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PubMed2006

Benchmarking DNA barcodes: An assessment using available primate sequences.

DNA barcoding has been recently promoted as a method for both assigning specimens to known species and for discovering new and cryptic species. Here we test both the potential and the limitations of DNA barcodes by analysing a group of well-studied organisms--the primates. Our results show that DNA barcodes provide enough information to efficiently identify and delineate primate species, but that they cannot reliably uncover many of the deeper phylogenetic relationships. Our conclusion is that these short DNA sequences do not contain enough information to build reliable molecular phylogenies or define new species, but that they can provide efficient sequence tags for assigning unknown specimens to known species. As such, DNA barcoding provides enormous potential for use in global biodiversity studies.

Animals↗
PubMed2004

Benchmarking a test of temporal orientation with data from american and taiwanese persons with Alzheimer's disease and american normal elderly.

Orientation questions are readily incorporated into longitudinal population surveys, but their value as a screening tool for cognitive impairment is uncertain. We evaluated the screening value of four orientation-to-time items (TTO) from the Mini-Mental State Examination (MMSE) by determining their association with full-scale MMSE scores. Data collected under protocols with strict eligibility criteria in the US (64 normal elderly, 242 persons with probable Alzheimer's disease) and Taiwan (241 persons with probable Alzheimer's disease) were analyzed. The TTO and full-scale MMSE scores were significantly correlated (p < 0.05) in persons with a Clinical Dementia Rating (CDR) score of 0 or 1; this was not significant in persons with a CDR of >1 (p > 0.05). Both TTO and MMSE were significantly associated with education in persons with 0-7 years of education; some MMSE items, but none of the TTO items, were associated with education in persons with more than 7 years of education. TTO may be a useful component of cognitive screening efforts.

Aged↗
PubMed2026

Benchmarking urinary cell transcriptomes for noninvasive differentiation of BK polyomavirus-associated nephropathy from T cell-mediated rejection.

BK polyomavirus-associated nephropathy (BKVN) adversely impacts kidney allograft survival and often mimics acute T cell-mediated rejection (TCMR), confounding diagnosis and management. To address this conundrum, we performed unbiased RNA sequencing of urinary cells matched to biopsies classified as BKVN with intragraft inflammation (BKVN-P), BKVN without inflammation (BKVN-N), TCMR, or no rejection (NR). BKVN-N displayed dominant host DNA replication, cell cycle, and repair programs, while BKVN-P samples exhibited expansive innate immune activation, antigen presentation, chemokine upregulation, and epithelial injury. Both BKVN subtypes shared signatures of T cell exhaustion and mature and tolerogenic dendritic cell activation but differed in immune orientation - Th1 predominance in BKVN-N versus Treg and CD8 enrichment in BKVN-P. Compared with TCMR samples, BKVN-P lacked robust TCR/CD28 signaling and was enriched for viral and innate modules; BKVN-N lacked alloimmune activation. B cell exhaustion characterized BKVN-N, while BKVN-P displayed robust B cell activation with metabolic downregulation. A ratiometric urinary cell biomarker, CXCL10 mRNA/CD3E mRNA, distinguished both BKVN subtypes from TCMR with diagnostic accuracy, replicated by quantitative reverse transcription PCR for clinical translation, and confirmed in an independent cohort. These findings demonstrate the utility of urinary cell transcriptomics for resolving viral injury from alloimmunity, enabling precision diagnostics and targeted immunomodulation in kidney transplantation.

Humans↗
PubMed2006

Benchmarking ortholog identification methods using functional genomics data.

BACKGROUND: The transfer of functional annotations from model organism proteins to human proteins is one of the main applications of comparative genomics. Various methods are used to analyze cross-species orthologous relationships according to an operational definition of orthology. Often the definition of orthology is incorrectly interpreted as a prediction of proteins that are functionally equivalent across species, while in fact it only defines the existence of a common ancestor for a gene in different species. However, it has been demonstrated that orthologs often reveal significant functional similarity. Therefore, the quality of the orthology prediction is an important factor in the transfer of functional annotations (and other related information). To identify protein pairs with the highest possible functional similarity, it is important to qualify ortholog identification methods. RESULTS: To measure the similarity in function of proteins from different species we used functional genomics data, such as expression data and protein interaction data. We tested several of the most popular ortholog identification methods. In general, we observed a sensitivity/selectivity trade-off: the functional similarity scores per orthologous pair of sequences become higher when the number of proteins included in the ortholog groups decreases. CONCLUSION: By combining the sensitivity and the selectivity into an overall score, we show that the InParanoid program is the best ortholog identification method in terms of identifying functionally equivalent proteins.

Algorithms↗
PubMed2006

Benchmarks for designing two-stage studies using modified mini-mental state examinations: experience from the Women's Health Initiative Memory Study.

BACKGROUND: The most efficient approach for studies examining the incidence of dementia involves a brief screening instrument to identify participants for more extensive testing to identify cognitive impairment. The modified mini-mental state examination (3MS) is commonly used as this initial screen in such two-stage designs, however its properties for this role require further study. PURPOSE: We use data from the Women's Health Initiative Memory Study to contrast design options in two-stage designs. METHODS: This trial enrolled 7251 participants with nine or more years of education who were aged 65-79 and followed an average of four to five years. Logistic regression was used to examine the case yields at varying two-stage 3MS cutpoints. The efficiency of using different examination schedules and restricting enrollment to higher risk women was examined. RESULTS: Probable dementia is associated with marked decline in 3MS scores. The percentages of women classified with probable dementia ranged from 7.95% (3MS 85-88) to 50.0% (3MS < 70). The numbers [95% confidence interval] of enrolled women necessary to detect one case of probable dementia (four-year follow-up) for baseline 3MS scores of 100, 95, 90 and 85 were estimated as 1477 [389, 5618], 253 [134, 481], 53 [34, 85], and 14 [9, 23], respectively. Compared to annual testing, administration every two years increased the number of required enrollees by 11%, but decreased the number of test administrations by 46%. LIMITATIONS: Our findings are influenced by the characteristics of our study group, its rates of retention, and the study protocol, and may not fully generalize to other settings. CONCLUSIONS: The 3MS can serve as an efficient basis for two-stage study designs and a cutpoint of < or = 88 is reasonable for populations with similar characteristics. Studies may improve efficiency by using the 3MS during screening to eliminate women with low risk for dementia and by conducting testing every two years.

Aged↗
PubMed2025

Refined and benchmarked homemade media for cost-effective, weekend-free human pluripotent stem cell culture.

BACKGROUND: Cost-effective, practical, and reproducible culture of human pluripotent stem cells (hPSCs) is required for basic and translational research. Basal 8 (B8) has emerged as a cost-effective solution for weekend-free and chemically-defined hPSC culture. However, the requirement to home-produce some recombinant growth factors for B8 can hinder access and reproducibility. Moreover, we found the published B8 formulation suboptimal in widely-used normoxic hPSC culture. Lastly, the performance of B8 in functional applications such as genome editing or organoid differentiation required systematic evaluation. METHODS: We formulated B8 with commercially available, growth factors and adjusted its composition to support normoxic culture of WTC11 human induced pluripotent stem cell line. We compared this formulation (B8+) with commercial Essential 8 (cE8) and a home-made, weekend-free E8 formulation (hE8). We measured pluripotency marker expression and cell cycle by flow cytometry, and investigated the transcriptional profiles by bulk and single-cell RNA sequencing. We further assessed genomic stability, genome editing efficiency, single-cell cloning, and differentiation in both monolayer and organoids. Finally, we validated key findings using male (H1) and female (H9) human embryonic stem cells. RESULTS: hE8 performed comparably to cE8 across most functional assays and cell lines. In contrast, cells in B8+ displayed higher NANOG expression and improved genome editing efficiency. At the same time, B8+ led to gene expression changes indicative of marked lineage priming, reflected in altered morphology and differential response to some differentiation protocols. Both weekend-free media resulted in a modest transcriptional shift towards a less metabolically active state, consistent with intermittent media starvation. CONCLUSIONS: Homemade weekend-free media can provide a cost-effective alternative to commercial formulations. hE8, integrating some features of B8 while resembling cE8, emerges as a robust and practical option with limited compromises. B8+, though advantageous in some contexts, warrants caution due to lineage priming effects that may impact differentiation outcomes.

hiPSC; pluripotency; culture media; thermostable F↗
PubMed2004

Benchmarking lung cancer mortality rates in current and former smokers.

STUDY OBJECTIVES: To develop and validate a model for estimating the risk of lung cancer death in current and former smokers. The model is intended for use in analyzing a population of subjects who are undergoing lung cancer screening or receiving lung cancer chemoprevention, to determine whether the intervention has altered lung cancer mortality. DESIGN/SETTING/PATIENTS: Model derivation was based on analyses of the placebo arm of the Carotene and Retinol Efficacy Trial. Model validation was based on analyses of three other longitudinal cohorts. MEASUREMENTS: Observed and predicted number of deaths due to lung cancer. RESULTS: In internal validation, the model was highly concordant and well calibrated. In external validation, the model predictions were similar to what was observed in all of the validation analyses. The predicted and observed deaths within 6 years were very similar when assessed in the Johns Hopkins Hospital trial of chest radiography and sputum cytology screening (176 predicted, 184 observed, p = 0.53), the Memorial Sloan-Kettering Cancer Center trial of chest radiography and sputum cytology screening (108 predicted, 114 observed, p = 0.57), and the National Health and Nutrition Evaluation Survey part I (24 predicted, 21 observed, p = 0.52). CONCLUSIONS: The number of lung cancer deaths in a population of current or former smokers can be accurately predicted, making model-based evaluations of prevention and early detection interventions a useful adjunct to definitive randomized trials. We illustrate this potential use with a small example.

Adult↗
PubMed2003

Benchmark studies of the effectiveness of structural and internal materials as radiation shielding for the international space station.

Accelerator-based measurements and model calculations have been used to study the heavy-ion radiation transport properties of materials in use on the International Space Station (ISS). Samples of the ISS aluminum outer hull were augmented with various configurations of internal wall material and polyethylene. The materials were bombarded with high-energy iron ions characteristic of a significant part of the galactic cosmic-ray (GCR) heavy-ion spectrum. Transmitted primary ions and charged fragments produced in nuclear collisions in the materials were measured near the beam axis, and a model was used to extrapolate from the data to lower beam energies and to a lighter ion. For the materials and ions studied, at incident particle energies from 1037 MeV/nucleon down to at least 600 MeV/nucleon, nuclear fragmentation reduces the average dose and dose equivalent per incident ion. At energies below 400 MeV/nucleon, the calculation predicts that as material is added, increased ionization energy loss produces increases in some dosimetric quantities. These limited results suggest that the addition of modest amounts of polyethylene or similar material to the interior of the ISS will reduce the dose to ISS crews from space radiation; however, the radiation transport properties of ISS materials should be evaluated with a realistic space radiation field.

Aluminum↗
PubMedDate not supplied

Some benchmark searches for testing search capabilities and medical coverage of internet discovery tools.

The past few years have seen a proliferation of search engines for the World Wide Web (WWW), as well as a growing number of specialized subject directories geared to the needs of health care professionals. Yet documentation on scope, coverage, and search features is often uneven at best; and even documented search features may not perform as advertised. This paper will present a group of sample searches to assist users in gauging database size, determining default search operators, and testing for the presence of advanced search features such as case sensitivity, stemming, and concept mapping for medical topics on English-language web sites.

Databases, Factual↗
PubMed1998

Teaching basic skills to children with Down syndrome and developmental delays: the relative efficacy of interactive modeling with social rewards for benchmark achievements and passive observation.

In interventions attempting to remediate deficiencies in the skills repertoire of developmentally delayed children, no less than in medical interventions, it may be fairly said that less is more. That is, the instructor should intervene as little as possible both from the perspective of efficient instructional practice and from time allotment concerns which modern classrooms face. Evidence from this laboratory has indicated that in skills training for children with severe developmental delays the passive observation of a model demonstrating the target skill is more effective than interactive modeling involving hand-over-hand instruction with verbal prompting. We have considered the role of verbal prompting in interactive modeling and have found that prompts intended to provide typical social reinforcers are counterproductive (e.g., Biederman, Davey, Ryder, & Franchi, 1994). The present study examines the efficacy of hand-over-hand modeling with response-contingent verbal prompts. In such instruction, tasks are divided into identifiable sequential components, and the achievement of each component is marked by the delivery of some form of verbal prompt. In a within-subjects design, children were trained in one skill with response-contingent verbal prompts and in a second skill with simple passive observation. A separate group of children were trained with less rigorous verbal prompting in one skill and with passive observation in a second. Consistent with previous research, we found that passive modeling was overall significantly more effective than hand-over-hand modeling and moreover that passive modeling was significantly more effective than hand-over-hand modeling with response-contingent prompting. Our evidence therefore indicates that current classroom practice in training basic skills to children with severe developmental delays may require reassessment in that simple observation of modeled skills appears to be more effective than more labor-intensive instruction.

Achievement↗