated species, across multiple taxon groups, a 38% increase. Assessments at a local scale, 24 mixed F. excelsior–Q. petraea/robur woodlands revealed that these impacts may be even greater due to a lack of functional redundancy. Only 21% of sites were able to provide functional redundancy for F. excelsior and Q. petraea/robur associated species which can use other tree species. In most woodlands, the tree species required to provide functional redundancy were not present, although the site conditions were often suitable for them to grow.Synthesis. Understanding of functional redundancy should be applied to assessments of pests/pathogens impact on biodiversity. In risk assessments, higher impact scores should be given to pests/pathogens affecting hosts occurring with other host plant species already impacted by pests/pathogens. Current pest/pathogen risk assessment approaches that ignore the cumulative, cascading effects shown in this study may allow an insidious, mostly overlooked, driver of biodiversity loss to continue. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto‐cerebellar and meso‐cortico‐limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large‐scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case–control differences and to compare brain‐correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta‐analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age‐ and sex‐matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case–control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co‐variates. After correcting for multiple comparisons, AUD case–control meta‐analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta‐analysis of CUD case–control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross‐disorder comparison of brain correlates of substance use disorders and showed alcohol‐related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex. [ABSTRACT FROM AUTHOR]

Objective: To describe laryngeal findings and voice quality in patients with suspected lung cancer, relative to voice quality and possible laryngeal pathology. Study Design: Prospective cohort study. Setting: Tertiary care center. Methods: Patients with known or suspected lung cancer were approached before planned thoracic surgery, and they completed acoustic analysis, the Voice-Related Quality of Life (V-RQOL) questionnaire, and stroboscopy. The prevalence of dysphonia, V-RQOL and Cepstral Spectral Index of Dysphonia (CSID) scores, and laryngeal findings were examined and compared between patients ultimately found to have lung cancer and those without cancer. Results: Sixty-one patients (45 cancer, 16 noncancer) were analyzed. Patients with cancer were older than those without (mean ± SD, 72.3 ± 9.94 vs 62.6 ± 9.30 years; P =.001). Otherwise, the distribution of stroboscopy findings, acoustic measures, and self-reported voice handicap were similar between the cancer and noncancer cohorts. Prior to surgery, no patients had vocal cord paralysis or obvious neoplasm, though 4 (6.56%) had leukoplakia and 28 (45.9%) had vocal fold movement asymmetry on stroboscopy. Overall, 21 patients (35.0%) had average CSID scores >19, and 13 (21.7%) had CSID scores >24; however, only 4 self-described their voice as not working as it should, and only 2 had a V-RQOL score <85. Conclusion: Patients with suspected lung cancer have moderate dysphonia on acoustic measures, though self-reported impact on quality of life is low. While leukoplakia was seen in 4 patients, obvious neoplasm and occult paralysis were not seen in this cohort. Together, these findings suggest that patients with suspected lung cancer should be assessed for subjective voice dysfunction, but routine laryngeal screening may otherwise be unnecessary. [ABSTRACT FROM AUTHOR]

Across East Africa, mobile phones and tablets are increasingly sitting in the hands of community health workers, clinicians, managers and patients. They are being used for a widening range of functions from diagnostics to health insurance to treatment advice, generating hopes for new healthcare futures and establishing the region as an emerging hub of experimentation in digital health. Drawing on our on‐going ethnographic and anthropological research in Kenya and Tanzania, this article explores the dynamic, varied, experimental, and increasingly financialised terrain of formal digital health projects. While innovation in digital health is a growing feature of healthcare across the globe, in East Africa it is entering into a region already long characterised by NGOised, fragmented and vertical healthcare systems and heavy dependence on foreign capital. This presents challenges to efforts, including the WHO's Universal Health Coverage agenda, to foster national and equitable public healthcare systems. In exploring these issues, we recognise the power, and often deleterious effects, of financial capital that foregrounds markets in global digital health, but we also open space for a (still critical) recognition of East African‐led digital and data technology movements. We believe more research is needed to understand the often painstakingly slow and politically charged work in which governments seek to connect digital health technologies to what already exists while coordinating the work of stakeholders. While innovation remains crucial, what is perhaps needed, then, is for it to be joined by more talk of coordination, regulation, interoperability and standards. [ABSTRACT FROM AUTHOR]

Objective: Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment. Study Design: Controlled ex vivo cohort study. Setting: Tertiary care center. Methods: mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin. Results: There was greater infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, FoxP3+CD4+ Tregs, and FoxP3+CD8+ early effector T cells in the submucosa of iLTS specimens as compared with controls (P <.05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4+ cells and "other" cells. Conclusion: This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4+ cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS. [ABSTRACT FROM AUTHOR]

Objectives: Laryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis, targeted by paradigm‐shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD‐1/PD‐L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored. Study Design: Controlled ex vivo study. Methods: Expression of PD‐1, PD‐L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGFβ1) and analyzed for PD‐L1 expression by quantitative real‐time polymerase chain reaction (n = 6). Results: iLTS specimens exhibited increased expression of PD‐1, PD‐L1, and CD4 (all P <.0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD‐1 and CD4 (P <.0167) compared to controls. PD‐1, PD‐L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD‐L1 (the cognate ligand for PD‐1). Conclusion: Expression of both PD‐1 and its ligand PD‐L1 are significantly greater in patients with iLTS compared to controls, and PD‐1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD‐1/PD‐L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD‐1/PD‐L1 axis for the treatment of LTS. Level of Evidence: N/A Laryngoscope, 131:967–974, 2021 [ABSTRACT FROM AUTHOR]

Objective: Genome‐wide association studies have identified multiple genomic regions associated with anorexia nervosa. No genome‐wide studies of other eating disorders, such as bulimia nervosa and binge‐eating disorder, have been performed, despite their substantial heritability. Exploratively, we aimed to identify traits that are genetically associated with binge‐type eating disorders. Method: We calculated genome‐wide polygenic scores for 269 trait and disease outcomes using PRSice v2.2 and their association with anorexia nervosa, bulimia nervosa, and binge‐eating disorder in up to 640 cases and 17,050 controls from the UK Biobank. Significant associations were tested for replication in the Avon Longitudinal Study of Parents and Children (up to 217 cases and 3,018 controls). Results: Individuals with binge‐type eating disorders had higher polygenic scores than controls for other psychiatric disorders, including depression, schizophrenia, and attention deficit hyperactivity disorder, and higher polygenic scores for body mass index. Discussion: Our findings replicate some of the known comorbidities of eating disorders on a genomic level and motivate a deeper investigation of shared and unique genomic factors across the three primary eating disorders. [ABSTRACT FROM AUTHOR]

Questions: Can bark characteristics be used to determine the suitability of trees to host epiphytic bryophytes and lichens or are other tree and site characteristics more important? Identification of substitute hosts is required in the face of epidemic tree deaths due to diseases that are a threat to affiliated epiphytic communities. We assess the suitability of seven phorophytes to host the epiphytes associated with the UK native oak species, Quercus petraea and Quercus robur, which are currently threatened by a range of pests and pathogens. Location: Six botanic gardens and arboreta across the UK. Method: We recorded the site, habitat, tree (height, diameter at breast height [1.3 m; DBH], percentage canopy cover) and bark characteristics (pH, conductivity, density, water-holding capacity, hardness, topography) and epiphytic community composition on Acer pseudoplatanus, Castanea sativa, Fagus sylvatica, Fraxinus excelsior, Quercus cerris, Quercus petraea, Quercus robur, Quercus rubra and Tilia × europaea. In total 230 trees were surveyed across the six sites. Results: Comparisons between all trees showed significant correlations between similarities in community composition and bark characteristics. However, "tree characteristics" (species, height, DBH and canopy over) explained more of the variation in epiphytic community composition than bark and site characteristics. Phorophytes with similar epiphytic community richness or composition to native oaks did not necessarily have similar bark characteristics. Non-native oaks and the non-native hybrid Tilia × europaea supported similar epiphyte communities to the native oaks and are suggested as substitute phorophytes. Conclusion: Using bark traits is not a reliable method to assess the suitability of substitute phorophytes to conserve epiphytic communities. Instead, the epiphytes hosted by a wider range of phorophytes should be recorded to allow an assessment of their suitability as substitute hosts and hence aid management decisions on replacement phorophytes following tree loss. [ABSTRACT FROM AUTHOR]

Increased fire activity due to climate change may impact the successional dynamics of boreal forests, with important consequences for caribou habitat. Early successional forests have been shown to support lower quantities of caribou forage lichens, but geographic variation in, and controls on, the rates of lichen recovery has been largely unexplored. In this study, we sampled across a broad region in northwestern Canada to compare lichen biomass accumulation in ecoprovinces, including the Saskatchewan Boreal Shield, the Northwest Territories Taiga Shield, and Northwest Territories Taiga Plains, divided into North and South. We focused on the most valuable Cladonia species for boreal and barren‐ground caribou: Cladonia mitis and C. arbuscula, C. rangiferina and C. stygia, and C. stellaris and C. uncialis. We developed new allometric equations to estimate lichen biomass from field measurements of lichen cover and height; allometries were consistent among ecoprovinces, suggesting generalizability. We then used estimates of lichen biomass to quantify patterns of lichen recovery in different stand types, ecoprovinces, and with time following stand‐replacing fire. We used a hurdle model to account both for the heterogeneous nature of lichen presence (zero inflation) and for the range of abundance in stands where lichen was present. The first component of the hurdle model, a generalized linear model, identified stand age, stand type, and ecoprovince as significant predictors of lichen presence. With a logistic growth model, a measure of lichen recovery (time to 50% asymptotic value) varied from 28 to 73 yr, dependent on stand type and ecoprovince. The combined predictions of the hurdle model suggest the most rapid recovery of lichen biomass across our study region occurred in jack pine in the Boreal Shield (30 yr), while stands located in the Taiga Plains (North and South) required a longer recovery period (approximately 75 yr). These results provide a basis for estimating future caribou habitat that encompasses some of the large variation in fire effects on lichen abundance and vegetation types across the range of boreal and barren‐ground caribou in North America. [ABSTRACT FROM AUTHOR]

Most individuals with obesity or overweight have difficulty maintaining weight loss. The weight-reduced state induces changes in many physiological processes that appear to drive weight regain. Here, we review the use of cell biology, genetics, and imaging techniques that are being used to begin understanding why weight regain is the normal response to dieting. As with obesity itself, weight regain has both genetic and environmental drivers. Genetic drivers for "thinness" and "obesity" largely overlap, but there is evidence for specific genetic loci that are different for each of these weight states. There is only limited information regarding the genetics of weight regain. Currently, most genetic loci related to weight point to the central nervous system as the organ responsible for determining the weight set point. Neuroimaging tools have proved useful in studying the contribution of the central nervous system to the weight-reduced state in humans. Neuroimaging technologies fall into three broad categories: functional, connectivity, and structural neuroimaging. Connectivity and structural imaging techniques offer unique opportunities for testing mechanistic hypotheses about changes in brain function or tissue structure in the weight-reduced state. [ABSTRACT FROM AUTHOR]

The most widely reported threat to boreal and mountain populations of woodland caribou (Rangifer tarandus caribou; caribou) involves habitat‐ or disturbance‐mediated apparent competition (DMAC). With DMAC, natural and anthropogenic disturbances that increase the abundance of deciduous‐browsing cervids (e.g., moose [Alces alces], deer [Odocoileus spp.]) are thought to promote predator (especially wolf [Canis lupus]) numbers, which heightens predation risk to caribou. We know most about the effects of DMAC on caribou where the species is under threat by anthropogenic activities in relatively productive southern boreal and mountain systems. Yet, >60% of extant boreal caribou range in North America consists of northern shield and taiga ecoregions of low productivity where caribou may compete with only 1 ungulate species (moose) in the context of DMAC. In this environment, we know very little of how DMAC acts as a limiting factor to caribou. In Saskatchewan, Canada, from 2014–2018, using a combination of vegetation sampling, aerial surveys, and telemetry data (n = 38 wolves), we searched for evidence of DMAC (trends in data consistent with the hypothesis) in an 87,193‐km2 section of the Western Boreal Shield, a poorly productive but pristine region (0.18% of land cover classed as an anthropogenic feature) with a historically high fire‐return interval (47% of stands aged <40 years). Despite the high levels of disturbance, moose density was relatively low (47 moose/1,000 km2), likely because of the scarcity of deciduous or mixed‐wood stands and low abundance of deciduous browse in the young conifer stands that dominated the landscape. In contrast, boreal caribou density was relatively high for the species (37 caribou/1,000 km2). Wolf density (3.1 wolves/1,000 km2) and pack sizes (x¯ = 4.0 wolves/pack) were low and resident (established) territories were large (x¯ = 4,360 km2; 100% minimum convex polygon). The low density of wolves mirrored the low (standardized) ungulate biomass index (UBI; moose + boreal caribou) of the study area (0.36 UBI/km2). We conclude that wolf and hence caribou populations were not responding in accordance with the outcomes generally predicted by DMAC in our study area because the requisite strong, positive response to fire of deciduous‐browse and alternate‐prey abundance was lacking. As a limiting factor to caribou, DMAC is likely modulated at a macroecological scale by factors such as net primary productivity, a corollary to the general hypothesis that we advance here (i.e., primary productivity hypothesis of DMAC). We caution against managing for caribou based on the presumption of DMAC where the mechanism does not apply, which may include much of boreal caribou range in the north. © 2020 The Wildlife Society. At present, our management approach to boreal caribou throughout their Canada‐wide range is predicated on the assumption that disturbance‐mediated apparent competition is an important consideration for all boreal caribou populations. The supposition that large‐scale wildfire disturbance, resulting in younger forests, can generate the habitat conditions necessary to affect increased abundance of alternate prey, in turn increasing wolf populations and limiting caribou population growth, is inconsistent with what we observed in the Saskatchewan Boreal Shield. Instead, we observed low densities of wolves and low densities of moose despite high natural disturbance in our study area. [ABSTRACT FROM AUTHOR]

Studies of microbiome variation in wildlife often emphasize host physiology and diet as proximate selective pressures acting on host‐associated microbiota. In contrast, microbial dispersal and ecological drift are more rarely considered. Using amplicon sequencing, we characterized the bacterial microbiome of adult female (n = 86) Sable Island horses (Nova Scotia, Canada) as part of a detailed individual‐based study of this feral population. Using data on sampling date, horse location, age, parental status, and local habitat variables, we contrasted the ability of spatiotemporal, life history, and environmental factors to explain microbiome diversity among Sable Island horses. We extended inferences made from these analyses with both phylogeny‐informed and phylogeny‐independent null modelling approaches to identify deviations from stochastic expectations. Phylogeny‐informed diversity measures were correlated with spatial and local habitat variables, but null modelling results suggested that heterogeneity in ecological drift, rather than differential selective pressures acting on the microbiome, was responsible for these correlations. Conversely, phylogeny‐independent diversity measures were best explained by host spatial and social structure, suggesting that taxonomic composition of the microbiome was shaped most strongly by bacterial dispersal. Parental status was important but correlated with measures of β‐dispersion rather than β‐diversity (mares without foals had lower alpha diversity and more variable microbiomes than mares with foals). Our results suggest that between host microbiome variation within the Sable Island horse population is driven more strongly by bacterial dispersal and ecological drift than by differential selective pressures. These results emphasize the need to consider alternative ecological processes in the study of microbiomes. [ABSTRACT FROM AUTHOR]

Summary: Soil carbon (C) pools and plant community composition are regulated by nitrogen (N) and phosphorus (P) availability. Atmospheric N deposition impacts ecosystem C storage, but the direction of response varies between systems. Phosphorus limitation may constrain C storage response to N, hence P application to increase plant productivity and thus C sequestration has been suggested.We revisited a 23‐yr‐old field experiment where N and P had been applied to upland heath, a widespread habitat supporting large soil C stocks. At 10 yr after the last nutrient application we quantified long‐term changes in vegetation composition and in soil and vegetation C and P stocks.Nitrogen addition, particularly when combined with P, strongly influenced vegetation composition, favouring grasses over Calluna vulgaris, and led to a reduction in vegetation C stocks. However, soil C stocks did not respond to nutrient treatments. We found 40% of the added P had accumulated in the soil.This study showed persistent effects of N and N + P on vegetation composition, whereas effects of P alone were small and showed recovery. We found no indication that P application could mitigate the effects of N on vegetation or increase C sequestration in this system. [ABSTRACT FROM AUTHOR]

Tree planting is increasingly being proposed as a strategy to combat climate change through carbon (C) sequestration in tree biomass. However, total ecosystem C storage that includes soil organic C (SOC) must be considered to determine whether planting trees for climate change mitigation results in increased C storage. We show that planting two native tree species (Betula pubescens and Pinus sylvestris), of widespread Eurasian distribution, onto heather (Calluna vulgaris) moorland with podzolic and peaty podzolic soils in Scotland, did not lead to an increase in net ecosystem C stock 12 or 39 years after planting. Plots with trees had greater soil respiration and lower SOC in organic soil horizons than heather control plots. The decline in SOC cancelled out the increment in C stocks in tree biomass on decadal timescales. At all four experimental sites sampled, there was no net gain in ecosystem C stocks 12–39 years after afforestation—indeed we found a net ecosystem C loss in one of four sites with deciduous B. pubescens stands; no net gain in ecosystem C at three sites planted with B. pubescens; and no net gain at additional stands of P. sylvestris. We hypothesize that altered mycorrhizal communities and autotrophic C inputs have led to positive 'priming' of soil organic matter, resulting in SOC loss, constraining the benefits of tree planting for ecosystem C sequestration. The results are of direct relevance to current policies, which promote tree planting on the assumption that this will increase net ecosystem C storage and contribute to climate change mitigation. Ecosystem‐level biogeochemistry and C fluxes must be better quantified and understood before we can be assured that large‐scale tree planting in regions with considerable pre‐existing SOC stocks will have the intended policy and climate change mitigation outcomes. [ABSTRACT FROM AUTHOR]

The latency associated with bone metastasis emergence in castrate‐resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single‐cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor‐intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor‐intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor‐intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long‐term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor‐intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone‐metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune‐based therapies in solid cancers. Synopsis: Tumor‐intrinsic type I IFN is lost upon outgrowth of dormant prostate cancer cells in bone, driving metastasis. Therapeutic reversal of tumor‐intrinsic IFN loss enhances tumor cell visibility and the effectiveness of systemic immunomodulatory agents against bone‐metastasis. Tumor‐intrinsic type I IFN and associated immune signaling is lost in prostate cancer cells that have spread to bone.Tumor‐intrinsic type I IFN status is linked to the outgrowth of dormant prostate cancer cells in bone.Therapeutic restoration of tumor‐intrinsic type I IFN inflates immunogenicity and immunotherapeutic response. [ABSTRACT FROM AUTHOR]

1. Diel rhythms of foraging activity by animal flower visitors can reflect niche partitioning and are considered an important component of selection on floral traits. However, it has been notoriously difficult to obtain objective information on the patterns of flower visitation by crepuscular and nocturnal insects. 2. Motion‐activated cameras were used for field‐based studies of hawkmoth foraging behaviour on six African plant species. 3. The results showed that short‐tongued hawkmoth species forage mainly around dusk and then sporadically throughout the night, whereas long‐tongued hawkmoth species feed consistently throughout the night, with a peak shortly before midnight. 4. These results provide the first quantitative estimates of diel patterns of interactions between multiple hawkmoth and plant species and, when combined with qualitative reports from other studies, suggest that differences in diel activity between the two main hawkmoth functional groups (short‐ and long‐tongued) are consistent across the Old and New Worlds. [ABSTRACT FROM AUTHOR]

Introduction: Causes of small-fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor-3 (FGFR-3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS-HDS) in cryptogenic SFN.Methods: One hundred fifty-five patients with biopsy-proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS-HDS and IgG vs FGFR-3.Results: Forty-eight percent of SFN patients had serum antibodies, 37% with IgM vs TS-HDS and 15% with IgG vs FGFR-3. TS-HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non-length-dependent nerve pathology. Nintey-two percent of patients with acute-onset SFN had serum IgM vs TS-HDS.Discussion: Autoantibodies directed against TS-HDS and FGFR-3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS-HDS may be a marker for SFN with an acute onset. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To describe patients with delayed diagnosis of human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC) after initial incorrect diagnosis of branchial cleft cyst or nondiagnostic workup of unilateral neck mass.Study Design: Retrospective case series.Methods: Patients with delayed diagnosis of HPV-OPC after initial nondiagnostic workup for unilateral neck mass were eligible. Medical record abstraction was performed to describe clinical characteristics at initial presentation and later diagnosis of HPV-OPC. To estimate nodal growth rates, the short axis diameter of the lymph nodes was determined from imaging reports.Results: Six patients met eligibility criteria. After a median interval of 42 months (range, 3 months-7 years) from initial presentation with unilateral neck mass, patients were diagnosed with HPV-OPC. At the time of HPV-OPC diagnosis, five were AJCC eighth edition overall stage I, and one was stage II. Primary tumors were T0 or T1 in the majority (83.3%, n = 5). Among five patients with available serial imaging, despite diagnostic delay, three of five still had a single lymph node without involvement of additional nodes, whereas the remaining two developed additional suspicious nodes (ipsilateral and contralateral). Two of five developed evidence of extranodal extension. Median lymph node growth was 9.5% per year (range, -6% to 32%).Conclusions: Although the natural history of HPV-OPC is not well understood, this case series suggests that it can be slow growing and mimic benign processes, leading to diagnostic delays. Adults presenting with neck masses should undergo complete diagnostic evaluation.Level Of Evidence: 4 Laryngoscope, 130:392-397, 2020. [ABSTRACT FROM AUTHOR]

Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general. [ABSTRACT FROM AUTHOR]