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Fundamentals of FAIR biomedical data analyses in the cloud using custom pipelines.

As the biomedical data ecosystem increasingly embraces the findable, accessible, interoperable, and reusable (FAIR) data principles to publish multimodal datasets to the cloud, opportunities for cloud-based research continue to expand. Besides the potential for accelerated and diverse biomedical discovery that comes from a harmonized data ecosystem, the cloud also presents a shift away from the standard practice of duplicating data to computational clusters or local computers for analysis. However, despite these benefits, researcher migration to the cloud has lagged, in part due to insufficient educational resources to train biomedical scientists on cloud infrastructure. There exists a conceptual lack especially around the crafting of custom analytic pipelines that require software not pre-installed by cloud analysis platforms. We here present three fundamental concepts necessary for custom pipeline creation in the cloud. These overarching concepts are workflow and cloud provider agnostic, extending the utility of this education to serve as a foundation for any computational analysis running any dataset in any biomedical cloud platform. We illustrate these concepts using one of our own custom analyses, a study using the case-parent trio design to detect sex-specific genetic effects on orofacial cleft (OFC) risk, which we crafted in the biomedical cloud analysis platform CAVATICA.

Cloud Computing↗

Matching point clouds: limits and possibilities.

In computer-aided production of fixed dental restorations, the process chain always starts with digitizing, independent of the type of further (data) processing, the material used, and the kind of restoration to be produced. The quality of the digitized data, followed by the influences of further data processing and the production parameters, decisively influence the fitting accuracy of the dental restoration to be fabricated. The accuracy with which individually measured 3D data sets in the form of point clouds can be matched for further processing in one common system of coordinates was the object of the present study. Casts of the maxilla and mandible were digitized in several partial measurements comprising two to three teeth in each case, using an optical three-coordinate measuring system. The individual segments were sequentially aligned to surfaces that were created on the basis of partial point clouds. The mean deviation between surfaces and point clouds was between 1.90 microns and 18.24 microns. The accuracy of the alignment was determined by the RMS (root mean square) error, and was on average 14.2 microns (SD 7 microns) for the maxilla and 17.2 microns (SD 9.4 microns) for the mandible. Combining a larger number of smaller segments did not improve the result, since the errors of the individual registrations are summed in sequential matching. In this study, the errors arising in matching are not negligible and can possibly negatively influence the quality (fitting accuracy) of the restoration produced on the basis of the matched data records.

Analog-Digital Conversion↗

The Gabriella Miller Kids First Data Resource for genomic research in pediatric cancer and congenital anomalies.

Nine-year-old brain tumor patient Gabriella Miller challenged members of Congress to "stop talking and start doing" when providing federal funding for research into cures for pediatric cancer and congenital anomalies. Though she ultimately lost her life to that cancer, her advocacy efforts resulted in the 2014 Gabriella Miller Kids First Research Act, launching the Gabriella Miller Kids First Pediatric Research Program at the National Institutes of Health (NIH). The overarching goal of the Gabriella Miller Kids First Pediatric Research Program is to help researchers uncover new insights into the biology of childhood cancer and congenital anomalies. Following the signing of the Gabriella Miller Kids First Research Act 2.0 in January 2025, the program has been extended at NIH through 2028 to advance the groundwork laid in the program's first ten years. The Gabriella Miller Kids First Data Resource Center has since honored her legacy by building a comprehensive data resource for genomic research into pediatric conditions. Data from more than 30,000 participants annotated with demographic and clinical information related to their diagnoses have been released for secondary research and analysis using the center's web-based platforms. This paper analyzes the outcomes of the initiative and highlights breakthroughs made by the larger research community resulting from the availability of this data resource. We explore the future expansion of the data resource to include new modalities and tools for supporting life-saving research for children like Gabriella Miller.

Humans↗

The relationships between personal PM exposures for elderly populations and indoor and outdoor concentrations for three retirement center scenarios.

Personal exposures, indoor and outdoor concentrations, and questionnaire data were collected in three retirement center settings, supporting broader particulate matter (PM)--health studies of elderly populations. The studies varied geographically and temporally, with populations studied in Baltimore, MD in the summer of 1998, and Fresno, CA in the winter and spring of 1999. The sequential nature of the studies and the relatively rapid review of the mass concentration data after each segment provided the opportunity to modify the experimental designs, including the information collected from activity diary and baseline questionnaires and influencing factors (e.g., heating, ventilation, and air-conditioning (HVAC) system operation, door and window openings, air exchange rate) measurements. This paper highlights both PM2.5 and PM10 personal exposure data and interrelationships across the three retirement center settings, and identifies the most probable influencing factors. The current limited availability of questionnaire results, and chemical speciation data beyond mass concentration for these studies, provided only limited capability to estimate personal exposures from models and apportion the personal exposure collections to their sources. The mean personal PM2.5 exposures for the elderly in three retirement centers were found to be consistently higher than the paired apartment concentrations by 50% to 68%, even though different facility types and geographic locations were represented. Mean personal-to-outdoor ratios were found to 0.70, 0.82, and 1.10, and appeared to be influenced by the time doors and windows were open and aggressive particle removal by the HVAC systems. Essentially identical computed mean PM2.5 personal clouds of 3 micrograms/m3 were determined for two of the studies. The proposed significant contributing factors to these personal clouds were resuspended particles from carpeting, collection of body dander and clothing fibers, personal proximity to open doors and windows, and elevated PM levels in nonapartment indoor microenvironments.

Aerosols↗

Solar UV dose patterns in Italy.

Since 1992 solar ultraviolet (UV) spectral irradiance (290-325 nm) has been measured at two Italian stations of Rome (urban site) and Ispra (semirural site) using Brewer spectrophotometry. The data collected under all sky conditions, are compared with the output of a sophisticated radiative transfer model (System for Transfer of Atmospheric Radiation--STAR model). The STAR multiple scattering scheme is able to cope with all physical processes relevant to the UV transfer through the atmosphere. The experience so far acquired indicates that, in spite of the unavoidable uncertainties in the input parameters (ozone, aerosol, surface albedo, pressure, temperature, relative humidity, cloud cover), measured and computed clear sky iradiances are in reasonable agreement. The STAR model is applied to build up the solar UV geographic patterns in Italy: the daily dose in the range 290-325 nm is computed at about 70 sites where a thorough and homogeneous climatology is available. For each month the concept of an idealized "standard day" is introduced and the surface distribution of solar UV field determined. The map of solar UV patterns for Italy, available for the first time, meets the study requirements in the field of skin and eye epidemiology, as well as in other investigations dealing with the impact of UV on the biosphere. The results are interpreted in terms of atmospheric and meteorological parameters modulating UV radiation reaching the ground.

Eye↗

Small scale model for CFD validation in DAF application.

A laboratory model is used to measure the generic flow patterns in dissolved air flotation (DAF). The Perspex model used in this study allows the use of laser Doppler velocimetry (LDV), a non-invasive, high-resolution (+/- 2 mm s-1) laser technique of flow velocity measurement. Measurement of flow velocity in the single-phase situation was first carried out. Air-saturated water was then supplied to the tank and measurements of bubble velocity in the two-phase system were made. Vertical flow re-circulation was observed in the flotation zone. In the bottom of the flotation zone (near the riser) secondary flow re-circulation was observed, but only in the two-phase system. Another phenomenon was the apparent movement of flow across the tank width, which may be due to lateral dispersion of the bubble cloud. Data from preliminary computational fluid dynamics (CFD) models were compared against this measured data in the case of the single-phase system. The CFD model incorporating a k-epsilon model of turbulence was found to give closer agreement with the measured data than the corresponding laminar flow model. The measured velocity data will be used to verify two-phase computational fluid dynamics (CFD) models of DAF.

Air↗

Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity.

The hypothetical model is built explaining the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo. The protective layer of the polymer on the liposome surface is considered as a statistical 'cloud' of polymer possible conformations in solution. Computer simulation was used to demonstrate that relatively a small number of liposome-grafted molecules of hydrophilic and flexible polymer can create a dense protective conformational cloud over the liposome surface preventing opsonizing protein molecules from contacting liposome. A more rigid polymer fails to form this dense protective cloud, even when hydrophilic. Computer simulation was also used to reveal possible heterogeneity of reactive sites on a polymer-coated liposome surface, and to estimate the optimal polymer-to-lipid ratio for efficient liposome protection. Experiments have been performed with the quenching of liposome-associated fluorescent label (nitrobenzoxadiazole or fluorescein) with protein (rhodamine-ovalbumin or anti-fluorescein antibody) from solution. It was shown that poly(ethylene glycol) grafting to liposomes hinders protein interaction with the liposome surface, whereas liposome-grafted dextran (more rigid polymer) in similar quantities does not affect protein-liposome interaction. Highly-reactive and low-reactive populations of chemically identical reactive sites have been found on polymer-coated liposomes. Experimental data satisfactory confirm the suggested mechanism for the longevity of polymer-modified liposome.

Binding Sites↗

The Primary Electroviscous Effect: Thin Double Layers (akappa>>1) and a Stern Layer.

The primary electroviscous effect due to the charge clouds surrounding spherical charged particles suspended in an electrolyte was studied by Hinch and Sherwood (J. Fluid Mech. 132, 337 (1983)) in the limit of double layers thin compared to the particle radius a. Here we introduce the effect of a dynamic Stern layer into that analysis, in order to explain the numerical results of Rubio-Hernández et al. (J. Colloid Interface Sci. 206, 334 (1998)) in terms of the ratio of the tangential ionic fluxes within the charge cloud to those within the Stern layer. The predictions of the asymptotic analysis are compared with those of numerical computations. The thickness of the charge cloud is characterized by the Debye length kappa(-1). If akappa>10 the predictions of the asymptotic analysis exhibit the same qualitative behavior as the numerical results, but akappa>1000 is required to achieve quantitative agreement to within 2.5%. Copyright 2000 Academic Press.

Journal Article↗

CoSAG-nf: A Scalable Nextflow Pipeline for Co-assembly, Optimization, and Interactive Visualization of High-Throughput Single-Cell Genomes.

MOTIVATION: Single-cell amplified genomes (SAGs) are crucial for resolving intra-population microbial heterogeneity and accurately understanding the metabolic potential of microbial dark matter populations. However, SAGs generated through multiple displacement amplification (MDA) of genomic DNA from single cells with single-copy chromosomes are highly fragmented and prone to contamination, severely hindering high-quality genome reconstruction and functional analysis, which greatly limits their scientific utility. Co-assembly of related SAGs can substantially improve genome quality, but to our knowledge no automated pipeline exists for high-throughput processing, forcing manual implementation of complex workflows that scale poorly to modern dataset sizes. RESULTS: We present CoSAG-nf, an automated high-throughput co-assembly and optimization pipeline for SAGs, implemented following the nf-core framework standards. The pipeline performs alignment-free clustering using sourmash MinHash signatures, then employs iterative tetranucleotide frequency profiling to identify and exclude outlier SAGs from co-assembly groups. CheckM2 quality assessment guides dynamic selection of optimal SAG combinations to optimize genome completeness and minimize contamination. Fully containerized, CoSAG-nf ensures reproducibility and scalability for the high-throughput processing of large-scale SAG datasets across diverse computing environments, including HPC and cloud platforms. The pipeline generates comprehensive HTML reports with quality metrics and taxonomic annotations, providing an end-to-end solution for automated high-throughput single-cell genome reconstruction. AVAILABILITY: CoSAG-nf is freely available under the MIT License at: https://github.com/linfengxu/CoSAG-nf. Archival code repository snapshots are published at zenodo with doi: https://doi.org/10.5281/zenodo.21525244. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Journal Article↗

Non-convulsive status epilepticus as cause for focal neurological deficit.

In a four-and-a-half year period, 19 patients with focal neurological deficits accompanied by a focal electrographic status epilepticus were encountered. Sixteen of these patients showed clouding of consciousness or confusion. Computed tomography of the brain revealed focal lesions in 15 patients. In 7 patients the lesions were the result of a recent cerebral event and in 8 patients they were long-standing. All patients were treated with anti-epileptic drugs. Ten of the 12 patients without an acute lesion showed a complete recovery in a few days. In these patients the symptoms may have been caused by the continuous seizure activity, classifying them as cases of non-convulsive focal status epilepticus. Only 2 of the 7 patients with an acute lesion had a full recovery. In patients with an acute lesion the part played by the electrographic status epilepticus in the acquired deficits is unclear. Continuous or frequent intermittent focal epileptic discharges on the EEG may warrant treatment with anti-epileptic drugs in patients with focal neurological deficits, even when one of the hallmarks of epilepsy, clonic movements, is absent.

Adult↗

Three-dimensional documentation of wound healing: first results of a new objective method for measurement.

BACKGROUND: The objective assessment of wound healing is one essential parameter of quality assurance in a modern chronic wound management program. In the past assessment has been based exclusively on a two-dimensional measurement of the wound surface with planimetry or digital photo documentation in combination with such measurements. An objective method for measuring the volume of chronic wounds has not yet been available. PATIENTS AND METHODS: In cooperation with the company RSI, we linked digital photography, optical raster by means of digital scanner, and picture processing software (DigiSkin) for an exact three-dimensional image of chronic wounds. The generated point clouds allow the visual, computer-assisted three-dimensional quantification and can document the course of healing of chronic wounds. RESULTS: In comparison to currently available systems, our new method makes possible the objective measurement of volume changes and wound healing course in chronic wounds.We demonstrate the utility of the system in reference to three patients with chronic venous leg ulcers. CONCLUSIONS: Using this new, objective three-dimensional wound measurement system,it is possible to reliably quantify changes in wound healing for the first time. Future clinical studies have a new option for the gathering of data which will facilitate evidenced-based conclusions.

Aged↗

Petrous apicitis. Clinical considerations.

Although petrous apicitis was a frequent occurrence in the first half of this century, it has become an uncommon disease because of the widespread use of antibiotics for otitis media. In this series of eight cases of petrous apicitis it is evident that petrositis cannot be equated with Gradenigo's triad (otitis, abducens paralysis, and deep pain) since none of the cases manifested with the classical syndrome. Abducens paralysis was seen in only two of the eight cases. Deep facial or ear pain was present in four of the eight cases and appeared to be the most useful symptom in the diagnosis of petrositis. Four of the eight cases were discovered only after previous, unsuccessful surgical procedures. Chronic petrous apicitis may be occult and manifest only after failure to control suppuration by conventional tympanomastoid surgery. When petrositis is suspected, conventional x-ray study may show bone erosion and asymmetric clouding of the petrous tip. Computed tomographic scanning was most useful in the delineation of bone destruction and of the apex. When the diagnosis of petrous apicitis is made, aggressive surgical drainage is indicated.

Adolescent↗

Fedflow: cloud orchestration for federated learning with the FeatureCloud platform.

MOTIVATION: Federated learning (FL) enables collaborative model training on geographically distributed genomic and clinical datasets while complying with data privacy laws and regulatory constraints. FeatureCloud is an existing platform for FL that provides an accessible web-based interface and a large repository of implemented methods. However, due to its graphical interface, FeatureCloud requires manual interaction of all participants, limiting automation, iteration, and reproducibility. RESULTS: We introduce fedflow, a Python-based command-line tool for headless orchestration of FL tasks with FeatureCloud. This tool uses distributed computing resources such as virtual machines or cloud instances to automate such workflows. This allows for scalable federated computing either in local simulations or deployed in a trusted environment. Further, we demonstrate how fedflow can be used to integrate FeatureCloud in reproducible Snakemake workflows. For this, we reanalyse a metagenomic dataset with two federated algorithms and compare the results to the centralized approach with pooled data. Overall, fedflow enables automation of multi-client FL tasks, facilitates embedding of FeatureCloud in standard bioinformatics pipelines and thereby helps increase reproducibility. AVAILABILITY: Fedflow is open-source and available at https://github.com/W-L/fedflow.

Journal Article↗

[A scanning method for the dental casts of intercuspal position].

OBJECTIVE: To acquire the 3D point-cloud of the dental casts of intercuspal position and rebuild it in computer. METHODS: A special scanning method was used to acquire the point-cloud of dental cast by using the D.02-L-3D SCANNER and rebuild the model by computer. RESULTS: The method could acquire a 3D model with high resolving power and clear-cut dental anatomic configuration for the dental casts of intercuspal position. CONCLUSION: This is a viable method of scanning with many advantages, such as precision, simplicity, high efficiency. It could satisfy the requirements of clinical practice, teaching and scientific research.

Cuspid↗

The Greenhouse effect: impacts of ultraviolet-B (UV-B) radiation, carbon dioxide (CO2), and ozone (O3) on vegetation.

There is a fast growing and an extremely serious international scientific, public and political concern regarding man's influence on the global climate. The decrease in stratospheric ozone (O3) and the consequent possible increase in ultraviolet-B (UV-B) is a critical issue. In addition, tropospheric concentrations of 'greenhouse gases' such as carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4) are increasing. These phenomena, coupled with man's use of chlorofluorocarbons (CFCs), chlorocarbons (CCs), and organo-bromines (OBs) are considered to result in the modification of the earth's O3 column and altered interactions between the stratosphere and the troposphere. A result of such interactions could be the global warming. As opposed to these processes, tropospheric O3 concentrations appear to be increasing in some parts of the world (e.g. North America). Such tropospheric increases in O3 and particulate matter may offset any predicted increases in UV-B at those locations. Presently most general circulation models (GCMs) used to predict climate change are one- or two-dimensional models. Application of satisfactory three-dimensional models is limited by the available computer power. Recent studies on radiative cloud forcing show that clouds may have an excess cooling effect to compensate for a doubling of global CO2 concentrations. There is a great deal of geographic patchiness or variability in climate. Use of global level average values fails to account for this variability. For example, in North America: 1. there may be a decrease in the stratospheric O3 column (1-3%); however, there appears to be an increase in tropospheric O3 concentrations (1-2%/year) to compensate up to 20-30% loss in the total O3 column; 2. there appears to be an increase in tropospheric CO2, N2O and CH4 at the rate of roughly 0.8%, 0.3% and 1-2%, respectively, per year; 3. there is a decrease in erythemal UV-B; and 4. there is a cooling of tropospheric air temperature due to radiative cloud forcing. The effects of UV-B, CO2 and O3 on plants have been studied under growth chamber, greenhouse and field conditions. Few studies, if any, have examined the joint effects of more than one variable on plant response. There are methodological problems associated with many of these experiments. Thus, while results obtained from these studies can assist in our understanding, they must be viewed with caution in the context of the real world and predictions into the future. Biomass responses of plants to enhanced UV-B can be negative (adverse effect); positive (stimulatory effect) or no effect (tolerant). Sensitivity rankings have been developed for both crop and tree species. However, such rankings for UV-B do not consider dose-response curves. There are inconsistencies between the results obtained under controlled conditions versus field observations. Some of these inconsistencies appear due to the differences in responses between cultivars and varieties of a given plant species; and differences in the experimental methodology and protocol used. Nevertheless, based on the available literature, listings of sensitive crop and native plant species to UV-B are provided. Historically, plant biologists have studied the effects of CO2 on plants for many decades. Experiments have been performed under growth chamber, greenhouse and field conditions. Evidence is presented for various plant species in the form of relative yield increases due to CO2 enrichment. Sensitivity rankings (biomass response) are agein provided for crops and native plant species. However, most publications on the numerical analysis of cause-effect relationships do not consider sensitivity analysis of the mode used. Ozone is considered to be the most phytotoxic regional scale air pollutant. In the pre-occupation of loss in the O3 column, any increases in tropospheric O3 concentrations may be undermined relative to vegetation effects. As with the other stress factors, the effects of O3 have been studied both under controlled and field conditions. Thboth under controlled and field conditions. The numerical explanation of cause-effect relationships of O3 is a much debated subject at the present time. Much of the controversy is directed toward the definition of the highly stochastic, O3 exposure dynamics in time and space. Nevertheless, sensitivity rankings (biomass response) are provided for crops and native vegetation. The joint effects of UV-B, CO2 and O3 are poorly understood. Based on the literature of plant response to individual stress factors and chemical and physical climatology of North America, we conclude that nine different crops may be sensitive to the joint effects: three grain and six vegetable crops (sorghum, oat, rice, pea, bean, potato, lettuce, cucumber and tomato). In North America, we consider Ponderosa and loblolly pines as vulnerable among tree species. This conclusion should be moderated by the fact that there are few, if any, data on hardwood species. In conclusion there is much concern for global climate change and its possible effects on vegetation. While this is necessary, such a concern and any predictions must be tempered by the lack of sufficient knowledge. Experiments must be designed on an integrated and realistic basis to answer the question more definitively. This would require very close co-operation and communication among scientists from multiple disciplines. Decision makers must realize this need.

Journal Article↗

Comparison of respirable dust specifications with recent lung data.

This paper compares the two major respirable dusts size specifications with lung models derived from a recent review using computer simulation in logarithmic normal dust clouds. It was found that either specification gives reasonable reproductibility with respect to either the nose or mouth breathing lung models over the usual range of industrial dust clouds, and either could be chosen as a standard with only a slight adjustment in the corresponding dust control limit.

Air Pollutants, Occupational↗

The lids influence on corneal shape.

BACKGROUND: The lids are in contact to the corneal surface in normal viewing. Refractive surgery, however, is performed with a speculum in place and thus the lids are not in contact with the cornea. PURPOSE: To investigate central corneal shape with and without the lids touching the corneal surface. METHODS: The technique consists of exporting the point cloud of the topography scanner into computer software that recreates the corneal surface. The technique of surface modeling was used to form central corneal elevation height difference maps of four normal eyes with and without lid contact to the corneal surface. RESULTS: Surface modeling demonstrated the trend that the lids influence the corneal shape. CONCLUSION: The lids distort corneal shape.

Cornea↗