Miracle-dz/UniFAR-FTUs huggingface dataset:
A scoping review of longitudinal airway microbiota studies

ABSTRACT Introduction The role of the microbiota in inflammatory airway diseases is unclear. Antimicrobial therapies have predominantly been guided by culture results. However, molecular sequencing has shown that the airway microbiota is much more complex and accurate modeling requires longitudinal analysis. Areas covered A Preferred Reporting Items for Systematic Reviews and Meta-Analyses scoping review was performed by searching Medline, Scopus, and Web of Science databases for all longitudinal airway microbiota studies that utilized molecular techniques. 38 studies with 1,993 participants were included in this review. Healthy microbial communities were more diverse, individualized and stable over time. Acute infections resulted in changes in the microbiota that were detected earlier and more sensitively by molecular sequencing than culture. Distinct microbiota profiles have been demonstrated in chronic obstructive pulmonary disease patients associated with exacerbation frequency and severity. Expert opinion Longitudinal studies provide essential data on the stability of the microbiota over time and valuable information about the dynamic interactions between host, disease and microbes. We believe that molecular sequencing will be increasingly incorporated into research and clinical practice in the future. These advances can lead to improved diagnosis, enhanced prescribing guidance and reduce unnecessary antibiotic usage.
Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients With Crohn Disease

Supplemental Digital Content is available in the text ABSTRACT Objectives: We investigated the therapeutic drug monitoring of adalimumab (ADL) on clinical remission (CR) and mucosal healing (MH) rates in paediatric patients with Crohn disease (CD). Furthermore, long-term treatment efficacy of ADL in paediatric CD was evaluated through 3-year follow-up. Methods: We conducted a prospective study of 31 patients with CD who received ADL maintenance therapy and underwent endoscopic evaluation of MH and pharmacokinetic analysis. Patients in CR were identified based on Paediatric Crohn Disease Activity Index (PCDAI) scores less than 10. Patients with MH were identified based on Simple Endoscopic Scores for Crohn Disease (SES-CD) of less than 2. Results: At 4 months and 1 year of ADL treatment, 28 and 26 patients, respectively, were under CR; 13 and 17 patients, respectively, achieved MH. The median trough levels (TLs) of ADL were higher in patients in CR (7.6 ± 3.5 μg/mL) than in patients with active disease (5.1 ± 2.2 μg/mL). ADL TLs were significantly higher in patients who achieved MH than in those who did not (14.2 ± 7.6 vs 7.8 ± 5.2 μg/mL). The optimal cut-point for predicting MH at 1 year of ADL treatment was 8.18 μg/mL. During long-term follow-up, ADL TLs were stably maintained over 10 μg/mL; not only CR and MH but also histologic remission was obtained at a high rate. ADL administration maintained a positive effect on growth during the maintenance period. Conclusions: ADL TLs were significantly higher in paediatric patients with CD who achieved CR or MH. ADL treatment showed long-term stable efficacy and positive effects on growth indicators.
Confidence interval estimation for sensitivity and difference between two sensitivities at a given specificity under tree ordering

This article considers a setting in diagnostic studies (or biomarker study) which involves a healthy class and a diseased class and the latter consists of several subclasses. The problem of interest is to evaluate the accuracy of a biomarker (or a diagnostic test) measured on a continuous scale correctly identifying healthy subjects from diseased subjects without requiring specification of an ordering in terms of marker values for subclasses relative to each other within the diseased class. Such setting is quite common in practice and it falls in the framework of tree ordering or umbrella ordering. This article explores several parametric and nonparametric approaches for estimating confidence intervals of sensitivity of single biomarker and difference between sensitivities of two correlated biomarkers under tree ordering at a given specificity. The performances of all the methods are evaluated and compared by a comprehensive simulation study. A published microarray data set is analyzed using the proposed methods.
Willingness to vaccinate against COVID-19 among Bangladeshi adults: Understanding the strategies to optimize vaccination coverage

Background Although the approved COVID-19 vaccine has been shown to be safe and effective, mass vaccination in Bangladeshi people remains a challenge. As a vaccination effort, the study provided an empirical evidence on willingness to vaccinate by sociodemographic, clinical and regional differences in Bangladeshi adults. Methods This cross-sectional analysis from a household survey of 3646 adults aged 18 years or older was conducted in 8 districts of Bangladesh, from December 12, 2020, to January 7, 2021. Multinomial regression examined the impact of socio-demographic, clinical and healthcare-releated factors on hesitancy and reluctance of vaccination for COVID-19. Results Of the 3646 respondents (2212 men [60.7%]; mean [sd] age, 37.4 [13.9] years), 74.6% reported their willingness to vaccinate against COVID-19 when a safe and effective vaccine is available without a fee, while 8.5% were reluctant to vaccinate. With a minimum fee, 46.5% of the respondents showed intent to vaccinate. Among the respondents, 16.8% reported adequate adherence to health safety regulations, and 35.5% reported high confidence in the country’s healthcare system. The COVID-19 vaccine refusal was significantly high in elderly, rural, semi-urban, and slum communities, farmers, day-laborers, homemakers, low-educated group, and those who had low confidence in the country’s healthcare system. Also, the prevalence of vaccine hesitancy was high in the elderly population, low-educated group, day-laborers, people with chronic diseases, and people with low confidence in the country’s healthcare system. Conclusion A high prevalence of vaccine refusal and hesitancy was observed in rural people and slum dwellers in Bangladesh. The rural community and slum dwellers had a low literacy level, low adherence to health safety regulations and low confidence in healthcare system. The ongoing app-based registration for vaccination increased hesitancy and reluctancy in low-educated group. For rural, semi-urban, and slum people, outreach centers for vaccination can be established to ensure the vaccine’s nearby availability and limit associated travel costs. In rural areas, community health workers, valued community-leaders, and non-governmental organizations can be utilized to motivate and educate people for vaccination against COVID-19. Further, emphasis should be given to the elderly and diseased people with tailored health messages and assurance from healthcare professionals. The media may play a responsible role with the vaccine education program and eliminate the social stigma about the vaccination. Finally, vaccination should be continued without a fee and thus Bangladesh’s COVID vaccination program can become a model for other low and middle-income countries.
Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7‐related osteopetrosis

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three‐step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte‐like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage‐specific gene and surface marker expression proved mesodermal priming, the presence of monocyte‐like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)‐derived osteoclasts hiPSC‐derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC‐osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002‐A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl−/H+‐exchanger ClC‐7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC‐7 displayed residual expression and retained lysosomal co‐localization with OSTM1, the gene coding for the osteopetrosis‐associated transmembrane protein 1, but only ClC‐7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC‐derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss‐of‐function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC‐osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast‐related diseases. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study

Background Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure. Methods and findings Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery. We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m2. Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks’ gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19+5 weeks’ gestation, a change of −0·6 (95% CI −0.8 to −0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks’ gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study’s main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements. Conclusions Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.
Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell-derived endothelial cells from Friedreich's ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency-dependent senescence drove vessel inflammation, remodeling, and PH, while pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.
Effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block

Abstract Background: Dexamethasone has been widely used in brachial plexus block to enhance the effects of brachial plexus block. However, the clinical findings are not consistent with the dosage of dexamethasone prolonging local anesthetic nerve block. Therefore, the purpose of this study was to explore the effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block through network meta-analysis. Methods: We searched PubMed, Web of Science, Cochrane Library, and Embase databases to collect all randomized controlled trials (RCTs) of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block until March 2021. Two researchers then independently screened articles, extracted data, and evaluated the quality of selected literatures. All data was processed by Stata 14.0 and WinBUGS 1.4. 3.software. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: Our study is expected to provide high-quality evidence-based medicine advice for the effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block. Ethics and dissemination: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/PZ5WR.
The roles of conduit redundancy and connectivity in xylem hydraulic functions.

1. Wood anatomical traits shape a xylem segment's hydraulic efficiency and embolism spread resistance due to declining water potential. It has been known for decades that variations in conduit connectivity play a role in altering xylem hydraulics. However, evaluating the precise effect of conduit connectivity has been elusive. The objective is to establish an analytical linkage between conduit connectivity and grouping and tissue-scale hydraulics. 2. It is hypothesized that an increase in conduit connectivity brings improved resistance to embolism spread due to increased hydraulic pathway redundancy. However, an increase in conduit connectivity could also reduce resistance due to increased embolism spread speed with respect to pressure. We elaborate on this trade-off using graph theory, percolation theory, and computational modeling of xylem. The results are validated using anatomical measurements of Acer branch xylem. 3. Considering only species with vessels, increases in connectivity improve resistance to embolism spread without negatively affecting hydraulic conductivity. The often measured grouping index fails to capture the totality of the effect of conduit connectivity on xylem hydraulics. 4. Variations in xylem network characteristics, such as conduit connectivity, might explain why hypothesized trends among woody species, like the 'safety-efficiency' trade-off hypothesis, are weaker than expected.
Is the photometric method using acetone extracts to determine chlorophyll concentrations applicable to Mg‐deficient plants?

A conventional photometric method to determine chlorophyll concentrations in maize leaves was evaluated. It was tested whether in Mg-deficient plant tissue the addition of MgCO3 during pigment extraction converts protoporphyrin IX into chlorophyll, falsifying concentration measurements. The non-destructive N-tester was used as a reference for the destructive chlorophyll determination. It is shown that both methods are valid for the determination of chlorophyll concentration in Mg-deficient leaves.
How are people with mild cognitive impairment or subjective memory complaints managed in primary care? A systematic review

Abstract Background Primary care is typically the first point of contact in the health care system for people raising concerns about their memory. However, there is still a lack of high-quality evidence and understanding about how primary care professionals (PCPs) currently manage people at higher risk of developing dementia. Objectives To systematically review management strategies provided by PCPs to reduce cognitive decline in people with mild cognitive impairment and subjective memory complaints. Method A systematic search for studies was conducted in December 2019 across five databases (EMBASE, Medline, PsycInfo, CINAHL and Web of Science). Methodological quality of included studies was independently assessed by two authors using the Mixed Methods Appraisal Tool. Results An initial 11 719 were found, 7250 were screened and 9 studies were included in the review. Most studies were self-reported behaviour surveys. For non-pharmacological strategies, the most frequent advice PCPs provided was to increase physical activity, cognitive stimulation, diet and social stimulation. For pharmacological strategies, PCPs would most frequently not prescribe any treatment. If PCPs did prescribe, the most frequent prescriptions targeted vascular risk factors to reduce the risk of further cognitive decline. Conclusion PCPs reported that they are much more likely to provide non-pharmacological strategies than pharmacological strategies in line with guidelines on preventing the onset of dementia. However, the quality of evidence within the included studies is low and relies on subjective self-reported behaviours. Observational research is needed to provide an accurate reflection of how people with memory problems are managed in primary care.
Cyamella (a popliteal sesamoid bone) prevalence: A systematic review, meta‐analysis, and proposed classification system

The cyamella is a rare, generally asymptomatic, knee sesamoid bone located in the proximal tendon of the popliteal muscle. Only two studies have investigated cyamella presence/absence in humans, putting ossified prevalence rates at 0.57%–1.8%. We aim to (a) determine cyamella prevalence in a Korean population, (b) examine coincident development of the cyamella and fabella, and (c) perform a systematic review and meta‐analysis on the cyamella in humans. Medical computed tomography scans of 106 individuals were reviewed. A systematic review and meta‐analysis were performed following PRISMA guidelines. Cyamellae were found in 3/212 knees (1.4%), and presence/absence was uncorrelated to height, age, and sex. The cyamella was not found coincidentally with the fabella, although the statistical power was low. Our systematic review/meta‐analysis revealed cyamellae were generally asymptomatic and ossification could occur at 14 years. Cyamellae were equally likely to be found in both sexes, knees, one or both knees, and there appeared to be no global variation in prevalence rates. Cyamellae were found in three distinct locations. There is little support for the role of intrinsic genetic and/or environmental factors in cyamella development in humans. However, the apparent phylogenetic signal in Primates suggests genetics plays a role in cyamella development. We propose a cyamella classification system based on cyamella location (Class I, popliteal sulcus; Class II, tibial condyle; Class III, fibular head) and hypothesize locations may correspond to distinct developmental pathways, and cyamella function may vary with location.
Anatomy-aided deep learning for medical image segmentation: a review

Deep learning (DL) has become widely used for medical image segmentation in recent years. However, despite these advances, there are still problems for which DL-based segmentation fails. Recently, some DL approaches had a breakthrough by using anatomical information which is the crucial cue for manual segmentation. In this paper, we provide a review of anatomy-aided DL for medical image segmentation which covers systematically summarized anatomical information categories and corresponding representation methods. We address known and potentially solvable challenges in anatomy-aided DL and present a categorized methodology overview on using anatomical information with DL from over 70 papers. Finally, we discuss the strengths and limitations of the current anatomy-aided DL approaches and suggest potential future work.