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Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease. In this Resource article, the authors integrate genomic, bioinformatic and flow cytometric data from human bone marrow to provide an atlas of hematopoietic progenitor cell states in health and disease.

Little information is available on the prevalence of Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 eating disorders in adolescence, and eating disorders remain unique in the DSM for not systematically including a criterion for clinical significance. This study aimed to provide the first prevalence report of the full suite of DSM-5 eating disorders in adolescence, and to examine the impact of applying a criterion for clinical significance. In total, 5191 (participation rate: 70%) Australian adolescents completed a survey measuring 1-month prevalence of eating disorder symptoms for all criterial, 'other specified' and unspecified eating disorders, as well as health-related quality of life and psychological distress. The point prevalence of any eating disorder was 22.2% (12.8% in boys, 32.9% in girls), and 'other specified' disorders (11.2%) were more common than full criterial disorders (6.2%). Probable bulimia nervosa and binge eating disorder, but not anorexia nervosa (AN), were more likely to be experienced by older adolescents. Most disorders were associated with an increased odds for being at a higher weight. The prevalence of eating disorders was reduced by 40% (to 13.6%) when a criterion for clinical significance was applied. Eating disorders, particularly 'other specified' syndromes, are common in adolescence, and are experienced across age, weight, socioeconomic and migrant status. The merit of adding a criterion for clinical significance to the eating disorders, similar to other DSM-5 disorders, warrants consideration. At the least, screening tools should measure distress and impairment associated with eating disorder symptoms in order to capture adolescents in greatest need for intervention.

We sought to provide the first point prevalence estimates of muscle dysmorphia (MD), a form of body dysmorphic disorder characterized by a preoccupation with perceived insufficient muscularity, in adolescents. Data were taken from a survey of 3618 Australian adolescents (11.172-19.76 years; 49.3% girls). Measures captured demographic characteristics, symptoms of MD and eating disorders, psychological distress and functional impairment. Diagnostic criteria for MD developed by Pope et al. (1997, , 38(6), 548-557) were applied, entailing preoccupation with insufficient muscularity causing significant levels of distress or disability that cannot be better accounted for by an eating disorder. The point prevalence of MD was 2.2% [95% confidence interval (CI) 1.6-3.0%] among boys and 1.4% (95% CI 0.9-2.0%) among girls. Prevalence was not associated with gender ( = 0.031) or socioeconomic status (SES) (partial 0.001), but was marginally associated with older age (partial = 0.001). Boys with MD were more likely than girls with MD to report severe preoccupation with muscularity ( = 0.259) and a weight-lifting regime that interfered with their life ( = 0.286), whereas girls with MD were more likely to report discomfort with body exposure ( = 0.380). While future epidemiological research using diagnostic interviews is needed to verify these estimates, the findings suggest that MD is relatively common from early to late adolescence. Gender differences in MD prevalence may be minimal; however, the symptom profile appears to diverge between boys and girls. These findings provide a platform for future, analytical research designed to inform clinical and public health interventions.

Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20-57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50-100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.

BackgroundCommunity sample data indicate that weight control efforts in young adulthood may have associations with greater increases in body mass index (BMI) over time.ObjectiveTo determine the prospective associations between weight goals and behaviors in young adults and BMI trajectories over 15-year follow-up using a nationally representative sample.DesignLongitudinal cohort data collected from 2001 to 2018 of the National Longitudinal Study of Adolescent to Adult Health.ParticipantsYoung adults aged 18–26 years old at baseline stratified by gender and BMI category.Main MeasuresPredictors: weight goals, any weight loss/maintenance behaviors, dieting, exercise, disordered eating behaviors. Outcomes: BMI at 7- and 15-year follow-up.Key ResultsOf the 12,155 young adults in the sample (54% female, 32% non-White), 33.2% reported a goal to lose weight, 15.7% to gain weight, and 14.6% to maintain weight. In unadjusted models, all groups have higher mean BMI at 7- and 15-year follow-up. In mixed effect models, goals to lose weight in men with BMI < 18.5 (5.94 kg/m2; 95% CI 2.58, 9.30) and goals to maintain weight in men with BMI ≥ 25 (0.44; 95% CI 0.15, 0.72) were associated with greater BMI increase compared to no weight goal. Engaging in disordered eating behaviors was associated with greater BMI increase in men with BMI < 18.5 (5.91; 2.96, 8.86) and women with 18.5 ≤ BMI < 25 (0.40; 0.16, 0.63). Dieting (− 0.24; − 0.41, − 0.06) and exercise (− 0.31; − 0.45, − 0.17) were associated with lower BMI increase in women with 18.5 ≤ BMI < 25. In women with BMI < 18.5, dieting was associated with greater BMI increase (1.35; 0.33, 2.37).ConclusionsWeight control efforts may have variable effects on BMI over time by gender and BMI category. These findings underscore the need to counsel patients on the effectiveness of weight control efforts and long-term weight management.

Purpose Little is known regarding correlates of help-seeking for a body image problem in adolescents with an eating disorder. This study provides the first population-based investigation of help-seeking correlates among adolescents with an eating disorder. Methods Australian adolescents ( N  = 1002, 75.5% female, mean age = 15.14, SD  = 1.40) who met operational diagnostic criteria for an eating disorder completed a survey assessing help-seeking, and potential correlates of help-seeking (sex, age, body mass index, socio-economic status, migrant status, sexuality, eating disorder diagnosis, psychological distress, and quality of life). Results Only 10.1% of participants reported having sought help. Bivariate analyses revealed that increased likelihood of help-seeking was associated with female sex, sexual minority status, being born outside Australia, older age, having a major eating disorder (compared to having an unspecified or other specified feeding or other eating disorder diagnosis), higher psychological distress, and reduced psychological and social functioning. Older age, being born outside of Australia, and having a major eating disorder were significant independent correlates of help-seeking. Conclusions Very few adolescents with an eating disorder seek help for a body image problem. Promoting early, appropriate help-seeking among those who are younger and/or those with less well-known disorders may be particularly important. Level of Evidence Level III, case-control analytic study.

Objective To document whether elements of a structured history and examination predict adverse outcome of acute sore throat.Design Prospective clinical cohort.Setting Primary care.Participants 14 610 adults with acute sore throat (≤2 weeks’ duration).Main outcome measures Common suppurative complications (quinsy or peritonsillar abscess, otitis media, sinusitis, impetigo or cellulitis) and reconsultation with new or unresolving symptoms within one month.Results Complications were assessed reliably (inter-rater κ=0.95). 1.3% (177/13 445) of participants developed complications overall and 14.2% (1889/13 288) reconsulted with new or unresolving symptoms. Independent predictors of complications were severe tonsillar inflammation (documented among 13.0% (1652/12 717); odds ratio 1.92, 95% confidence interval 1.28 to 2.89) and severe earache (5% (667/13 323); 3.02, 1.91 to 4.76), but the model including both variables had modest prognostic utility (bootstrapped area under the receiver operator curve 0.61, 0.57 to 0.65), and 70% of complications (124/177) occurred when neither was present. Clinical prediction rules for bacterial infection (Centor criteria and FeverPAIN) also predicted complications, but predictive values were also poor and most complications occurred with low scores (67% (118/175) scoring ≤2 for Centor; 126/173 (73%) scoring ≤2 for FeverPAIN). Previous medical problems, sex, temperature, and muscle aches were independently but weakly associated with reconsultation with new or unresolving symptoms.Conclusion Important suppurative complications after an episode of acute sore throat in primary care are uncommon. History and examination and scores to predict bacterial infection cannot usefully identify those who will develop complications. Clinicians will need to rely on strategies such as safety netting or delayed prescription in managing the uncertainty and low risk of complications.

Recent studies, partly based on murine models, suggest childhood immunization and vitamin A supplements may confer protection against malaria infection, although strong evidence to support these theories in humans has so far been lacking. We analyzed national survey data from children aged 6–59 months in four sub-Saharan African countries over an 18-month time period, to determine the risk of Plasmodium spp. parasitemia (n=8390) and Plasmodium falciparum HRP-2 (PfHRP-2)-related antigenemia (n=6121) following vitamin A supplementation and standard vaccination. Bacille Calmette Guerin-vaccinated children were more likely to be PfHRP-2 positive (relative risk [RR]=4.06, 95% confidence interval [CI]=2.00–8.28). No association was identified with parasitemia. Measles and polio vaccination were not associated with malaria. Children receiving vitamin A were less likely to present with parasitemia (RR=0.46, 95% CI=0.39–0.54) and antigenemia (RR=0.23, 95% CI=0.17–0.29). Future studies focusing on climate seasonality, placental malaria and HIV are needed to characterize better the association between vitamin A and malaria infection in different settings. More than half of the world's population is at risk of malaria, with an estimated 198 million clinical cases each year. A vaccine that fully prevents it has not yet been discovered. Most cases of malaria occur among children living in sub-Saharan Africa, a region where many receive routine vaccinations designed to prevent other diseases; for example, 75% of children in sub-Saharan Africa receive measles vaccines. Many also receive vitamin A supplements, which have been linked not only to the protection of a child's vision, but also to a lower risk of death and an improved ability to fight off infections. Some researchers have suggested that vitamin A supplements and routine childhood vaccinations for other diseases may also provide some protection against malaria. For example, some studies performed in mice have shown that a commonly used tuberculosis vaccine may eliminate Plasmodium parasites that cause malaria infections. However, this effect depended on several factors, including how the vaccine was administered and whether the vaccination was given before or after the mouse developed malaria. It is less clear whether vaccines or vitamin A have antimalarial effects in humans. To address this, Hollm-Delgado et al. analyzed national survey data collected from thousands of children aged between 6 months and 5 years old who lived in four different countries in sub-Saharan Africa. The surveys contained information about the vaccines and supplements the children received, and whether their blood showed signs of infection with malaria-causing Plasmodium parasites. Hollm-Delgado et al. found that routine vaccinations did not affect the likelihood of malaria parasites being detected in the child's blood. However, children vaccinated against tuberculosis were more likely to have a specific type of protein released when malaria infects the blood. Hollm-Delgado et al. suspect that the tests may actually have inadvertently detected other parasitic infections in the children, such as Schistosoma, producing false-positive results for malaria. In contrast, Hollm-Delgado et al. found that children who received vitamin A supplements were less likely to become infected with malaria. The benefits of the supplements appeared to be affected by several conditions, including the time of year when the children received their supplements or when they were tested for malaria, and whether their mother had malaria when pregnant. Clinical trials are now needed to confirm these results and investigate how effectively vitamin A prevents malaria.

Whilst next generation sequencing can report point mutations in fixed tissue tumour samples reliably, the accurate determination of copy number is more challenging. The conventional Multiplex Ligation-dependent Probe Amplification (MLPA) assay is an effective tool for measurement of gene dosage, but is restricted to around 50 targets due to size resolution of the MLPA probes. By switching from a size-resolved format, to a sequence-resolved format we developed a scalable, high-throughput, quantitative assay. MLPA-seq is capable of detecting deletions, duplications, and amplifications in as little as 5ng of genomic DNA, including from formalin-fixed paraffin-embedded (FFPE) tumour samples. We show that this method can detect BRCA1, BRCA2, ERBB2 and CCNE1 copy number changes in DNA extracted from snap-frozen and FFPE tumour tissue, with 100% sensitivity and >99.5% specificity.