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Background It has been shown that metrics recorded for instrument kinematics during robotic surgery can predict urinary continence outcomes. Objective To evaluate the contributions of patient and treatment factors, surgeon efficiency metrics, and surgeon technical skill scores, especially for vesicourethral anastomosis (VUA), to models predicting urinary continence recovery following robot-assisted radical prostatectomy (RARP). Design, setting, and participants Automated performance metrics (APMs; instrument kinematics and system events) and patient data were collected for RARPs performed from July 2016 to December 2017. Robotic Anastomosis Competency Evaluation (RACE) scores during VUA were manually evaluated. Training datasets included: (1) patient factors; (2) summarized APMs (reported over RARP steps); (3) detailed APMs (reported over suturing phases of VUA); and (4) technical skills (RACE). Feature selection was used to compress the dimensionality of the inputs. Outcome measurements and statistical analysis The study outcome was urinary continence recovery, defined as use of 0 or 1 safety pads per day. Two predictive models (Cox proportional hazards [CoxPH] and deep learning survival analysis [DeepSurv]) were used. Results and limitations Of 115 patients undergoing RARP, 89 (77.4%) recovered their urinary continence and the median recovery time was 166 d (interquartile range [IQR] 82–337). VUAs were performed by 23 surgeons. The median RACE score was 28/30 (IQR 27–29). Among the individual datasets, technical skills (RACE) produced the best models (C index: CoxPH 0.695, DeepSurv: 0.708). Among summary APMs, posterior/anterior VUA yielded superior model performance over other RARP steps (C index 0.543–0.592). Among detailed APMs, metrics for needle driving yielded top-performing models (C index 0.614–0.655) over other suturing phases. DeepSurv models consistently outperformed CoxPH; both approaches performed best when provided with all the datasets. Limitations include feature selection, which may have excluded relevant information but prevented overfitting. Conclusions Technical skills and “needle driving” APMs during VUA were most contributory. The best-performing model used synergistic data from all datasets. Patient summary One of the steps in robot-assisted surgical removal of the prostate involves joining the bladder to the urethra. Detailed information on surgeon performance for this step improved the accuracy of predicting recovery of urinary continence among men undergoing this operation for prostate cancer.

Genome‐wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID‐19) cases and outbreaks. We performed whole‐genome sequencing of 27 SARS‐CoV‐2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (

BACKGROUND Currently, weight loss remains the main management strategy for NAFLD, but the weight loss intention and methods remain poorly characterized. METHODS We analysed data about the perception of weight status, intention and methods to lose weight amongst 3,822 persons with NAFLD (United States Fatty Liver Index ≥ 30) from the National Health and Nutrition Examination Survey, 2001-2014. RESULTS Only 53.9% of people with NAFLD intended to lose weight, 91.8% with perception of overweight and 8.2% with normal weight perception. Persons with perception of overweight or overweight/obese status were four times more likely to try to lose weight (adjusted odds ratios 3.9 and 4.2, respectively, both P

BACKGROUND Updated prevalence and outcome data for nonobese NAFLD for the multi-ethnic US population is limited. OBJECTIVES We aimed to investigate the prevalence, clinical characteristics and mortality of obese and nonobese individuals with NAFLD in the United Sates. METHODS A retrospective study was conducted using the 1999-2016 NHANES databases. We determined hazard ratio stratified by obesity status in NAFLD individuals using Cox regression and log-rank test. RESULTS Overall NAFLD prevalence was 32.3%: 22.7% were obese and 9.6% were nonobese, with increasing trend over time for obese NAFLD, but not nonobese NAFLD. Amongst those with NAFLD, 29.7% (95% CI: 27.8%-31.7%) were nonobese, of which 13.6% had lean NAFLD. Nonobese NAFLD was more common in older (40.9% if ≥ 65 vs. 24.2% if

BACKGROUND CONTEXT Spine surgery with posterior approaches may involve extensive manipulation of native structures, resulting in significant postoperative pain. Liposomal bupivacaine (LB) is an injectable analgesic that has demonstrated efficacy in decreasing postoperative pain and opioid requirements in patients across multiple surgical subspecialties. PURPOSE To consolidate and analyze the findings of retrospective cohort-matched studies and prospective randomized controlled trials investigating the use of LB in spine surgery. STUDY DESIGN A systematic review. STUDY SAMPLE Retrospective cohort-matched studies and randomized controlled trials (RCTs) investigating the efficacy of injected LB in spinal surgery compared with a control/no treatment group. METHODS MEDLINE, Cochrane controlled trials register, and Google Scholar were searched to identify all studies that examined the effect of LB use on outcomes in spine surgery. Our search identified 10 articles that independently evaluated the effect of LB on reduction of postoperative opioid use, pain scores, hospital length of stay, cost, and incidence of adverse effects. The principles of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) were applied to assess the quality of evidence from each study. RESULTS Ten studies were analyzed (1,112 total patients). LB was associated with significantly lower millimolar morphine equivalents (MME) of postoperative opioids, especially in opiate-tolerant patients, visual analog scale (VAS) scores, area under the curve (AUC) of cumulative pain scores, numeric pain scale scores, and hospital length of stay (LOS), with comparable or lower odds of adverse effects relative to controls. CONCLUSIONS Low-quality evidence suggests that liposomal bupivacaine may safely decrease postoperative opioid requirements, pain scores, and length of stay in patients undergoing spine surgery, whereas moderate-quality evidence does not support its use at this time. Therefore, additional standardized well-powered prospective studies are necessary to more clearly assess the efficacy of LB in spine surgery.

Background: data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: in this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (0·05 for all analyses). Interpretation: in this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Background Maternal nutrition interventions are inadequately integrated into antenatal care (ANC). Alive & Thrive aimed to strengthen delivery of micronutrient supplements and intensify interpersonal counseling and community mobilization through government ANC services. Objectives We compared nutrition-intensified ANC (I-ANC) with standard ANC (S-ANC) on coverage of nutrition interventions and maternal nutrition practices. Methods We used a cluster-randomized design with cross-sectional baseline (2017) and endline (2019) surveys (n ∼660 pregnant and 1800 recently delivered women per survey) and a repeated-measures longitudinal study in 2018–2019 (n = 400). We derived difference-in-difference effect estimates (DIDs) for diet diversity, consumption of micronutrient supplements, weight monitoring, and early breastfeeding practices. Results Despite substantial secular improvements in service coverage from India's national nutrition program, women in the I-ANC arm received more home visits [DID: 7–14 percentage points (pp)] and counseling on core nutrition messages (DID: 10–23 pp) than in the S-ANC arm. One-third of women got ≥3 home visits and one-fourth received ≥4 ANC check-ups in the I-ANC arm. Improvements were greater in the I-ANC arm than in the S-ANC arm for any receipt and consumption of iron–folic acid (DID: 7.5 pp and 9.5 pp, respectively) and calcium supplements (DID: 14.1 pp and 11.5 pp, respectively). Exclusive breastfeeding improved (DID: 7.5 pp) but early initiation of breastfeeding did not. Maternal food group consumption (∼4 food groups) and probability of adequacy of micronutrients (∼20%) remained low in both arms. Repeated-measures longitudinal analyses showed similar results, with additional impact on consumption of vitamin A–rich foods (10 pp, 11 g/d), other vegetables and fruits (22–29 g/d), and gestational weight gain (0.4 kg). Conclusions Intensifying nutrition in government ANC services improved maternal nutrition practices even with strong secular trends in service coverage. Dietary diversity, supplement consumption, and breastfeeding practices remained suboptimal. Achieving greater behavior changes will require strengthening the delivery and use of maternal nutrition services integrated into ANC services in the health system. This trial was registered at clinicaltrials.gov as NCT03378141.

Shotgun metatranscriptomics (MTX) is an increasingly practical way to survey microbial community gene function and regulation at scale. This review begins by summarizing the motivations for community transcriptomics and the history of the field. We then explore the principles, best practices, and challenges of contemporary MTX workflows: beginning with laboratory methods for isolation and sequencing of community RNA, followed by informatics methods for quantifying RNA features, and finally statistical methods for detecting differential expression in a community context. In thesecond half of the review, we survey important biological findings from the MTX literature, drawing examples from the human microbiome, other (nonhuman) host-associated microbiomes, and the environment. Across these examples, MTX methods prove invaluable for probing microbe–microbe and host–microbe interactions, the dynamics of energy harvest and chemical cycling, and responses to environmental stresses. We conclude with a review of open challenges in the MTX field, including making assays and analyses more robust, accessible, and adaptable to new technologies; deciphering roles for millions of uncharacterized microbial transcripts; and solving applied problems such as biomarker discovery and development of microbial therapeutics.

The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.

Vietnam has successfully reduced population stunting, but ethnic minority groups are being systematically left behind, limiting progress on national reductions. This mixed methods study aims to understand how policy drivers of stunting reduction differ between ethnic majority and minority communities. We used decomposition analysis to explain key determinants of stunting change between 2000 and 2010; and framework analysis to qualitatively assess changes in policy, actors and narratives that have underpinned these over decades. Our analysis shows that stunting reductions are associated with increased household wealth (accounting for 61% of change), improved access to specific health services (16%), and changes in level of maternal education (12%). Despite multiple actors involved in change and a large set of policies designed to address inequities, many among Vietnam’s defined ethnic minority groups are not finding themselves able to effectively engage with central government plans for their communities, and central policies often do not consider their preferences or limitations. This in turn impacts the nutrition of minority groups through the determinants above. Vietnam has achieved the easier portion of stunting reduction through national economic growth and sustained commitment to socially-oriented policy. In order to tackle the remaining pockets of high malnutrition, more attention, thought and funding will need to focus on marginalised ethnic minority communities. The current national development discourse aims to incorporate minorities into mainstream majority systems. This paper argues that policy should rather take into account their particular needs and preferences to address and overcome the identified determinants of malnutrition.

Since April 19, 2021, all persons aged ≥16 years in the United States have been eligible to receive a COVID-19 vaccine. As of May 30, 2021, approximately one half of U.S. adults were fully vaccinated, with the lowest coverage and lowest reported intent to get vaccinated among young adults aged 18-39 years (1-4). To examine attitudes toward COVID-19 vaccination and vaccination intent among adults in this age group, CDC conducted nationally representative household panel surveys during March-May 2021. Among respondents aged 18-39 years, 34.0% reported having received a COVID-19 vaccine. A total of 51.8% were already vaccinated or definitely planned to get vaccinated, 23.2% reported that they probably were going to get vaccinated or were unsure about getting vaccinated, and 24.9% reported that they probably or definitely would not get vaccinated. Adults aged 18-24 years were least likely to report having received a COVID-19 vaccine and were most likely to report being unsure about getting vaccinated or that they were probably going to get vaccinated. Adults aged 18-39 years with lower incomes, with lower educational attainment, without health insurance, who were non-Hispanic Black, and who lived outside of metropolitan areas had the lowest reported vaccination coverage and intent to get vaccinated. Concerns about vaccine safety and effectiveness were the primary reported reasons for not getting vaccinated. Vaccination intent and acceptance among adults aged 18-39 years might be increased by improving confidence in vaccine safety and efficacy while emphasizing that vaccines are critical to prevent the spread of COVID-19 to friends and family and for resuming social activities (5).

Background: The impact of negative pressure wound therapy (NPWT) as an adjunct to colorectal surgery is largely unknown. The purpose of this study was to determine whether NPWT impacts wound compli...

Objectives To examine data from Delaware nursing homes to determine prevalence of age-related eye diseases (AREDs), vision impairment, and blindness and to compare the findings with the results of 11 US investigations of vision and eye health in nursing homes. Design This is a cross-sectional, retrospective study of nursing home patients. Setting and Participants Twenty nursing homes in Delaware participated in the study, yielding comprehensive eye examination records for 2019 study participants. Methods Summary statistics and regression analyses. Results The overall prevalence of vision impairment or blindness was 63.8% and was above 60% for each age, sex, and race category. Prevalence of vision impairment or blindness was 68.4% among patients with cataracts, 69.4% among patients with macular degeneration, 70.5% among patients with glaucoma, and 68.4% among patients with diabetic retinopathy. Prevalence of blindness was 14.1%. Among patients with AREDs, prevalence of blindness ranged from 15.0% for patients with cataracts to 22.6% for patients with diabetic retinopathy. When compared with other investigations, we found wide variation in vision and eye factors reported and wide variation in the prevalence of those factors. Only 4 studies diagnosed both AREDs and visual function. Seven studies reported AREDs, and 7 reported vision impairment and/or blindness. Vision impairment or blindness ranged from 29% to 67%; cataract ranged from 32% to 83%; macular degeneration ranged from 4.6% to 70.7%. Glaucoma ranged from 5.3% to 41.4%; diabetic retinopathy ranged from 1.7% to 3.1%. Conclusions and Implications Comprehensive eye examinations showed that vision impairment and blindness affected 63.8% of nursing home residents. Compared with other studies, there was a wide range of vision factors reported and wide variation in the prevalence of vision impairment or blindness and AREDs. This investigation suggests the importance of eye care in nursing homes and the importance of reporting standard vision and eye health factors to inform policy and practice.

BackgroundChronic obstructive pulmonary disease (COPD) and asthma rank among the leading causes of respiratory morbidity, particularly in low- and middle-income countries. This qualitative study aimed to explore the healthcare pathways of patients with chronic respiratory disease, and factors influencing their ability to access healthcare in Vietnam, where COPD and asthma are prevalent.MethodsWe conducted 41 in-depth interviews among patients, including 31 people with COPD, eight with asthma and two with asthma-COPD overlap syndrome. Participants were recruited at provincial- or national-level health facilities in two urban and two rural provinces in Vietnam. The interviews were audio-recorded, transcribed, and analysed using thematic analysis.ResultsPatients’ healthcare pathways were complex and involved visits to multiple health facilities before finally obtaining a definitive diagnosis at a provincial- or national-level hospital. Access to healthcare was affected considerably by participants’ limited knowledge of their respiratory conditions, the availability of social support, especially from family members, the costs of healthcare as well as health system factors (including the coverage of public health insurance, the distance to health facilities, and attitude of healthcare providers).ConclusionThe study demonstrated the need for improved access to timely diagnosis and treatment of chronic lung disease within the lower level of the health system. This can be achieved by enhancing the communication skills and diagnostic capacity of local healthcare workers. Health education programmes for patients and caregivers will contribute to improved control of lung disease.

Background Millions of children fail to meet their developmental potential and experience mental health concerns globally. Evidence is mixed on whether growth beyond the first 1000 d of life influences intellectual functioning and mental health in school-age children. Objectives We examined associations of childhood growth before and after the first 1000 d of life with child intellectual functioning and mental health at age 6-7 y. Methods We used data from a follow-up of a randomized controlled trial of preconception supplementation (PRECONCEPT study) in Vietnam. A total of 5011 women participated in the study and 1579 children were born during 2012-2014. At age 6-7 y, child intellectual functioning was assessed using the Wechsler Intelligence Scale for Children, and mental health concerns were measured using the Strengths and Difficulties Questionnaire. Multivariable linear models were used to examine the independent association of child size at age 2 y [height-for-age z-score (HAZ) and body-mass-index z-score (BMIZ)] and conditional measures of linear and ponderal growth between the ages of 2 and 7 y. Results HAZ at 2 y was positively associated with the Full-Scale Intelligence Quotient (β = 1.4; 95% CI: 0.5, 2.2 points) and its subdomains, namely Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (β = 1.0-1.4 points). Higher HAZ at 2 y was associated with lower overall mental health concerns (β = -0.24; 95% CI: -0.47, -0.01) and peer problems (β = -0.08; 95% CI: -0.17, -0.01). Faster height gain between 2 and 7 y was associated with higher total intellectual functioning (β = 0.9; 95% CI: 0.02, 1.8) and fewer emotional issues (β = -0.09; 95% CI: -0.18, -0.01). BMIZ at 2 y was not associated with intellectual functioning but was marginally associated with higher conduct and peer problems. Conditional weight gain between 2 and 7 y was not associated with child intellectual functioning or mental health in young school-age children. Conclusions Child linear growth both during and beyond the first 1000 d is positively associated with intellectual functioning and mental health during the early school-age years.

Otitis media (OM), known as a middle ear infection, is the leading cause of antibiotic prescriptions for children. With wide-spread use of antibiotics in OM, resistance to antibiotics continues to decrease the efficacy of the treatment. Furthermore, as the presence of a middle ear biofilm has contributed to this reduced susceptibility to antimicrobials, effective interventions are necessary. A miniaturized 3D-printed microplasma jet array has been developed to inactivate Pseudomonas aeruginosa, a common bacterial strain associated with OM. The experiments demonstrate the disruption of planktonic and biofilm P. aeruginosa by long-lived molecular species generated by microplasma, as well as the synergy of combining microplasma treatment with antibiotic therapy. In addition, a middle ear phantom model was developed with an excised rat eardrum to investigate the antimicrobial effects of microplasma on bacteria located behind the eardrum, as in a patient-relevant setup. These results suggest the potential for microplasma as a new treatment paradigm for OM.

Aims Takotsubo syndrome (TTS) is a form of acute myocardial inflammation, often triggered by catecholamine release surges, which accounts for approximately 10% of ‘myocardial infarctions’ in female patients above the age of 50. Its associated substantial risk of in‐hospital mortality is mainly driven by the development of hypotension and shock. While hypotension is induced largely by factors other than low cardiac output, its precise cause is unknown, and clinical parameters associated with hypotension have not been identified previously. We therefore sought to identify the incidence and clinical/laboratory correlates of early hypotension in TTS. Methods and results We analysed the in‐hospital data of patients recruited to the South Australian TTS Registry. Associations between the development of hypotension, patient demographics, severity of the acute TTS attack, and key biochemical markers were sought. One hundred thirteen out of 319 patients (35%) were hypotensive (median systolic blood pressure 80 mmHg) during their index hospitalization. Development of hypotension preceded all in‐hospital deaths (n = 8). On univariate analyses, patients who developed hypotension had lower left ventricular ejection fraction (P = 0.009), and higher plasma N‐terminal pro brain natriuretic peptide and troponin‐T concentrations (P = 0.046 and 0.008, respectively), all markers of severity of the TTS attack; hypotension also occurred less commonly in male than in female patients (P = 0.014). On multivariate linear regression analysis, female sex and lower left ventricular ejection fraction were independent correlates of the development of hypotension (P = 0.009 and 0.010, respectively). Conclusions Early development of hypotension is very common in TTS, and its presence is associated with a substantial risk of in‐hospital mortality. Hypotension is a marker of severe TTS attacks and occurs more commonly in female TTS patients.

Background The traumatic dislocation of the radial head in children is commonly treated by closed reduction. Sometimes, however, this strategy of treatment may not be effective due to the location of soft tissues in the radio‐shoulder joint. The literature presents a few cases of the irreducible radial head dislocation with ulnar plastic deformation. Because it is a relatively rare condition, such a traumatic dislocation can be easily missed. Neglected injuries can lead to unwanted complications and unpredictable surgical outcomes. Case presentation This study presents a relatively rare case of traumatic radial head dislocation with ulnar plastic deformation in a 3‐year‐old child, which was successfully treated by open reduction. The examined case did not require osteotomy and ligamentous reconstruction. The initial attempt of closed reduction failed due to annular ligament interposition, which has been detected on MRI. After 3 months of treatment, the range of motion of the operated arm gradually improved. At the 6‐month follow‐up, the Mayo elbow‐performance score indicated an excellent treatment outcome. Conclusions The delayed treatment of radial head dislocation with ulnar plastic deformation can hinder the supination and pronation of the forearm, resulting in elbow/forearm deformity. The earlier this condition is detected, the easier it will be to treat it and the better the treatment outcome will be. The examined case of irreversible traumatic dislocation, successfully treated by open reduction, may help to treat radial head dislocation better., Traumatic radial head dislocation with ulnar plastic deformation is very rare. These neglected traumas resulted in a far more complex injury. Here is a rare case of injury in a 3‐year‐old child that was successfully treated. The initial close‐reduction attempt was fail due to annular ligament interposition. Delayed treatment can lead to deformity of elbow and forearm.

National-level climate actions will be vital in achieving global temperature goals in the coming decades. Near-term (2025–2030) plans are laid out in Nationally Determined Contributions; the next step is the submission of long-term strategies for 2050. At present, national scenarios underpinning long-term strategies are poorly coordinated and incompatible across countries, preventing assessment of individual nations’ climate policies. Here we present a systematic and standardized, yet flexible, scenario framework varying 2050 emissions to build long-term national energy and climate mitigation scenarios. Applying the framework to six major Asian countries reveals individual challenges in energy system transformation and investment needs in comparable scenarios. This framework could be a starting point for comprehensive assessments as input to the Global Stocktake over the coming years., 世界各国の2050年の温室効果ガス削減目標を分析するための国際的な研究フレームワークの提案. 京都大学プレスリリース. 2021-05-28., Pathways to global climate targets. 京都大学プレスリリース. 2021-06-01.

Adolescent birth is a major global concern owing to its adverse effects on maternal and child health. We assessed trends in adolescent birth and examined its associations with child undernutrition in Bangladesh using data from seven rounds of Demographic and Health Surveys (1996–2017, n = 12,006 primiparous women with living children, Adolescent birth is a major global concern owing to its adverse effects on maternal and child health. We assessed trends in adolescent birth and examined its associations with child undernutrition in Bangladesh using data from seven rounds of Demographic and Health Surveys. Our analysis demonstrates that birth during adolescence, a common occurrence in Bangladesh, is associated with child undernutrition.

BACKGROUND AND AIMS Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. APPROACH AND RESULTS To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC-driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10-11 ; human FN1, P = 1.5 × 10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P

Automated performance metrics (APMs) objectively measure surgeon performance during a robot-assisted radical prostatectomy (RARP). Machine learning (ML) has shown that APMs, especially during the vesico-urethral anastomosis (VUA) of the RARP, are predictive of long-term outcomes such as continence recovery time. This study focuses on APMs during the VUA, specifically on stitch versus sub-stitch levels, to distinguish surgeon experience. During the VUA, APMs, recorded by a systems data recorder (Intuitive Surgical), were reported for each overall stitch (C(total)) and its individual components: needle handling/targeting (C(1)), needle driving (C(2)), and suture cinching (C(3)) (Figure 1A). These metrics were organized into three datasets (GlobalSet [whole stitch], RowSet [independent sub-stitches], and ColumnSet [associated sub-stitches] (Figure 1B) and applied to three ML models (AdaBoost, Gradient Boosting, and Random Forest) in order to solve two classifications tasks: experts (≥ 100 cases) vs. novices (

We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult Drosophila brains that captures circadian circuit-wide cycling under simulated day/night cycles. Light input analysis confirms that CRYPTOCHROME (CRY) is the primary circadian photoreceptor and mediates clock disruption by constant light (LL), and that eye light input is redundant to CRY; 3-h light phase delays (Friday) followed by 3-h light phase advances (Monday morning) simulate the common practice of staying up later at night on weekends, sleeping in later on weekend days then returning to standard schedule Monday morning [weekend light shift (WLS)]. PER and TIM oscillations are highly synchronous across all major circadian neuronal subgroups in unshifted light schedules for 11 d. In contrast, WLS significantly dampens PER oscillator synchrony and rhythmicity in most circadian neurons during and after exposure. Lateral ventral neuron (LNv) oscillations are the first to desynchronize in WLS and the last to resynchronize in WLS. Surprisingly, the dorsal neuron group-3 (DN3s) increase their within-group synchrony in response to WLS. In vivo, WLS induces transient defects in sleep stability, learning, and memory that temporally coincide with circuit desynchrony. Our findings suggest that WLS schedules disrupt circuit-wide circadian neuronal oscillator synchrony for much of the week, thus leading to observed behavioral defects in sleep, learning, and memory.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out. This Perspective from the Harvard Chan Microbiome in Public Health Center describes a generalizable and scalable approach to stool and oral microbiome and metadata collection in the Micro-N (Microbiome Among Nurses) study, to show how to carry out prospective studies of the microbiome.

Objective Exercise-induced repolarization changes have not been systematically evaluated in children and young adults with congenital heart disease (CHD). We carried out this study to assess the QTc responses during exercise in children and young adults (≤ 21 years) with CHD with comparison to those with structurally normal hearts. Methods Baseline QRS duration, calculated baseline QTc, QTc at 4 min of recovery and delta QTc was measured in 360 exercise stress tests which were performed in 360 subjects (137 stress tests in patients with CHD [CHD group] and 223 stress tests in patients with structurally normal hearts). The effects of presence of CHD and potential confounders on primary outcome measure, change in QTc (delta QTc), and secondary outcome measures (QTc at baseline and QTc at 4 min of recovery) were determined using multiple linear regression analyses. Results The baseline QTc and the QTc at 4 min of recovery in the CHD group was longer than patients with structurally normal hearts (respective p values = .00 and .001). No significant difference was noted in delta QTc between the CHD and structurally normal heart groups. Conclusions While patients with CHD had a longer QRS duration and QTc interval at baseline than those with structurally normal hearts, these differences did not persist or augment with exercise.

Hydroponic production of vegetables is becoming more common, especially in regions with unfavorable climate for year-round crop production. However, if viruses are present in the hydroponics feed water, then there is a chance that infectious viruses will be internalized into the tissues of hydroponically grown vegetables. When this happens, surface sanitization of postharvest vegetables may not be effective because the sanitizer cannot disinfect the internalized viruses. In this study, we determined if the effectiveness of peracetic acid (PAA), a sanitizer used in the vegetable industry, is affected by the location of viruses (produce surface or interior tissue) in microgreen arugula. Either internally or externally contaminated hydroponically grown microgreen arugula was then treated with PAA at either 30 or 80 ppm for up to 3 min. The PAA disinfection efficacy was higher when the RV was on the arugula surface (approximately 5-log10 in PFU after 3 min of exposure), instead of the arugula interior (1.5-log10 in PFU after 3 min of exposure). However, PAA disinfection efficacy of TV was not dependent on the virus location in arugula. For both internalized TV and RV, the disinfection efficacy was less than 2-log10 in PFU using all the tested PAA concentrations and exposure times examined here. Thus, both the type and location of virus in fresh vegetables may influence the virus disinfection of postharvest vegetables. Therefore, the optimization of sanitation for postharvest fresh vegetables is needed to reduce foodborne viral infection risks.

Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2–3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0–2 h and glucose incremental area under the blood glucose curve at 0–2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2–3 h relative to baseline level predicted an increase in hunger at 2–3 h (r = 0.16, P

P wave centric ambulatory electrocardiographic (ECG) monitoring has emerged as an important tool aiding the diagnosis of arrhythmias. However, their efficacy and user experience in infants and young children are not well established. A retrospective study was performed to detail clinical and user experience of ECG monitoring using the Carnation Ambulatory Monitor (CAM) patch (Bardy Diagnostics Inc., Seattle, WA) in patients less than 10 kg. Additionally, 2 different monitor locations (over the sternum and horizontal over the left axilla) were assessed to address the optimal placement in these patients. A total of 33 CAM reports from 25 patients, aged 0 to15 months were included in the study. Mean patient age was 4.2 months ± 5.0 and mean weight was 5.3 kg ± 2.4. Thirty-six percent of patients (9/25) had known congenital heart disease. Indications for monitoring included: tachyarrhythmia (15/33, 45%), bradyarrhythmia (6/33, 18%), ectopic rhythm (9/33, 27%), cardiac tumor (1/33, 1%), and prolonged QT interval (1/33, 1%). All CAM reports showed clear, identifiable P waves which were diagnostic and lead to changes in medical management for 30% of patients (e.g., medication adjustments or discharge from cardiology care). We found the upright placement over the sternum performed better than the horizontal placement over the left axilla for small infants and children less than 10 kg. A P wave centric single-lead ECG monitor is helpful in providing accurate diagnostics tracings in infants and small children aiding in their clinical management.

As of February 8, 2021, 59.3 million doses of vaccines to prevent coronavirus disease 2019 (COVID-19) had been distributed in the United States, and 31.6 million persons had received at least 1 dose of the COVID-19 vaccine (1). However, national polls conducted before vaccine distribution began suggested that many persons were hesitant to receive COVID-19 vaccination (2). To examine perceptions toward COVID-19 vaccine and intentions to be vaccinated, in September and December 2020, CDC conducted household panel surveys among a representative sample of U.S. adults. From September to December, vaccination intent (defined as being absolutely certain or very likely to be vaccinated) increased overall (from 39.4% to 49.1%); the largest increase occurred among adults aged ≥65 years. If defined as being absolutely certain, very likely, or somewhat likely to be vaccinated, vaccination intent increased overall from September (61.9%) to December (68.0%). Vaccination nonintent (defined as not intending to receive a COVID-19 vaccination) decreased among all adults (from 38.1% to 32.1%) and among most sociodemographic groups. Younger adults, women, non-Hispanic Black (Black) persons, adults living in nonmetropolitan areas, and adults with lower educational attainment, with lower income, and without health insurance were most likely to report lack of intent to receive COVID-19 vaccine. Intent to receive COVID-19 vaccine increased among adults aged ≥65 years by 17.1 percentage points (from 49.1% to 66.2%), among essential workers by 8.8 points (from 37.1% to 45.9%), and among adults aged 18-64 years with underlying medical conditions by 5.3 points (from 36.5% to 41.8%). Although confidence in COVID-19 vaccines increased during September-December 2020 in the United States, additional efforts to tailor messages and implement strategies to further increase the public's confidence, overall and within specific subpopulations, are needed. Ensuring high and equitable vaccination coverage across all populations is important to prevent the spread of COVID-19 and mitigate the impact of the pandemic.

BACKGROUND & AIMS The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC. METHODS We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre. RESULTS Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤ .04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P

Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called ‘long COVID’, are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.

Vascular liver disease (VLD) presents special challenges in the diagnosis, surveillance, and treatment of hepatocellular carcinoma (HCC). HCC arising in the setting of vascular liver disease is often thought to be due to elevated hepatic arterial blood flow, rather than progressive fibrosis from chronic inflammation as with other chronic liver conditions such as viral hepatitis, autoimmune, and metabolic liver diseases. Vascular alteration inherent in VLD often impedes HCC non‐invasive diagnosis and loco‐regional treatment that depend on vascular properties found in typical liver environment. Benign and pre‐malignant liver nodules such as focal nodular hyperplasia and hepatocellular adenoma are also more common in certain VLDs, further adding to surveillance and diagnostic challenges. In this synopsis, we aimed to review available literature on the epidemiology, surveillance, diagnosis, and management of HCC in patients with VLD and specifically Budd–Chiari syndrome, congenital porto‐systemic shunts, Fontan‐associated liver disease, hereditary hemorrhagic telangiectasia.

Objectives Osteoporosis is a major global health problem, and optimizing bone health during childhood and adolescence with adequate calcium and vitamin D intake is a recommendation to prevent the disease. School milk programs may be a viable approach to help children and adolescents increase calcium and vitamin D intakes while improving their bone health. Methods A review of the literature was conducted on school milk programs, including examination of details regarding these studies and their participants, and assessments of their effects on bone health in children and adolescents. Results Nearly all studies reviewed showed significant increases in the bone health behaviors and outcomes that were measured, such as bone mineral density, milk consumption, and calcium and vitamin D intake. Conclusions School milk programs can be effective in improving bone health in children and adolescents, and public health policies should be considered to help support and fund effective programs that promote bone health and prevent osteoporosis in population health.

Objectives Resources for care among women are crucial for children’s growth and development. The objectives of this cross-sectional study were to determine if: (1) the factor structure of measures of maternal resources for care was comparable across countries and consistent with the theoretical constructs and (2) the measures showed equivalence across contexts. Methods The study included 4400, 4029 and 2746 women from Bangladesh, Vietnam, and Ethiopia, respectively. The measures of resources for care were maternal education, knowledge, height, body mass index, mental well-being, financial autonomy, decision-making, employment, support in chores, and perceived support. Results The factor analysis demonstrated that a two-factor solution best explained the structure of resources for care in all three countries. The first factor was associated with financial autonomy and employment in all three countries and with decision-making in two countries. The second factor was associated with education and knowledge in all three countries. The measures of resources for care had measurement equivalence across countries. Conclusion for Practice Resources for care were structurally similar and measurement equivalent across countries and can be used for measurement in low- and middle-income countries. Additional work examining the structure and cross-context equivalence of resources for care in other settings is warranted.

NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients. The overall NAFLD prevalence was 25.5%, higher in males (p

This study was conducted to determine the prevalence and determinants of medication adherence among patients with HIV/AIDS in southern Vietnam. Methods: A cross-sectional study was conducted in a hospital in southern Vietnam from June to December 2019 on patients who began antiretroviral therapy (ART) for at least 6 months. Using a designed questionnaire, patients were considered adherent if they took correct medicines with right doses, on time and properly with food and beverage and had follow-up visits as scheduled. Multivariable logistic regression was used to identify determinants of adherence. Key findings: A total of 350 patients (from 861 medical records) were eligible for the study. The majority of patients were male (62.9%), and the dominant age group (≥35 years old) accounted for 53.7% of patients. Sexual intercourse was the primary route of transmission of HIV (95.1%). The proportions of participants who took the correct medicine and at a proper dose were 98.3% and 86.3%, respectively. In total, 94.9% of participants took medicine appropriately in combination with food and beverage, and 75.7% of participants were strictly adherent to ART. The factors marital status (odds ratio (OR) = 2.54, 95%CI = 1.51–4.28), being away from home (OR = 1.7, 95%CI = 1.03–2.78), substance abuse (OR = 2.7, 95%CI = 1.44–5.05), general knowledge about ART (OR = 2.75, 95%CI = 1.67–4.53), stopping medication after improvement (OR = 4.16, 95%CI = 2.29–7.56) and self-assessment of therapy adherence (OR = 9.83, 95%CI = 5.44–17.77) were significantly associated with patients’ adherence. Conclusions: Three-quarters of patients were adherent to ART. Researchers should consider these determinants of adherence in developing interventions in further studies.

INTRODUCTION Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch. METHODS ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA

Metabolic constraints in the tumor microenvironment constitute a barrier to effective antitumor immunity and similarities in the metabolic properties of T cells and cancer cells impede the specific therapeutic targeting of metabolism in either population. To identify distinct metabolic vulnerabilities of CD8+ T cells and cancer cells, we developed a high-throughput in vitro pharmacologic screening platform and used it to measure the cell type–specific sensitivities of activated CD8+ T cells and B16 melanoma cells to a wide array of metabolic perturbations during antigen-specific killing of cancer cells by CD8+ T cells. We illustrated the applicability of this screening platform by showing that CD8+ T cells were more sensitive to ferroptosis induction by inhibitors of glutathione peroxidase 4 (GPX4) than B16 and MC38 cancer cells. Overexpression of ferroptosis suppressor protein 1 (FSP1) or cytosolic GPX4 yielded ferroptosis-resistant CD8+ T cells without compromising their function, while genetic deletion of the ferroptosis sensitivity–promoting enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) protected CD8+ T cells from ferroptosis but impaired antitumor CD8+ T-cell responses. Our screen also revealed high T cell–specific vulnerabilities for compounds targeting NAD+ metabolism or autophagy and endoplasmic reticulum (ER) stress pathways. We focused the current screening effort on metabolic agents. However, this in vitro screening platform may also be valuable for rapid testing of other types of compounds to identify regulators of antitumor CD8+ T-cell function and potential therapeutic targets.

Although the existing flu vaccines elicit strong antigen-specific antibody responses, they fail to provide effective, long term protection – partly due to the absence of robust cellular memory immunity. We hypothesized that co-administration of combination adjuvants, mirroring the flu-virus related innate signaling pathways, could elicit strong cellular immunity. Here, we show that the small molecule adjuvant R848 and the RNA adjuvant PUUC, targeting endosomal TLR7s and cytoplasmic RLRs respectively, when delivered together in polymer nanoparticles (NP), elicits a broadened immune responses in mouse bone marrow-derived dendritic cells (mBMDCs) and a synergistic response in both mouse and human plasmacytoid dendritic cells (pDCs). In mBMDCs, NP-R848-PUUC induced both NF-κB and interferon signaling. Interferon responses to co-delivered R848 and PUUC were additive in human peripheral blood mononuclear cells (PBMCs) and synergistic in human FLT3-differentiated mBMDCs and CAL-1 pDCs. Vaccination with NPs loaded with H1N1 Flu antigen, R848, and PUUC increased percentage of CD8+ T-cells in the lungs, percentage of antigen-specific CD4-T-cells in the spleen, and enhanced overall cytokine-secreting T cell percentages upon antigen restimulation. Also, in the spleen, T lymphopenia, especially after in vitro restimulation with dual adjuvants, was observed, indicating highly antigen-reactive T cells. Our results demonstrate that simultaneous engagement of TLR7 and RIG-I pathways using particulate carriers is a potential approach to improve cellular immunity in flu vaccination.

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome. The beneficial effects of a Mediterranean diet on cardiometabolic health are associated with specific changes in the gut microbiome, suggesting a personalized approach towards cardiometabolic disease prevention.

Objectives This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. Background Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. Methods Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. Results Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p Conclusions Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures might be more appropriate for the identification of arterial disease before adulthood.

Background: We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts. Methods: Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31–3.16; Ptrend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06–2.43; Ptrend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08–2.42; Ptrend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25–2.87; Ptrend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34–3.14, Ptrend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk. Conclusions: Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development. Impact: Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.

Purpose: The purpose of this study is to examine the association of steroid use during orthognathic surgery and postoperative outcomes including major complications, 90-day all-cause readmission, and postoperative length of stay. Methods: A retrospective review was implemented utilizing the Pediatric Health Information System (PHIS) database from 2004 to 2014 was undertaken. Steroid exposure was defined as having been billed for the generic drug code for Dexamethasone (154035) at any time for up to 7 days from the surgery date. Unadjusted and adjusted random-intercept logistic regression models were utilized to assess the association between steroid exposure and these outcomes. Results: The sample included 5194 patients, 54% of patients were exposed to steroids, with 20.16 % exposed only on the day of surgery, 27.76% on the day of surgery and after, and 6.22% after the day of surgery. In models adjusting for age, sex, race, procedure, hospital variation and complex chronic conditions, the odds-ratio of steroid exposure was 3.46 (95% CI = 2.96-4.03) for an increased length of stay, 1.05 (95% CI = 0.81-1.37) for major complications and 1.20 (95% CI = 0.95-1.52) for 90-day all-cause readmission. Conclusion: The administration of steroids in patients undergoing orthognathic surgery is significantly associated with increased odds of length of stay. This may be due to a large set of patients receiving steroids during orthognathic procedure are less healthy than those not selected to receive steroids, and thereby require an increased length of stay. The limitations of large, administrative databases do not allow determination of this, but future prospective study is warranted.

Body composition parameters are linked to cardio-metabolic risk. However, high-quality reference values of body composition are scarce, particularly in Asian population. The aim of study was to construct sex- and age-specific normative reference values of body composition for the Vietnamese population. This study was designed as a cross-sectional investigation that involved 2700 women and 1459 men aged between 20 and 90 (average 48, SD 15) who were participants in the population-based Vietnam Osteoporosis Study. Whole-body composition parameters (e.g., fat mass and lean mass) and site-specific (head, arms, trunk, and legs) parameters were measured by dual-energy X-ray absorptiometry (Hologic Horizon). Reference curves for each parameter and anatomical site were constructed using the Generalized Additive Model for Location Scale and Shape modeling technique. Overall, 8% of women and 11% of men were classified as obese (body mass index ≥ 27.5 kg/m2). Most fat mass was deposited at the trunk (~50%), followed by the leg (~33%). Women had ~10% more body fat (relative to body weight) than men. However, whole-body lean mass was higher in men than women, with the average difference being ~13 kg. Moreover, men had more bone mineral content than women (2110 vs. 1600 g). We also provided a comparison of age-related changes in body composition parameters between Vietnamese and US Whites. These data provide gender- and age-specific reference values of body composition parameters for Vietnamese population. These normative values provide health professionals and the public with a resource for interpretation of body composition data.

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor–stromal interactions. Here we have validated this microphysiological system (MPS) platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment responses in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional monolayer culture and 3-dimensional spheroids., VMTs recapitulate in vivo drug responses and also reconstitute the cellular diversity of tumors.

To further reduce the burden of cardiovascular disease (CVD) and expand prevention efforts, the American Heart Association (AHA) introduced in 2010 the concept of Ideal Cardiovascular Health (ICH), which includes 7 metrics (smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose). Limited data exist on the relation between ICH and long-term CVD risk. The Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study cohort was used to examine the relation between ICH and incident major adverse cardiovascular events (MACE: first occurrence of death, myocardial infarction, stroke, acute ischemic syndrome, or coronary revascularization). The 7 factors of the ICH were scored at study entry on a 0 to 2 scale, resulting in possible range of 0 to 14, with higher scores representing "better" health. Cox regression analyses were used to estimate hazard ratios (HR) of MACE, along with 95% confidence intervals. Over a median follow-up of 12 years, the study population (n = 1,863, 67% women, 42% Black race, mean age 59 years [range 45 to 75]) had 218 MACE. In unadjusted analysis, the ICH score (per 1 unit) was associated with an estimated 12% lower risk of MACE (HR [95% Confidence Interval]: 0.88 [0.82, 0.93]). Adjusting for demographics, education, and quality of life, ICH score was associated with a 10% lower risk of MACE (HR 0.90 [0.84, 0.96]). In a community-based sample of adults, the AHA ICH construct, which includes 7 modifiable CVD risk factors, appears to be a valid measure for predicting long-term risk of MACE.

BACKGROUND: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited. METHODS: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013–2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (