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Herein, we present a tool called Evident that can be used for deriving effect sizes for a broad spectrum of metadata variables, such as mode of birth, antibiotics, socioeconomics, etc., to provide power calculations for a new study. Evident can be used to mine existing databases of large microbiome studies (such as the American Gut Project, FINRISK, and TEDDY) to analyze the effect sizes for planning future microbiome studies via power analysis. For each metavariable, the Evident software is flexible to compute effect sizes for many commonly used measures of microbiome analyses, including α diversity, β diversity, and log-ratio analysis. In this work, we describe why effect size and power analysis are necessary for computational microbiome analysis and show how Evident can help researchers perform these procedures. Additionally, we describe how Evident is easy for researchers to use and provide an example of efficient analyses using a dataset of thousands of samples and dozens of metadata categories.

IntroductionSingle-stage revision arthroplasty for periprosthetic joint infection (PJI) may yield comparable infection-free survivorship with two-stage revision arthroplasty. It is unclear if the most common mode of failure of single-stage revision arthroplasty is infection or aseptic loosening. In this meta-analysis, we sought to (1) determine survivorship and (2) compare rates of different etiologies of failure of single-stage revision total hip arthroplasty (THA) and total knee arthroplasty (TKA).MethodsPreferred Reporting Items for Systematic Review and Meta-analyses guidelines search was done using search terms for "single stage revision," "exchange arthroplasty," "periprosthetic infection," "PJI," and "single stage." Patient demographics such as age, body mass index, and mean follow-up time were recorded. Overall survivorship and rates of revision surgery were aggregated using a random-effects model. Comparison of septic and aseptic loosening rates was done by risk difference and associated 95% confidence interval (CI) calculation.ResultsTwenty-four studies were identified with 2,062 and 147 single-stage revision THA and TKA procedures performed between 1984 and 2019, respectively. The weighted mean follow-up and age were 69.8 months and 66.3 years, respectively, with 55% men overall. The all-cause revision surgery rate was 11.1% and 11.8% for THA and TKA, respectively. The revision surgery rate secondary to infection and aseptic loosening and associated 95% CI for the risk difference for THA and TKA was 5.5% and 3.3% (-1.7% to 5.0%), and 3% and 8.8% (-11.4% to 2.3%), respectively. Revision surgeries due to instability and fracture combined and mortality rate were both less than 3%.DiscussionSingle-stage revision THA and TKA for PJI demonstrated overall high rates of survivorship, low mortality, and revision surgeries secondary to infection and aseptic loosening to be equivalent. Aseptic loosening after single-stage revision TKA might be higher than in primary TKA. As implant survivorship from infection improves in PJI, surgeons should be aware of aseptic loosening as an equally common mode of failure.

INTRODUCTION: Controversy exists on the ideal type of fixation in total knee arthroplasty (TKA). Noncemented fixation has been theorized to improve patient outcomes and longevity of implantation without increased risk of aseptic loosening or radiolucent lines. We sought to compare (1) patient-reported outcomes, (2) survivorship, and (3) revision rates for all-cause and aseptic loosening in a noncemented tantalum total knee with its cemented counterpart. METHODS: Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were searched using a combination of keywords trabecular metal, tantalum knee, total knee arthroplasty, and cementless trabecular. Patient demographics such as age, sex, and body mass index were collected. Outcomes such as Knee Society Scores (KSSs), revisions, and radiolucent lines were recorded for analysis. RESULTS: Four randomized controlled trials involving 507 patients with an average 5-year follow-up were eligible for meta-analysis. No differences were observed in any demographics such as age, sex, body mass index, nor preoperative KSS. Patients in the cemented cohort improved from preoperative KSS 46.4 to postoperative KSS 90.4 while the tantalum cohort improved from 46.4 to 89.3. No statistical difference was observed in postoperative KSS mean difference between groups. Six patients from the tantalum group underwent revision with one patient for aseptic loosening. Twelve patients from the cemented group underwent revision with four patients for aseptic loosening. No statistical difference was observed between rates of revision, aseptic loosening, or radiolucent line development. DISCUSSION: Patient-reported outcomes improved postoperatively in both groups. No differences were detected between the cemented and noncemented TKAs in patient-reported outcomes, revision rates, or radiolucent line development. Noncemented tantalum fixation seems equivalent to cemented TKA survivorship. Longer term follow-up of these randomized controlled trials may provide a clearer understanding whether a difference exists.

Abstract Distinct pathways and molecules may support embryonic versus postnatal thymic epithelial cell (TEC) development and maintenance. Here, we identify a mechanism by which TEC numbers and function are maintained postnatally. A viable missense allele (C120Y) of Ovol2, expressed ubiquitously or specifically in TECs, results in lymphopenia, in which T cell development is compromised by loss of medullary TECs and dysfunction of cortical TECs. We show that the epithelial identity of TECs is aberrantly subverted towards a mesenchymal state in OVOL2-deficient mice. We demonstrate that OVOL2 inhibits the epigenetic regulatory BRAF-HDAC complex, specifically disrupting RCOR1-LSD1 interaction. This causes inhibition of LSD1-mediated H3K4me2 demethylation, resulting in chromatin accessibility and transcriptional activation of epithelial genes. Thus, OVOL2 controls the epigenetic landscape of TECs to enforce TEC identity. The identification of a non-redundant postnatal mechanism for TEC maintenance offers an entry point to understanding thymic involution, which normally begins in early adulthood.

Abstract Treatment-resistant depression (TRD) is a severe form of major depressive disorder (MDD) with substantial public health impact and poor treatment outcome. Treatment outcome in MDD is significantly heritable, but genome-wide association studies have failed to identify replicable common marker alleles, suggesting a potential role for uncommon variants. Here we investigated the hypothesis that uncommon, putatively functional genetic variants are associated with TRD. Whole-exome sequencing data was obtained from 182 TRD cases and 2021 psychiatrically healthy controls. After quality control, the remaining 149 TRD cases and 1976 controls were analyzed with tests designed to detect excess burdens of uncommon variants. At the gene level, 5 genes, ZNF248, PRKRA, PYHIN1, SLC7A8, and STK19 each carried exome-wide significant excess burdens of variants in TRD cases (q

Abstract Background The oral cavity is the gateway to the bacteria community in the lung. Disruption of the symbiotic balance of the oral microbiota has been associated with respiratory diseases. However, little is known about the relationship between oral bacteria and respiratory outcomes in the general population. We aimed to describe the associations between oral bacteria, lung function, and lung inflammation in a community-based population. Methods Oral (gingival) samples were collected concurrently with spirometry tests in 477 adults (47% males, median age 28 years) from the RHINESSA study in Bergen, Norway. Bacterial DNA from the 16S rRNA gene from gingival fluid were sequenced by Illumina®MiSeq. Lung function was measured using spirometry and measurement of fractional exhaled nitric oxide (FeNO) were performed to examine airway inflammation. Differential abundance analysis was performed using ANCOM-BC, adjusting for weight, education, and smoking. Results The abundance of the genera Clostridiales , Achromobacter, Moraxella, Flavitalea and Helicobacter were significantly different among those with low FEV1 (

Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free α- [hCGα] and β-subunits [hCGβ]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCGα was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCGα, hCGβ, and hCG-h in relation to TH regulation and child brain function.

Approximately 5.7% of blunt traumas involve cervical spine (C-spine) injuries. While spine fractures are often stable and treated non-operatively, lack of access to spine specialty care results in transfer to tertiary care facilities, placing substantial financial burden on both hospitals and patients. Thus, identifying patient and injury characteristics associated with operative treatment of C-spine fractures may help reduce over-triage.

BackgroundMen who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984-1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]).ResultsWe found that family Succinivibrionaceae, S24-7, Mogibacteriaceae, Coriobacteriaceae, and Erysipelotrichaceae were significantly higher (p

BACKGROUND:Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. RESULTS:PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (> 80th percentile) vs. "low" (

ABSTRACT The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent due, in part, to variation in sample sizes and ethnicity. Thus, an association between the vaginal microbiota and preterm labor continues to be debated. Yet, before assessing associations between the composition of the vaginal microbiota and preterm labor, a robust and in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required. Here, we report a large longitudinal study (n = 474 women, 1,862 vaginal samples) of a predominantly African-American cohort—a population that experiences a relatively high rate of pregnancy complications—evaluating associations between individual identity, gestational age, and other maternal characteristics with the composition of the vaginal microbiota throughout gestation resulting in term delivery. The principal factors influencing the composition of the vaginal microbiota in pregnancy are individual identity and gestational age at sampling. Other factors are maternal age, parity, obesity, and self-reported Cannabis use. The general pattern across gestation is for the vaginal microbiota to remain or transition to a state of Lactobacillus dominance. This pattern can be modified by maternal parity and obesity. Regardless, network analyses reveal dynamic associations among specific bacterial taxa within the vaginal ecosystem, which shift throughout the course of pregnancy. This study provides a robust foundational understanding of the vaginal microbiota in pregnancy and sets the stage for further investigation of this microbiota in obstetrical disease. IMPORTANCE There is debate regarding links between the vaginal microbiota and pregnancy complications, especially spontaneous preterm birth. Inconsistencies in results among studies are likely due to differences in sample sizes and cohort ethnicity. Ethnicity is a complicating factor because, although all bacterial taxa commonly inhabiting the vagina are present among all ethnicities, the frequencies of these taxa vary among ethnicities. Therefore, an in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required prior to evaluating associations between the vaginal microbiota and obstetrical disease. This initial investigation is a large longitudinal study of the vaginal microbiota throughout gestation resulting in a term delivery in a predominantly African-American cohort, a population that experiences disproportionally negative maternal-fetal health outcomes. It establishes the magnitude of associations between maternal characteristics, such as age, parity, body mass index, and self-reported Cannabis use, on the vaginal microbiota in pregnancy.

Protocols to differentiate human pluripotent stem cells have advanced in terms of cell type specificity and tissue-level complexity over the past 2 decades, which has facilitated human disease modeling in the most relevant cell types. The ability to generate induced PSCs (iPSCs) from patients further enables the study of disease mutations in an appropriate cellular context to reveal the mechanisms that underlie disease etiology and progression. As iPSC-derived disease models have improved in robustness and scale, they have also been adopted more widely for use in drug screens to discover new therapies and therapeutic targets. Advancement in genome editing technologies, in particular the discovery of CRISPR-Cas9, has further allowed for rapid development of iPSCs containing disease-causing mutations. CRISPR-Cas9 technologies have now evolved beyond creating single gene edits, aided by the fusion of inhibitory (CRISPRi) or activation (CRISPRa) domains to a catalytically dead Cas9 protein, enabling inhibition or activation of endogenous gene loci. These tools have been used in CRISPR knockout, CRISPRi, or CRISPRa screens to identify genetic modifiers that synergize or antagonize with disease mutations in a systematic and unbiased manner, resulting in identification of disease mechanisms and discovery of new therapeutic targets to accelerate drug discovery research. However, many technical challenges remain when applying large-scale functional genomics approaches to differentiated PSC populations. Here we review current technologies in the field of iPSC disease modeling and CRISPR-based functional genomics screens and practical considerations for implementation across a range of modalities, applications, and disease areas, as well as explore CRISPR screens that have been performed in iPSC models to-date and the insights and therapies these screens have produced.

Here, the authors present Sparse Estimation of Correlations among Microbiomes (SECOM), a tool devised to characterize both linear and nonlinear relationships in microbiome data. When applied to human skin and infant gut microbiome data, SECOM is able to retrieve taxa interactions undescribed by previous methods.

Urbanization requires human comfort that leads to industrial growth that alters existing physical and atmospheric conditions and pollutes the environment. This study area covers 200 km2 located in the northeast of the Greater Visakhapatnam Municipal Corporation (GVMC). The study area is famous for industries as well as tourism due to its bowl-shape topography and rich wild flora and fauna. Study was carried out using Landsat-8 and Landsat-9 satellite data for the years 2018, 2021, and 2022 to assess land surface temperature (LST) and the impact of air pollutants to identify human health hotspots. Industrial and vehicular emissions release harmful gases such as CO2, CO, oxides of nitrogen, sulphur, and suspended particulate matter (SPM) into the atmosphere. The LST for 2018 and 2021 results are nearly the same while the LST for 2022 decreased relatively by 3°C. Data from the monitoring stations located at the Police Barracks, Gnanapuram, and Visakhapatnam Port-Trust show that the ambient air quality with its corresponding LST in the industrial area has been identified with high LST with a 0.67°C increase from 2018 to 2021. There is a decrease of nearly 2°C from 2021 to 2022 at the monitoring stations of the Police Barracks and Gnanapuram located in urban areas, whereas Visakhapatnam Port-Trust is located in the vicinity of industries. The poor Air Quality Index (AQI) is creating discomfort and reduction of visibility in the vicinity. The relative humidity for 2018 is 72%, for 2021 is 64%, and for 2022 is 76%, which causes feelings of stickiness and sweat, and in rare cases skin irritation was reported. The regression analysis of AQI with LST shows a negative correlation in April 2018 and a positive correlation in March 2021 and April 2022. This indicates that the prominent parameter PM10 in AQI contains both cooling and warming properties. Practical Applications: The study was carried out on land surface temperature (LST) and the influence of air pollution and its impact on human health. Practical applications of LST are to identify the urban heat island (UHI) in order to predict micro- to macroclimate zones for urban human comfort and assessment of energy demand, and so on. The impact of air pollutants on LST affects human health. The research focuses on identifying human health hotspots. The LST and air pollutants are the major driving factors. The LST for 2018 and 2021 were comparatively same, while 2022 shows a decrease of LST 3°C. The ambient air quality data when overlaid on the resultant LST shows that Gnanapuram and the Police Barracks areas identified as human health hotspots. The wind speed levels are low, supporting heat retention on the surface. The relative humidity results in feelings of stickiness and sweat and some rare cases of skin irritation. In general, in 2021, the poor Air Quality Index (AQI) was creating discomfort and reduction of visibility in the vicinity. The relative humidity for 2018 was 72%, and for 2021 AQI values were high, thus creating discomfort. The prominent parameter in AQI, PM10, contains both cooling properties of sulphates and the warming nature of black carbon. Therefore, the LST with AQI shows a negative correlation in April 2018 and positive correlation in March 2021 and April 2022. [ABSTRACT FROM AUTHOR]

Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.