Metagenomic analysis examines oral microbiome changes and interplay with immune response following prenatal total oral rehabilitation.

BACKGROUND: Suboptimal maternal oral health during pregnancy is potentially associated with adverse birth outcomes and increased dental caries risks in children. This study aimed to assess the oral microbiome and immune response following an innovative clinical regimen, Prenatal Total Oral Rehabilitation (PTOR), that fully restores women's oral health to a "disease-free status" before delivery. METHODS: This prospective cohort study assessed 15 pregnant women at baseline and 3 follow-up visits (1 week, 2 weeks, and 2 months) after receiving PTOR. The salivary and supragingival plaque microbiomes were analyzed using metagenomic sequencing. Multiplexed Luminex cytokine assays were performed to examine immune response following PTOR. The association between salivary immune markers and oral microbiome was further examined. RESULTS: PTOR was associated with a reduction of periodontal pathogens in plaque, for instance, a lower relative abundance of Tannerella forsythia and Treponema denticola at 2 weeks compared to the baseline (p < 0.05). The alpha diversity of plaque microbial community was significantly reduced at the 1-week follow-up (p < 0.05). Furthermore, we observed significant changes in the Actinomyces defective-associated carbohydrate degradation pathway and Streptococcus Gordonii-associated fatty acid biosynthesis pathway. Two immune markers related to adverse birth outcomes significantly differed between baseline and follow-up. ITAC, negatively correlated with preeclampsia severity, significantly increased at 1-week follow-up; MCP-1, positively correlated with gestational age, was elevated at 1-week follow-up. Association modeling between immune markers and microbiome further revealed specific oral microorganisms that are potentially correlated with the host immune response. CONCLUSIONS: PTOR is associated with alteration of the oral microbiome and immune response among a cohort of underserved US pregnant women. Future randomized clinical trials are warranted to comprehensively assess the impact of PTOR on maternal oral flora, birth outcomes, and their offspring's oral health.

External Validation of Risk Factors for Unplanned Hospitalization in Older Adults With Advanced Cancer Receiving Chemotherapy.

BACKGROUND: Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. METHODS: This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. RESULTS: Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0-3, 4-5, and 6-7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04-2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37-3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59-0.71). CONCLUSIONS: The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers. CLINICALTRIALS: gov identifier: NCT02054741.

A compositional mediation model for a binary outcome: Application to microbiome studies.

MOTIVATION: The delicate balance of the microbiome is implicated in our health and is shaped by external factors, such as diet and xenobiotics. Therefore, understanding the role of the microbiome in linking external factors and our health conditions is crucial to translate microbiome research into therapeutic and preventative applications. RESULTS: We introduced a sparse compositional mediation model for binary outcomes to estimate and test the mediation effects of the microbiome utilizing the compositional algebra defined in the simplex space and a linear zero-sum constraint on probit regression coefficients. For this model with the standard causal assumptions, we showed that both the causal direct and indirect effects are identifiable. We further developed a method for sensitivity analysis for the assumption of the no unmeasured confounding effects between the mediator and the outcome. We conducted extensive simulation studies to assess the performance of the proposed method and applied it to real microbiome data to study mediation effects of the microbiome on linking fat intake to overweight/obesity. AVAILABILITY AND IMPLEMENTATION: An R package can be downloaded from https://github.com/mbsohn/cmmb. SUPPLEMENTARY INFORMATION: Supplementary files are available at Bioinformatics online.

Radial Forearm Free Flap Phalloplasty in Female-to-Male Transsexuals - A Comparison Between Gottlieb and Levine's and Chang and Hwang's Technique.

BACKGROUND: Phalloplasty is a crucial part of female-to-male genital gender-affirming surgery, however, up to date, there is still no standardized phalloplasty technique. AIM: To evaluate the outcome of a single-center series of phalloplasties using the free radial forearm flap variations by Chang and Hwang vs by Gottlieb and Levine on a similar number of transgender patients. METHODS: Between 2018 and 2020, 45 female to male transgender patients underwent phalloplasty using a neuro-microvascular free radial forearm flap in our department. Twenty patients underwent phalloplasty by the use of the Chang and Hwang design, whereas 25 patients were subjects to a phalloplasty according to Gottlieb and Levine technique. Patients' demographics, procedural characteristics, postoperative complications, and outcome of both groups were retrospectively evaluated and compared with each other. RESULTS: Patients' demographics were similar in both groups. We did not observe relevant differences concerning postoperative complications comparing the two groups, except for the statistically significant lower rate of partial flap necrosis in the Gottlieb and Levine group. No statistically significant risk factors for an increase in complication rate could be identified. Urethral fistulas were the leading cause of revision. CLINICAL IMPLICATION: Optimizing a phalloplasty surgical technique and contributing to establish the gold standard in phalloplasty. STRENGTHS & LIMITATION: This retrospective study presents the first comparison between the free radial forearm flap phalloplasty by Chang and Hwang and by Gottlieb and Levine performed at the same department on a similar number of transgender patients published so far. CONCLUSION: The Chang and Hwang design is associated with a lower rate of urologic complications (fistulas, stenosis) while the Gottlieb and Levine design has a statistically significant lower incidence of partial flap necrosis. Future prospective trials are needed to establish the gold standard in phalloplasty. Spennato S, Ederer IA., Borisov K et al. Radial Forearm Free Flap Phalloplasty in Female-to-Male Transsexuals - A Comparison Between Gottlieb and Levine's and Chang and Hwang's Technique. J Sex Med 2022;19:661-668.

Predicting Treatment Response with Sensory Phenotyping in Post-Traumatic Neuropathic Pain.

OBJECTIVE: Currently available treatments for neuropathic pain are only modestly efficacious when assessed in randomized clinical trials and work for only some patients in the clinic. Induced-pain or gain-of-function phenotypes have been shown to predict response to analgesics (vs placebos) in patients with neuropathic pain. However, the predictive value of these phenotypes has never been studied in post-traumatic neuropathic pain. METHODS: Mixed-effects models for repeated measures were used to evaluate the efficacy of pregabalin vs placebo in subgroups with induced-pain phenotypes (i.e., hyperalgesia or allodynia) in data from a recent, multinational randomized clinical trial (N = 539) that identified phenotypic subgroups through the use of a structured clinical exam. RESULTS: The difference in mean pain score between the active and placebo groups (i.e., delta) after 15 weeks of treatment for the subgroup with hyperalgesia was -0.76 (P = 0.001), compared with 0.19 (P = 0.47) for the subgroup that did not have hyperalgesia. The treatment-by-phenotype interaction, which tests whether subgroups have statistically different treatment responses, was significant (P = 0.0067). The delta for the subgroup with allodynia was -0.31 (P = 0.22), compared with -0.30 (P = 0.22) for the subgroup that did not have allodynia (treatment-by-phenotype interaction P = 0.98). CONCLUSIONS: These data suggest that hyperalgesia, but not allodynia, predicts response to pregabalin in patients with chronic post-traumatic neuropathic pain. This study extends the growing data supporting the utility of induced-pain phenotypes to predict response to analgesics in post-traumatic neuropathic pain. Sensory phenotyping in large, multisite trials through the use of a structured clinical exam has the potential to accelerate the development of new analgesics and improve the generalizability of clinical trial results.

Measured influence of overhead HVAC on exposure to airborne contaminants from simulated speaking in a meeting and a classroom.

Tracer gas experiments were conducted in a 158 m3 room with overhead supply diffusers to study dispersion of contaminants from simulated speaking in physically distanced meeting and classroom configurations. The room was contained within a 237 m3 cell with open plenum return to the HVAC system. Heated manikins at desks and a researcher operating the tracer release apparatus presented 8-9 thermal plumes. Experiments were conducted under conditions of no forced air and neutral, cooled, or heated air supplied at 980-1100 cmh, and with/out 20% outdoor air. CO2 was released at the head of one manikin in each experiment to simulate small (<5 µm diameter) respiratory aerosols. The metric of exposure relative to perfectly mixed (ERM) is introduced to quantify impacts, based on measurements at manikin heads and at three heights in the center and corners of the room. Chilled or neutral supply air provided good mixing with ERMs close to one. Thermal stratification during heating produced higher ERMs at most manikins: 25% were ≥2.5 and the highest were >5× perfectly mixed conditions. Operation of two within-zone air cleaners together moving ≥400 cmh vertically in the room provided enough mixing to mitigate elevated exposure variations.

Assessing the use of portable air cleaners for reducing exposure to airborne diseases in a conference room with thermal stratification.

The COVID-19 pandemic has highlighted the need for strategies that mitigate the risk of aerosol disease transmission in indoor environments with different ventilation strategies. It is necessary for building operators to be able to estimate and compare the relative impacts of different mitigation strategies to determine suitable strategies for a particular situation. Using a validated CFD model, this study simulates the dispersion of exhaled contaminants in a thermally stratified conference room with overhead heating. The impacts of portable air-cleaners (PACs) on the room airflow and contaminant distribution were evaluated for different PAC locations and flow rates, as well as for different room setups (socially distanced or fully occupied). To obtain a holistic view of a strategy's impacts under different release scenarios, we simultaneously model the steady-state distribution of aerosolized virus contaminants from eight distinct sources in 18 cases for a total of 144 release scenarios. The simulations show that the location of the source, the PAC settings, and the room set-up can impact the average exposure and PAC effectiveness. For this studied case, the PACs reduced the room average exposure by 31%-66% relative to the baseline case. Some occupant locations were shown to have a higher-than-average exposure, particularly those seated near the airflow outlet, and occupants closest to sources tended to see the highest exposure from said source. We found that these PACs were effective at reducing the stratification caused by overhead heating, and also identified at least one sub-optimal location for placing a PAC in this space.

Investigation of HVAC operation strategies for office buildings during COVID-19 pandemic.

To minimize the indoor transmission of contaminants, such as the virus that can lead to COVID-19, buildings must provide the best indoor air quality possible. Improving indoor air quality can be achieved through the building's HVAC system to decrease any concentration of indoor contaminants by dilution and/or by source removal. However, doing so has practical downsides on the HVAC operation that are not always quantified in the literature. This paper develops a temporal simulation capability that is used to investigate the indoor virus concentration and operational cost of an HVAC system for two mitigation strategies: (1) supplying 100% outdoor air into the building and (2) using different HVAC filters, including MERV 10, MERV 13, and HEPA filters. These strategies are applied to a hypothetical medium office building consisting of five occupied zones and located in a cold and dry climate. We modeled the building using the Modelica Buildings library and developed new models for HVAC filtration and virus transmission to evaluate COVID-19 scenarios. We show that the ASHRAE-recommended MERV 13 filtration reduces the average virus concentration by about 10% when compared to MERV 10 filtration, with an increase in site energy consumption of about 3%. In contrast, the use of 100% outdoor air reduces the average indoor concentration by about an additional 1% compared to MERV 13 filtration, but significantly increases heating energy consumption. Use of HEPA filtration increases the average indoor concentration and energy consumption compared to MERV 13 filtration due to the high resistance of the HEPA filter.

Tradeoffs among indoor air quality, financial costs, and CO2 emissions for HVAC operation strategies to mitigate indoor virus in U.S. office buildings.

Adapting building operation during the COVID-19 pandemic to improve indoor air quality (IAQ) while ensuring sustainable solutions in terms of costs and CO2 emissions is challenging and limited in literature. Our previous study investigated different HVAC operation strategies, including increased filtration using MERV 10, MERV 13, or HEPA filters, as well as supplying 100% outdoor air into buildings for a system initially sized for MERV 10 filtration. This paper significantly extends that research by systematically analyzing the potential financial and environmental impact for different locations in the U.S. The previous medium office building system model is improved to account for operation in different climates. New evaluation metrics are created to consider the comprehensive impact of improving IAQ on costs and CO2 emissions, using dynamic emission factors for electricity generation depending on the location. HVAC operation strategies are studied in five different locations across the United States, with distinct climates and electricity sources. In four of the five locations, MERV 13 filtration offers the best improvement in IAQ per increase in costs and emissions relative to MERV 10. The exception is the mildest climate of San Diego, where use of 100% outdoor air provides the best IAQ with a limited increase in costs and emissions. A system not sized for HEPA filtration can lead to increased costs and emissions without much improvement in IAQ.

Measuring Functional Status in Huntington's Disease.

BACKGROUND: Neuropsychiatric and cognitive symptoms account for substantial morbidity in Huntington's disease (HD), but their impact on functional status may not be captured using the Total Functional Capacity (TFC) scale. The objective of this study was to assess the impact of motor, cognitive, and neuropsychiatric symptoms on functional status in persons with HD, comparing two instruments. METHODS: Multiple regression analyses assessed the relationship between neuropsychiatric, cognitive, and motor symptoms and functional status as measured using TFC and Adult Functional Adaptive Behavior (AFAB) scales. RESULTS: Greater burden of neuropsychiatric (P = 0.017), cognitive (P = 0.001), and motor (P = 0.001) symptoms was associated with greater impairments to functional status as measured by the AFAB scale. Only motor symptoms were associated with TFC scores (P = 0.002). The 3 symptom domains explained more of the variance in AFAB than TFC scores (P = 0.016). CONCLUSIONS: TFC may have limited applicability, particularly in early-stage HD patients, as a measure of functional status. The AFAB scale can be used in HD studies as a more holistic measure of functional status. © 2020 International Parkinson and Movement Disorder Society.

Automating the interpretation of PM2.5 time-resolved measurements using a data-driven approach.

The rapid development of automated measurement equipment enables researchers to collect greater quantities of time-resolved data from indoor and outdoor environments. While significant, the interpretation of the resulting data can be a time-consuming effort. This paper introduces an automated process of interpreting PM2.5 time-resolved data and differentiating PM2.5 emissions resulting from indoor and outdoor sources. We use Random Forest (RF), a machine learning approach, to study a dataset of 836 indoor emission events that occurred over a 2-week period in 18 apartments in California. In this paper, we show model development and evaluate its performance as the sample size and source vary. We discuss the characteristics of the dataset that tended to help the source identification and why. For example, we show that data from many events and from different apartments are essential for the model to be suitable for analyzing a new separate dataset. We also show that longitudinal data appear to be more helpful than the time frequency of measurements within a given apartment. We use the resulting RF model to analyze PM2.5 data of an entirely separate dataset collected from 65 new homes in California. The RF model identifies 442 indoor emission events, with only a few misidentifications.

Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap.

BACKGROUND: Constructing a sensitive phallus is a key objective in sex affirmation surgery, but still there is a major lack of evidence in outcome analysis of postoperative sensibility of the newly constructed body part. AIM: To evaluate the innervation and sensibility of a forearm free-flap neophallus with nerve coaptation by a broad-spectrum follow-up. METHODS: The phallic sensibility of 20 transgender individuals who underwent phalloplasty with a free radial forearm flap was evaluated by a standardized multimodal approach, examining 5 main sensory modalities. Measurements were performed in defined areas at the phallus and at the unoperated forearm as a control area. Additionally, all patients were asked to complete a questionnaire about their subjective quality of life and ability to orgasm. OUTCOME: This study evaluated the following parameters: perception of pressure (Semmes-Weinstein monofilaments) and vibration (C64 Hz tuning fork), static two-point discrimination, sharp-blunt and hot-cold discrimination at the phallus and the forearm, sum score of calculated life satisfaction, and ability to orgasm. RESULTS: Most of the patients (n = 14) were able to perceive 2 or more sensory modalities tested at the newly constructed phallus. 2 patients did not develop any sensibility. Interestingly, the median values for vibration perception were similar for the phallus and the unoperated forearm. Pressure sensibility was present at the phallus, but less than at the forearm. Moreover, sharp-blunt sensibility was present in 11 patients. In contrast, clear cold-warm discrimination could not be achieved, although the majority of patients detected the cold stimulus. A two-point discrimination of up to 23 mm could not be detected in either body part. 15 patients experienced orgasms without difficulty after 23 months (n = 20 after 54 months). CLINICAL IMPLICATIONS: We observed successful recovery of sensibility at the phalli for the majority of patients, including the preservation of orgasm. STRENGTHS & LIMITATIONS: Our institution is one of the few centers regularly performing phalloplasties in transgender patients, especially preferring the technique of Gottlieb and Levine. This study contributes to the few studies that perform sensory testing at the phallus and is unique in its kind in that it uses a multimodal approach. A limitation of this study is the limited number of cases and the limited validity of vibratory testing. CONCLUSION: Confirming a promising tactile sensibility after phalloplasty with a neurovascular radial forearm flap, the next step would be to identify whether this reinnervation effectively develops due to nerve coaptation or spontaneous sprouting. Küenzlen L, Nasim S, van Neerven S, et al. Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap. J Sex Med 2020;17:1012-1024.

Air Pollutant Emission Rates for Dry Anaerobic Digestion and Composting of Organic Municipal Solid Waste.

Dry anaerobic digestion (AD) of organic municipal solid waste (MSW) followed by composting of the residual digestate is a waste diversion strategy that generates biogas and soil amendment products. The AD-composting process avoids methane (CH4) emissions from landfilling, but emissions of other greenhouse gases, odorous/toxic species, and reactive compounds can affect net climate and air quality impacts. In situ measurements of key sources at two large-scale industrial facilities in California were conducted to quantify pollutant emission rates across the AD-composting process. These measurements established a strong relationship between flared biogas ammonia (NH3) content and emitted nitrogen oxides (NOx), indicating that fuel NOx formation is significant and dominates over the thermal or prompt NOx pathways when biogas NH3 concentration exceeds ∼200 ppm. Composting is the largest source of CH4, carbon dioxide (CO2), nitrous oxide (N2O), and carbon monoxide (CO) emissions (∼60-70%), and dominate NH3, hydrogen sulfide (H2S), and volatile organic compounds (VOC) emissions (>90%). The high CH4 contribution to CO2-equivalent emissions demonstrates that composting can be an important CH4 source, which could be reduced with improved aeration. Controlling greenhouse gas and toxic/odorous emissions from composting offers the greatest mitigation opportunities for reducing the climate and air quality impacts of the AD-composting process.

Estimates of pollutant temporal and spatial variability in commercial buildings from the joint urban 2003 field experiments.

In this paper, we report on the indoor concentrations from a suite of full-scale outdoor tracer-gas point releases conducted in the downtown area of Oklahoma City in 2003. A point release experiment consisted of releases of sulfur hexafluoride (SF6 ) in multiple buildings and from different outdoor locations. From the measurements, we are able to estimate the concentration variations indoors for a building operating under "typical" operating conditions. The mean indoor spatial coefficients of variation are 30% to 45% from a daytime outdoor release are around 80% during an outdoor evening release. Having estimates of the spatial coefficient of variation provides stakeholders, including first responders, with the likely range of concentrations in the building when little is known about the building characteristics and operating behavior, such as developing urban-scale hazard and consequence analyses. We show differences in indoor measurements at different distances to the release points, floors of the building, and heating, ventilation, and air conditioning system (HVAC) operation. We also show estimates at different time resolutions. The statistics show that in the studied medium to large commercial buildings, spatial differences would result in peak indoor concentrations in certain parts of the buildings that may be substantially higher than the building average. To our knowledge, very few tracer gas measurements have been conducted in buildings of this scope, particularly with measurements on multiple floors and within a floor. The resulting estimates of spatial variability provide a unique opportunity for hazard assessment, and comparison to multi-zone models.

A GLM-based latent variable ordination method for microbiome samples.

Distance-based ordination methods, such as principal coordinates analysis (PCoA), are widely used in the analysis of microbiome data. However, these methods are prone to pose a potential risk of misinterpretation about the compositional difference in samples across different populations if there is a difference in dispersion effects. Accounting for high sparsity and overdispersion of microbiome data, we propose a GLM-based Ordination Method for Microbiome Samples (GOMMS) in this article. This method uses a zero-inflated quasi-Poisson (ZIQP) latent factor model. An EM algorithm based on the quasi-likelihood is developed to estimate parameters. It performs comparatively to the distance-based approach when dispersion effects are negligible and consistently better when dispersion effects are strong, where the distance-based approach sometimes yields undesirable results. The estimated latent factors from GOMMS can be used to associate the microbiome community with covariates or outcomes using the standard multivariate tests, which can be investigated in future confirmatory experiments. We illustrate the method in simulations and an analysis of microbiome samples from nasopharynx and oropharynx.

Phalloplasty in Female-to-Male Transsexuals by Gottlieb and Levine's Free Radial Forearm Flap Technique-A Long-Term Single-Center Experience Over More than Two Decades.

BACKGROUND: The free radial forearm flap phalloplasty is the most utilized method for penile reconstruction. Among the techniques described in the literature, evidence for the flap design after Gottlieb and Levine is poor. METHODS: From January 1993 until December 2015, 402 phalloplasties were performed in our clinic. Among the 247 free radial forearm flap phalloplasties, 232 free radial forearm flap phalloplasties were performed after Gottlieb and Levine in 229 patients. Operation and patient-specific characteristics were evaluated. RESULTS: This study presents the highest number of free radial forearm flap phalloplasties after Gottlieb and Levine. The rate of total flap failure was 3%; 46% of the patients were heavy smokers. Urinary fistulae and strictures are common. The revision rate for urinary fistulae and/or strictures was 1.3 per patient. The number of postoperative complications, such as bleeding (14.2%), thrombosis of the flap requiring revision (11.2%), or delayed wound healing (16.8%) was considering the high rate of nicotine abuse (45.9%) reasonable. CONCLUSION: The free radial forearm phalloplasty in the design by Gottlieb and Levine is well established at our institution and has proven safe and reliable since 1993. The operative results are satisfactory for both patients and surgeons even in the presence of relevant comorbidities and heavy smoking. We acknowledge the long ordeal and psychological pressure that our patients suffer from, before presenting in our outpatient clinic.

A robust approach for identifying differentially abundant features in metagenomic samples.

MOTIVATION: The analysis of differential abundance for features (e.g. species or genes) can provide us with a better understanding of microbial communities, thus increasing our comprehension and understanding of the behaviors of microbial communities. However, it could also mislead us about the characteristics of microbial communities if the abundances or counts of features on different scales are not properly normalized within and between communities, prior to the analysis of differential abundance. Normalization methods used in the differential analysis typically try to adjust counts on different scales to a common scale using the total sum, mean or median of representative features across all samples. These methods often yield undesirable results when the difference in total counts of differentially abundant features (DAFs) across different conditions is large. RESULTS: We develop a novel method, Ratio Approach for Identifying Differential Abundance (RAIDA), which utilizes the ratio between features in a modified zero-inflated lognormal model. RAIDA removes possible problems associated with counts on different scales within and between conditions. As a result, its performance is not affected by the amount of difference in total abundances of DAFs across different conditions. Through comprehensive simulation studies, the performance of our method is consistently powerful, and under some situations, RAIDA greatly surpasses other existing methods. We also apply RAIDA on real datasets of type II diabetes and find interesting results consistent with previous reports. AVAILABILITY AND IMPLEMENTATION: An R package for RAIDA can be accessed from http://cals.arizona.edu/%7Eanling/sbg/software.htm.

A two-stage statistical procedure for feature selection and comparison in functional analysis of metagenomes.

MOTIVATION: With the advance of new sequencing technologies producing massive short reads data, metagenomics is rapidly growing, especially in the fields of environmental biology and medical science. The metagenomic data are not only high dimensional with large number of features and limited number of samples but also complex with a large number of zeros and skewed distribution. Efficient computational and statistical tools are needed to deal with these unique characteristics of metagenomic sequencing data. In metagenomic studies, one main objective is to assess whether and how multiple microbial communities differ under various environmental conditions. RESULTS: We propose a two-stage statistical procedure for selecting informative features and identifying differentially abundant features between two or more groups of microbial communities. In the functional analysis of metagenomes, the features may refer to the pathways, subsystems, functional roles and so on. In the first stage of the proposed procedure, the informative features are selected using elastic net as reducing the dimension of metagenomic data. In the second stage, the differentially abundant features are detected using generalized linear models with a negative binomial distribution. Compared with other available methods, the proposed approach demonstrates better performance for most of the comprehensive simulation studies. The new method is also applied to two real metagenomic datasets related to human health. Our findings are consistent with those in previous reports. AVAILABILITY: R code and two example datasets are available at http://cals.arizona.edu/∼anling/software.htm. SUPPLEMENTARY INFORMATION: Supplementary file is available at Bioinformatics online.

Does gadolinium-based contrast material improve diagnostic accuracy of local invasion in rectal cancer MRI? A multireader study.

OBJECTIVE. The purpose of this study was to compare reader accuracy and agreement on rectal MRI with and without gadolinium administration in the detection of T4 rectal cancer. MATERIALS AND METHODS. In this study, two radiologists and one fellow independently interpreted all posttreatment MRI studies for patients with locally advanced or recurrent rectal cancer using unenhanced images alone or combined with contrast-enhanced images, with a minimum interval of 4 weeks. Readers evaluated involvement of surrounding structures on a 5-point scale and were blinded to pathology and disease stage. Sensitivity, specificity, negative predictive value, positive predictive value, and AUC were calculated and kappa statistics were used to describe interreader agreement. RESULTS. Seventy-two patients (38 men and 34 women) with a mean age of 61 years (range, 32-86 years) were evaluated. Fifteen patients had 32 organs invaded. Global AUCs without and with gadolinium administration were 0.79 and 0.77, 0.91 and 0.86, and 0.83 and 0.78 for readers 1, 2, and 3, respectively. AUCs before and after gadolinium administration were similar. Kappa values before and after gadolinium administration for pairs of readers ranged from 0.5 to 0.7. CONCLUSION. On the basis of pathology as a reference standard, the use of gadolinium during rectal MRI did not significantly improve radiologists' agreement or ability to detect T4 disease.

Accurate genome relative abundance estimation for closely related species in a metagenomic sample.

BACKGROUND: Metagenomics has a great potential to discover previously unattainable information about microbial communities. An important prerequisite for such discoveries is to accurately estimate the composition of microbial communities. Most of prevalent homology-based approaches utilize solely the results of an alignment tool such as BLAST, limiting their estimation accuracy to high ranks of the taxonomy tree. RESULTS: We developed a new homology-based approach called Taxonomic Analysis by Elimination and Correction (TAEC), which utilizes the similarity in the genomic sequence in addition to the result of an alignment tool. The proposed method is comprehensively tested on various simulated benchmark datasets of diverse complexity of microbial structure. Compared with other available methods designed for estimating taxonomic composition at a relatively low taxonomic rank, TAEC demonstrates greater accuracy in quantification of genomes in a given microbial sample. We also applied TAEC on two real metagenomic datasets, oral cavity dataset and Crohn's disease dataset. Our results, while agreeing with previous findings at higher ranks of the taxonomy tree, provide accurate estimation of taxonomic compositions at the species/strain level, narrowing down which species/strains need more attention in the study of oral cavity and the Crohn's disease. CONCLUSIONS: By taking account of the similarity in the genomic sequence TAEC outperforms other available tools in estimating taxonomic composition at a very low rank, especially when closely related species/strains exist in a metagenomic sample.