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The SARS-CoV-2 Integrated Genomic Epidemiology Database (IGED): Linking viral genomes with patient-level metadata to advance statewide genomic surveillance in California.

In July 2021, the California Code of Regulations Title 17 required all laboratories performing SARS‑CoV‑2 whole genome sequencing (WGS) to report their sequencing results to the California Department of Public Health (CDPH). These viral genomic data and patient metadata were compiled into the Integrated Genomic Epidemiology Database (IGED). Linking anonymized viral sequences with patient‑level information enabled monitoring of infectiousness, pathogenicity, transmission dynamics, evolution, and vaccine evasion among emerging SARS‑CoV‑2 lineages. Laboratories performing SARS-CoV-2 WGS transmitted sequencing results to CDPH through Electronic Laboratory Reporting (ELR) and non-ELR pathways. CDPH applied uniform reporting requirements but allowed flexibility in specific data formats to accommodate diverse data systems. To preserve data quality and interoperability across heterogeneous sources, CDPH implemented standardization, validation, and deduplication protocols. Snowflake, a cloud‑based data storage and analytics platform, and Posit Connect, a cloud deployment and automation platform, supported the management, processing, and integration of data within the IGED. The IGED established links between SARS‑CoV‑2 WGS data and epidemiologic metadata for 801,418 sequences, representing 81.7% of all sequences reported in California. Lineages reported to the IGED showed strong concordance with lineage proportions in GISAID. Sequences reported to the IGED had average turnaround times longer than one month, and the majority of sequencing was performed in Southern California and Los Angeles. The IGED enhanced genomic surveillance through predictive modeling and monitoring concerning evolutionary trends such as recombination and saltations in persistent infections. Development of the IGED highlighted the need for standardized data requirements, sustained funding for sequencing, incentives for data submission, and interdisciplinary collaboration to build an effective genomic surveillance system. This framework for linking genomic and epidemiologic data has not only generated critical insights for SARS‑CoV‑2 but also provided the foundation for CDPH and other public health organizations to develop similar IGED‑like systems for other priority pathogens as genomic surveillance expands.

Journal Article

Digital and computational morphology in hematology: current platforms, clinical evidence, and future requirements.

INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.

artificial intelligence

Evaluation of home glucose measuring devices.

A large number of glucose-monitoring systems suitable for home use are now available. The Glucochek, an early model (Mk I) and a later (Mk II), the Stan Clark RAHC, the Glucometer, and 20-800 BM glycemie strips were evaluated with regard to accuracy, precision, model variability and operator variability before a particular system was recommended for patient use. Whole blood glucose, on samples samples taken in the Diabetic Clinic of The Royal Melbourne Hospital, Melbourne, was measured with the system under test and in the Biochemistry Department. Accuracy was indicated by the mean of the differences between the two results, and precision by the standard deviation of these differences-the closer these results to zero, the better the system. The 20-800 BM Glycemia strips gave the best results in the hands of an experienced operator, but showed the greatest interoperator differences. These differences decreased when a machine-based system was employed. The Glucochek Mk I did not perform satisfactorily. All the systems tested showed a marked decrease in accuracy and precision when blood glucose levels were greater than 15.0 mmol/L. These results show that a machine is not a necessary part of a home glucose-monitoring system; that patients on home glucose-monitoring must be trained and their results checked against a reference method initially and, ideally, at regular intervals; that home glucose-monitoring in patients with marked hyperglycaemia unreliable.

Blood Glucose

PheBee: A Graph-Aware System for Scalable, Traceable, and Semantic Phenotyping.

OBJECTIVES: Phenotype-driven workflows in clinical and translational research require standardized ontology-based representation, ontology-aware cohort discovery, and provenance inspection for each assertion. Existing approaches optimize either for semantic traversal or scalable batch analytics, but not both. We describe PheBee, a hybrid system that links semantic assertions to scalable evidence storage via a deterministic identifier, preserving provenance while supporting ontology-aware discovery at cohort scale. MATERIALS AND METHODS: PheBee represents phenotype assertions in a knowledge graph as ontology-linked nodes with clinical modifier context (e.g., negated, family history), and stores supporting evidence records in a scalable row-oriented evidence table for cohort-scale access. The two layers are connected by a deterministic identifier enabling stable joins across repeated ingestions without duplicating high-volume evidence in the graph. We evaluated PheBee using synthetic datasets designed to exercise end-to-end ingestion and query workflows. RESULTS: Functional evaluation validated hierarchical term expansion, qualifier-aware retrieval, duplicate-free assertion handling under re-ingestion, and privacy-conscious management of subjects shared across multiple research projects. At scale (10,000 subjects producing 12M evidence records) PheBee completed ingestion in ~30 minutes and responded to interactive queries within 6 seconds under concurrent load. DISCUSSION: PheBee exposes a unified API for ontology-aware cohort discovery with hierarchical term expansion, subject-centric retrieval of phenotypes and clinical modifiers, and evidence and provenance queries. Its data model aligns with GA4GH Phenopackets, facilitating interoperability with phenotype exchange standards. CONCLUSION: By combining ontology-aware semantics with scalable, provenance-bearing evidence storage, PheBee provides a practical open-source foundation for phenotype-driven research workflows that demand both semantic precision and cohort-scale traceability.

cohort studies

OmicsPred as a centralised resource for genetic prediction of multi-omic traits.

Genetic prediction of multi-omic data has emerged as a cost-effective alternative to direct omics profiling, particularly useful for identifying molecular features associated with disease susceptibility. However, despite its popularity, multi-omic imputation models are fragmented across studies, hindering findability, accessibility, interoperability and re-use. To address this, we developed OmicsPred (https://www.omicspred.org), a centralised platform for the deposition and dissemination of genetic prediction models of multi-omic traits. OmicsPred unifies the most commonly used molecular imputation models (e.g. from PredictDB) and other published studies totalling 3,339,469 prediction models spanning transcriptomic, proteomic, and metabolomic traits (as of May 2026). Each model is accompanied by metadata describing score development and predictive performance, and distributed in formats compatible with popular analytic tools, such as PGS Catalog Calculator and MetaXcan. To demonstrate the utility of the resource for systematic target discovery, we perform a multi-omic phenome-wide association analysis in Million Veterans Program data.

Journal Article

From Infection Control to Healthcare System Resilience: Lessons Learned from SARS-CoV-2 Research in Healthcare Workers.

The COVID-19 pandemic placed unprecedented pressure on healthcare systems and exposed healthcare workers (HCWs) to biological hazards, organizational pressures, and psychological strain. Evidence generated during the emergency shows that HCW protection cannot rely on isolated measures, but requires an integrated framework combining epidemiological surveillance, contact tracing, infection prevention and control, vaccination, occupational health, and workforce support. Contact tracing helped identify occupational exposures and clarify how duration, proximity, and inadequate use of personal protective equipment jointly shaped infection risk. Subsequent studies of reinfection showed that susceptibility reflected the interaction of viral circulation, individual immunity, and vaccination status. Vaccination reduced the clinical impact of SARS-CoV-2 and supported service continuity, although uptake depended on trust, communication, and management of adverse event concerns. The pandemic also highlighted substantial economic consequences and a high burden of psychological distress and burnout among HCWs. Building on this evidence, future preparedness should translate these lessons into permanent, adaptable infrastructure rather than temporary emergency arrangements, integrating interoperable, AI-assisted surveillance capable of combining occupational, diagnostic, vaccination, and genomic data to detect emerging risks early, while ensuring robust data governance and human oversight. Equally central is the need to address long-term workforce vulnerabilities, including Long COVID, attrition, and burnout, through early identification, rehabilitation, flexible return-to-work models, and sustained psychosocial support. Achieving this requires structured multidisciplinary collaboration among occupational medicine, infection control, epidemiology, mental health, and digital health specialists, moving from fragmented infection-control protocols to an integrated, proactive, and learning-oriented preparedness strategy. Protecting HCWs is therefore not only an occupational safety priority but a foundational prerequisite for safe, equitable, and sustainable healthcare delivery during future infectious threats.

Humans

Cardiac output determinations in the newborn. Reproducibility of the pulsed Doppler velocity measurement.

Cardiac output (QAo) can be estimated noninvasively by pulsed Doppler (PD) ultrasonographic determination of mean ascending aortic blood flow velocity (VAo) combined with M-mode echocardiographic determination of ascending aortic cross sectional area (AAo). Cardiac output is calculated from the volumetric flow equation (QAo) = (VAo) X (AAo). Pulsed Doppler measurements are known to correlate well with Fick and thermodilution methods; however, inter- and intraoperator variability of the velocity component of the PD method has not been determined in newborns. We did three repeated PD measures of mean aortic flow velocity in ten term infants (using four trained operators) to determine inter- and intraoperator reproducibility. The coefficient of variation for intraoperator variability (random error) for a single measurement of VAo was 11.7%. If three repeated measures by a single operator were averaged, the random error was 7.0%. There was little interoperator variability found.

Aorta

Single-operator comparison of early and mid-second-trimester amniocentesis.

We sought to determine whether early amniocentesis is a safe and acceptable method of genetic evaluation in early pregnancy. During the 54-month period from September 1986 to February 1991, 300 consecutive early second-trimester amniocenteses were performed transabdominally at 13-14 weeks' gestation and 567 consecutive mid-second-trimester transabdominal amniocenteses were performed at 16-18 weeks. Group assignment was nonrandomized, interoperator-dependent variables were eliminated, and analysis was performed in one cytogenetics laboratory. The median maternal age and indications for the procedure were similar in both groups. There were no significant differences between the early- and mid-second-trimester amniocenteses in failed sampling, ambiguous results, pregnancy loss from 4 weeks after the procedure to 28 weeks' gestation, preterm birth, or perinatal death rate. Pregnancy loss within 4 weeks of amniocentesis was more frequent in early- than in mid-second-trimester amniocenteses. We conclude that early amniocentesis is a safe and acceptable method of genetic evaluation.

Adult

A study of variance in densitometry of retinal nerve fiber layer photographs in normals and glaucoma suspects.

The main object of this research was to develop a reliable method of screening glaucoma suspects and patients for early loss of or changes in the retinal nerve fiber layer (RNFL). This study quantifies the variances due to photography, digitizing, and analysis of red-free photographs of the RNFL. The influence of pupil size, optic disc position and eye movements, film processing, digitizing, and intra- and interphotographic-session and intra- and interoperator variances were established. It was found that pupils needed to be dilated to at least 6 mm, that the optic disc had to be positioned in a standardized area in the negative, that the head of the subject had to remain still during photography, and that film processing and digitizing of the negative needed to be strictly controlled to minimize the variance in collection of densitometry data from RNFL red-free photographs. It was established that focusing of the negatives during digitization was not crucial. Criteria were defined for acceptable negatives. Interphotographic-session and intraoperator variances were not significant in most cases when negatives were digitized to these criteria. Analysis of interphotographic-session variance showed that there were still some factors in photography, film processing, and/or image digitizing that were not sufficiently controlled for long-term follow-up without normalization of the data. Densitometry data gathered using the established protocol, from negatives of 71 subjects were analyzed; best sensitivity and specificity rates of 80% and 100%, respectively, were achieved for the diagnosis of glaucoma.

Adult

Investigation of variable factors in drilling bone.

Experiments were conducted to investigate the pressures that are exerted on drills during the preparation of bone. Twenty operators used six different types of drills at high and low speeds to prepare standardized holes and slots in animal bone. The peak vertical forces exerted varied between 5.98 and 24.32 newtons (x = 12.45 newtons). The mean vertical forces varied between 4.22 and 18.93 newtons (x = 9.16 newtons). Spear point and twist drills were associated with significantly lower operating pressures and shorter operating times than round and fissure burs. These differences, however, were much less than the interoperator variations.

Animals

Human left main coronary artery blood flow: noninvasive Doppler echocardiography with sample volume tracking.

We developed sample volume tracking units that controlled the pulsed ultrasonic Doppler sample volume location in relation with the anterior-posterior movement of the human left main coronary artery (LMCA). Combined with noninvasive Doppler echocardiographic mechanical sector scanners (DS), the trackers controlled the axial location of the sample volume by range gate control. The Doppler angle was minimized with the long axis of the imaged LMCA. Both stored waveform, memory-driven (MD) and real-time (RT) trackers were developed. These devices were used to measure blood velocity spectral waveforms and lumen diameters, which were used to calculate flow. Using the RT tracker, we compared DS measurements with known flows (0-1000 ml/min) in a moving 4 mm tygon tubing phantom (r = 0.92, SEE = 32 ml/min). Using the MD tracker, we compared the DS with simultaneous invasive flow measurements in 11 patients with angiographically normal coronaries and ventricular function during cardiac catheterization. Using the RT tracker, we compared the DS measurements with subsequent nonsimultaneous, invasive flow data in 8 similar patients. Invasively determined flows were calculated from angiographic diameters and blood velocities which were obtained with a Doppler velocimeter catheter. Regression coefficients (r) were: (Table: see text). V = maximum velocity, D = diameter, Q = mean flow, *p less than .05 Interoperator and intraoperator variabilities in vivo of DS measurements with RT tracking were 21% and 15%, respectively. We conclude that Doppler echocardiography with either MD or RT sample volume tracking may be of limited clinical usefulness in the noninvasive measurement of phasic left main coronary artery blood flow in unselected patients.

Angiocardiography

A decentralized future for the open-science databases.

The continuous and reliable open access to curated biological data repositories is indispensable for accelerating rigorous scientific inquiry and fostering reproducible research outcomes. However, the current paradigm, which relies heavily on centralized infrastructure for the storage and distribution of foundational biomedical datasets, inherently introduces significant vulnerabilities. This centralized model is susceptible to single points of failure, including cyberattacks, technical malfunctions, natural disasters, and even political or funding uncertainties. Such disruptions can lead to widespread data unavailability, data loss, integrity compromises, and substantial delays in critical research, ultimately impeding scientific progress. The downstream effect of such interruptions can be the widespread paralysis of diverse research activities, including computational, clinical, molecular, and climate studies. This scenario vividly illustrates the inherent dangers of consolidating essential scientific resources within a single geopolitical or institutional locus. As data generation is accelerating and the global landscape continues to fluctuate, the sustainability of centralized models must be critically re-evaluated. A shift toward federated and decentralized architectures may offer a robust and forward-looking approach to enhancing the resilience of scientific data infrastructures by reducing exposure to governance instability, infrastructural fragility, and funding volatility, while also promoting equity and global accessibility. Inspired by established models such as ELIXIR's federated infrastructure and the policy and funding frameworks developed by CODATA and the Global Biodata Coalition (GBC), emerging Decentralized Science (DeSci) initiatives can contribute to building more resilient, fair, and incentive-aligned data ecosystems. The future of open science depends on integrating these complementary approaches to establish a globally distributed, economically sustainable, and institutionally robust infrastructure that safeguards scientific data as a public good, further ensuring continued accessibility, interoperability, and preservation for generations to come. Here, we examine the structural limitations of centralized repositories, evaluate federated and decentralized models, and propose a hybrid framework for resilient, fair, and sustainable scientific data stewardship.

data accessibility

Needle size and sample adequacy in ultrasound-guided biopsy of thyroid nodules.

OBJECTIVES: To determine the optimal needle size (23-gauge or 27-gauge) for ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and to compare the interoperator yield for this procedure. PATIENTS AND METHOD: Over an 11-month period, 123 patients underwent biopsy of a thyroid nodule. Three experienced radiologists were assigned at random to sample the nodules. For each nodule, four passes were performed in random order, two with 23-gauge needles and two with 27-gauge needles. If a specific pass yielded no tissue or blood, as determined by visual inspection (i.e., the sample was dry), the procedure was repeated until a satisfactory sample was obtained. After each patient had left the department, the aspirates were reviewed by a cytopathologist (who was not aware of needle size or operator identity) to determine diagnostic adequacy. RESULTS: Among the 123 nodules, 88 were solid, and 35 were complex cysts. There was no significant difference between the two sizes of needle in the adequacy of the samples obtained (102 nodules were adequately sampled with the 23-gauge needle and 95 with the 27-gauge needle; McNemar chi 2 test, p = 0.1456). However, there were significantly fewer dry passes with the larger needle (2 with the 23-gauge needle and 16 with the 27-gauge needle; chi 2 test, p = 0.0022). Sixteen nodules were inadequately sampled with both needles. Eight of these were less than 1 cm in greatest dimension. Only one solid nodule greater than 1 cm in greatest dimension was inadequately sampled. There was no difference in yield among the three radiologists (chi 2 test, p = 0.5192). No significant complications were encountered. CONCLUSIONS: Needles of both 23 and 27 gauge can be used to obtain fine-needle aspiration biopsy samples from thyroid nodules. Using both sizes is recommended, because the number of dry passes is lower with the larger needle, but the diagnostic quality of the aspirate may be better with the smaller one. Experienced physicians can perform fine-needle aspiration biopsy with equal proficiency.

Adult

Assessment of the periotest device in baseline mobility measurements of craniofacial implants.

The present study aimed to evaluate reliability of the Periotest instrument in baseline mobility measurement of craniofacial implants in a human wet bone specimen. Sixteen 4.0-mm craniofacial Brånemark implants were placed in the most common sites for craniofacial implant placement. A 5.5-mm abutment was attached to each implant except one in the mastoid bone, which was connected with a bone-anchored hearing aid (BAHA) abutment. Baseline Periotest values (PTVs) were recorded on each abutment at different vertical measurement points by three different clinicians using three Periotest devices. Baseline PTVs for each abutment ranged between -1.23 and -5.90. Interoperator and interinstrumental variability did not influence PTVs; however, the vertical measurement point on the abutment proved to have a strong effect on PTV recordings.

Aged