Deep learning model for pleural effusion detection via active learning and pseudo-labeling: a multisite study.

BACKGROUND: The study aimed to develop and validate a deep learning-based Computer Aided Triage (CADt) algorithm for detecting pleural effusion in chest radiographs using an active learning (AL) framework. This is aimed at addressing the critical need for a clinical grade algorithm that can timely diagnose pleural effusion, which affects approximately 1.5 million people annually in the United States. METHODS: In this multisite study, 10,599 chest radiographs from 2006 to 2018 were retrospectively collected from an institution in Taiwan to train the deep learning algorithm. The AL framework utilized significantly reduced the need for expert annotations. For external validation, the algorithm was tested on a multisite dataset of 600 chest radiographs from 22 clinical sites in the United States and Taiwan, which were annotated by three U.S. board-certified radiologists. RESULTS: The CADt algorithm demonstrated high effectiveness in identifying pleural effusion, achieving a sensitivity of 0.95 (95% CI: [0.92, 0.97]) and a specificity of 0.97 (95% CI: [0.95, 0.99]). The area under the receiver operating characteristic curve (AUC) was 0.97 (95% DeLong's CI: [0.95, 0.99]). Subgroup analyses showed that the algorithm maintained robust performance across various demographics and clinical settings. CONCLUSION: This study presents a novel approach in developing clinical grade CADt solutions for the diagnosis of pleural effusion. The AL-based CADt algorithm not only achieved high accuracy in detecting pleural effusion but also significantly reduced the workload required for clinical experts in annotating medical data. This method enhances the feasibility of employing advanced technological solutions for prompt and accurate diagnosis in medical settings.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Functional connectivity for the language network in the developing brain: 30 weeks of gestation to 30 months of age.

Although the neural scaffolding for language is putatively present before birth, the maturation of functional connections among the key nodes of the language network, Broca's and Wernicke's areas, is less known. We leveraged longitudinal and cross-sectional data from three sites collected through six studies to track the development of functional circuits between Broca's and Wernicke's areas from 30 weeks of gestation through 30 months of age in 127 unique participants. Using resting-state fMRI data, functional connectivity was calculated as the correlation between fMRI time courses from pairs of regions, defined as Broca's and Wernicke's in both hemispheres. The primary analysis evaluated 23 individuals longitudinally imaged from 30 weeks postmenstrual age (fetal) through the first postnatal month (neonatal). A secondary analysis in 127 individuals extended these curves into older infants and toddlers. These data demonstrated significant growth of interhemispheric connections including left Broca's and its homolog and left Wernicke's and its homolog from 30 weeks of gestation through the first postnatal month. In contrast, intrahemispheric connections did not show significant increases across this period. These data represent an important baseline for language systems in the developing brain against which to compare those neurobehavioral disorders with the potential fetal onset of disease.

Effect of prophylactic tube feeding in head and neck cancer patients with high Mallampati score undergoing definitive concurrent chemoradiotherapy.

PURPOSE: There is no consensus on the selection of appropriate prophylactic tube feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the effect of prophylactic tube feeding in patients with HNSCC who presented with a high Mallampati score and underwent CCRT. METHODS: We prospectively enrolled 185 consecutive patients with stage II to IVa HNSCC and a pre-treatment Mallampati score of 3 or 4 who received CCRT between August 2017 and December 2018 with follow-up data collected retrospectively. Patients were divided to either with or without prophylactic tube feeding group for comparison of treatment tolerance, toxicities, and quality of life(QOL). Propensity score matching (PSM) was used to achieve balanced covariates across the two groups. RESULTS: Of the cohort, 52 (28.1%) and 133 (71.9%) patients were allocated to the prophylactic and non-prophylactic tube feeding groups, respectively. Before and after PSM, patients in the tube feeding group had a significantly lower incidence of incomplete radiotherapy, incompletion of chemotherapy, emergency room visits, and grade 3 or higher infection, and improved symptoms of quality of life after CCRT than those in the non-tube feeding group. CONCLUSION: Prophylactic tube feeding was associated with better treatment tolerance, safety profiles, and quality of life in patients with HNSCC and high Mallampati scores who underwent CCRT. Therefore, Mallampati score might serve as a clinical tool for proactive selection of patients receiving prophylactic tube feeding in HNSCC patients upon receiving CCRT.

Modeling local coronavirus outbreaks.

This article presents an overview of methods developed for the modeling and control of local coronavirus outbreaks. The article reviews early transmission dynamics featuring exponential growth in infections, and links this to a renewal epidemic model where the current incidence of infection depends upon the expected value of incidence randomly lagged into the past. This leads directly to simple formulas for the fraction of the population infected in an unmitigated outbreak, and reveals herd immunity as the solution to an optimization problem. The model also leads to direct and easy-to-understand formulas for aligning observable epidemic indicators such as cases, hospitalizations and deaths with the unobservable incidence of infection, and as a byproduct leads to a simple first-order approach for estimating the effective reproduction number R t . The model also leads naturally to direct assessments of the effectiveness of isolation in preventing the spread of infection. This is illustrated with application to repeat asymptomatic screening programs of the sort utilized by universities, sports teams and businesses to prevent the spread of infection.

Changes in fatigue among cancer patients before, during, and after radiation therapy: A meta-analysis.

BACKGROUND: Fatigue is a common symptom in cancer patients receiving radiotherapy. However, previous studies report inconsistent patterns of fatigue change. AIM: The aim of this study was to estimate changes in fatigue among patients with cancer before, during, and after radiotherapy. METHODS: Five databases (PubMed, SDOL, CINAHL Plus with Full Text, Medline [ProQuest], and ProQuest Dissertations) were searched for studies published from January 2006 to May 2021. Three effect sizes of fatigue change (immediate, short-term, and long-term) were calculated for each primary study using standardized mean difference. A random-effect model was used to combine effect sizes across studies. Subgroup analyses and meta-regression were performed to identify potential categorical and continuous moderators, respectively. RESULTS: Sixty-five studies were included in this meta-analysis. The weighted mean effect size for immediate, short-term, and long-term effects was 0.409 (p < .001; 95% CI [0.280, 0.537]), 0.303 (p < .001; 95% CI [0.189, 0.417]), and 0.201 (p = .05; 95% CI [-0.001, 0.404]), respectively. Studies with prostate cancer patients had a significantly higher short-term (0.588) and long-term weight mean effect size (0.531) than studies with breast (0.128, -0.072) or other cancers (0.287, 0.215). Higher radiotherapy dosage was significantly associated with a higher effect size for both immediate (ß = .0002, p < .05) and short-term (ß = .0002, p < .05) effect. LINKING EVIDENCE TO ACTION: Findings from this meta-analysis indicated that radiotherapy-induced fatigue (RIF) exist for more than 3 months after the completion of treatment. Assessment of radiation-induced fatigue in cancer patients should extend long after treatment completion, especially for patients with prostate cancer and patients receiving a higher radiation dose. Interventions to reduce fatigue tailored for different treatment phases may be developed.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

An empirical Bayesian ranking method, with applications to high throughput biology.

MOTIVATION: In bioinformatics, genome-wide experiments look for important biological differences between two groups at a large number of locations in the genome. Often, the final analysis focuses on a P-value-based ranking of locations which might then be investigated further in follow-up experiments. However, this strategy may result in small effect sizes, with low P-values, being ranked more favorably than larger more scientifically important effects. Bayesian ranking techniques may offer a solution to this problem provided a good prior distribution for the collective distribution of effect sizes is available. RESULTS: We develop an Empirical Bayes ranking algorithm, using the marginal distribution of the data over all locations to estimate an appropriate prior. In simulations and analysis using real datasets, we demonstrate favorable performance compared to ordering P-values and a number of other competing ranking methods. The algorithm is computationally efficient and can be used to rank the entirety of genomic locations or to rank a subset of locations, pre-selected via traditional FWER/FDR methods in a 2-stage analysis. AVAILABILITY AND IMPLEMENTATION: An R-package, EBrank, implementing the ranking algorithm is available on CRAN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hypothyroidism and risks of cerebrovascular complications among patients with head and neck cancer after radiotherapy.

BACKGROUND: Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. METHODS: Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. RESULTS: 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. CONCLUSIONS: Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.

Repeat SARS-CoV-2 testing models for residential college populations.

Residential colleges are considering re-opening under uncertain futures regarding the COVID-19 pandemic. We consider repeat SARS-CoV-2 testing models for the purpose of containing outbreaks in the residential campus community. The goal of repeat testing is to detect and isolate new infections rapidly to block transmission that would otherwise occur both on and off campus. The models allow for specification of aspects including scheduled on-campus resident screening at a given frequency, test sensitivity that can depend on the time since infection, imported infections from off campus throughout the school term, and a lag from testing until student isolation due to laboratory turnaround and student relocation delay. For early- (late-) transmission of SARS-CoV-2 by age of infection, we find that weekly screening cannot reliably contain outbreaks with reproductive numbers above 1.4 (1.6) if more than one imported exposure per 10,000 students occurs daily. Screening every three days can contain outbreaks providing the reproductive number remains below 1.75 (2.3) if transmission happens earlier (later) with time from infection, but at the cost of increased false positive rates requiring more isolation quarters for students testing positive. Testing frequently while minimizing the delay from testing until isolation for those found positive are the most controllable levers for preventing large residential college outbreaks. A web app that implements model calculations is available to facilitate exploration and consideration of a variety of scenarios.

Comparison of 18F-FDG PET/MRI, MRI, and 18F-FDG PET/CT for the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

PURPOSE: In this prospective study, we sought to compare the clinical utility of fluorodeoxyglucose PET/MRI, MRI, and PET/CT in the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: We examined 198 consecutive patients with biopsy-proven OHSCC who agreed to receive chemoradiation. All patients underwent pretreatment PET/MRI and PET/CT on the same day. Patients were followed-up for a minimum of 12 months or until death. The McNemar's test and receiver-operating characteristic (ROC) curves were used to compare sensitivity/specificity and the diagnostic capabilities of PET/MRI, MRI, and PET/CT, respectively. RESULTS: We identified 55 patients (27.7%) who had synchronous cancers and/or distant metastases (number of involved sites: 83). The results of site-based analysis revealed that the sensitivity of PET/MRI was 15.7% higher than that of MRI (73.5% versus 57.8%, p < 0.001) and 3.6% higher compared with PET/CT (73.5% versus 69.9%, p = 0.083), whereas the sensitivity of PET/CT was 12.1% higher than that of MRI (69.9% versus 57.8%, p = 0.012). On a patient-basis, ROC curve analysis demonstrated that PET/MRI yielded a greater area under curve than MRI (0.930 versus 0.905, p = 0.023). There were no significant differences in terms of diagnostic capability between MRI and PET/CT (0.905 versus 0.917, p = 0.469) and between PET/MRI and PET/CT (0.930 versus 0.917, p = 0.062). CONCLUSIONS: In our cohort, PET/MRI showed a significantly higher diagnostic capability than MRI and no significant difference compared with PET/CT for the detection of synchronous cancers or distant metastases in patients with OHSCC.

A scoping review of medical education research for residents in radiation oncology.

BACKGROUND: Both medical education and radiation oncology have progressed significantly in the past decade, but a generalized overview of educational research for radiation oncology residents has not been produced. This study examines recent research trends in medical education for residents in radiation oncology through a scoping review. METHODS: We conducted a scoping review of medical education research for residents in radiation oncology to survey the research trends. We used publications available on MEDLINE, PubMed, and Scopus to conduct this scoping review. RESULTS: We screened 221 full-text articles, 146 of which met our inclusion criteria. These publications showed increased activity in medical education research for residents, most involving affiliations in the United States. We identified persistent interest in training-, contouring-, and technology-related issues. An increase in research related to career, treatment quality, and multidisciplinary training was also observed. However, no research about teacher training was identified. CONCLUSIONS: This scoping review presents the trends in study interests among stakeholders of medical education research in radiation oncology. With an investigation of existing studies, this research identifies areas of high priority and a lack of studies about teacher training. This study provides potential future directions for medical education research for residents in radiation oncology.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

Prognostic signature associated with radioresistance in head and neck cancer via transcriptomic and bioinformatic analyses.

BACKGROUND: Radiotherapy is an indispensable treatment modality in head and neck cancer (HNC), while radioresistance is the major cause of treatment failure. The aim of this study is to identify a prognostic molecular signature associated with radio-resistance in HNC for further clinical applications. METHODS: Affymetrix cDNA microarrays were used to globally survey different transcriptomes between HNC cell lines and isogenic radioresistant sublines. The KEGG and Partek bioinformatic analytical methods were used to assess functional pathways associated with radioresistance. The SurvExpress web tool was applied to study the clinical association between gene expression profiles and patient survival using The Cancer Genome Atlas (TCGA)-head and neck squamous cell carcinoma (HNSCC) dataset (n = 283). The Kaplan-Meier survival analyses were further validated after retrieving clinical data from the TCGA-HNSCC dataset (n = 502) via the Genomic Data Commons (GDC)-Data-Portal of National Cancer Institute. A panel maker molecule was generated to assess the efficacy of prognostic prediction for radiotherapy in HNC patients. RESULTS: In total, the expression of 255 molecules was found to be significantly altered in the radioresistant cell sublines, with 155 molecules up-regulated 100 down-regulated. Four core functional pathways were identified to enrich the up-regulated genes and were significantly associated with a worse prognosis in HNC patients, as the modulation of cellular focal adhesion, the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, and the regulation of stem cell pluripotency. Total of 16 up-regulated genes in the 4 core pathways were defined, and 11 over-expressed molecules showed correlated with poor survival (TCGA-HNSCC dataset, n = 283). Among these, 4 molecules were independently validated as key molecules associated with poor survival in HNC patients receiving radiotherapy (TCGA-HNSCC dataset, n = 502), as IGF1R (p = 0.0454, HR = 1.43), LAMC2 (p = 0.0235, HR = 1.50), ITGB1 (p = 0.0336, HR = 1.46), and IL-6 (p = 0.0033, HR = 1.68). Furthermore, the combined use of these 4 markers product an excellent result to predict worse radiotherapeutic outcome in HNC (p < 0.0001, HR = 2.44). CONCLUSIONS: Four core functional pathways and 4 key molecular markers significantly contributed to radioresistance in HNC. These molecular signatures may be used as a predictive biomarker panel, which can be further applied in personalized radiotherapy or as radio-sensitizing targets to treat refractory HNC.

Comparison of Lactase Variant MCM6 -13910 C>T Testing and Self-report of Dairy Sensitivity in Patients With Irritable Bowel Syndrome.

GOALS: To evaluate agreement of MCM6-13910 with self-report of dairy sensitivity (DS) and lactose hydrogen methane breath test (LHMBT) results in subjects with irritable bowel syndrome (IBS). BACKGROUND: IBS is a functional gastrointestinal disorder with symptoms including abdominal pain, variable bowel habits, and bloating. Adult patients with lactose malabsorption may present with similar symptoms. Patients with lactose malabsorption have a lactase nonpersistent (LNP) phenotype. Recent studies found 2 single nucleotide polymorphisms associated with LNP: G/A-22018 and C/T-13910. STUDY: Genotyping the MCM6-13910 variant of LNP in 538 IBS patients and 317 controls (without IBS). Subjects completed questionnaires pertaining to gastrointestinal problems and dietary consumption, with charts abstracted. RESULTS: Self-reported DS was higher in IBS (45%) than controls (9.8%, odds ratio=6.46, P<0.001). The C/C-13910 genotype was similar in IBS cases and controls, 81 (15.1%) and 47 (14.8%). Among subjects reporting DS, 49 (18.0%) had the C/C genotype. Overall agreement between genotype and self-reported DS was 0.06 in IBS and 0.07 in controls. There were 20 subjects with LHMBT results; 3 had positive results, 17 were negative. LNP genotypes were found in all 3 of positive LHMBT results; 16 had negative LHMBT among the 17 who were lactase persistent. Agreement between C/C-13910 genotype and LHMBT was excellent with κ-statistic of 0.83 (0.50-1.00). CONCLUSIONS: In IBS patients, self-report of lactose intolerance are highly prevalent but are a poor indicator of underlying C/C-13910 genotype. LHMBT had excellent agreement with C/C-13910 genotype.

Correction to: Mixture deconvolution by massively parallel sequencing of microhaplotypes.

The original version of this article contained an author name error. In this article, Katrina Madella has been corrected to Katrina Maddela.

Mixture deconvolution by massively parallel sequencing of microhaplotypes.

Short tandem repeat polymorphisms (STRs) are the standard markers for forensic human identification. STRs are highly polymorphic loci analyzed using a direct PCR-to-CE (capillary electrophoresis) approach. However, STRs have limitations particularly when dealing with complex mixtures. These include slippage of the polymerase during amplification causing stutter fragments that can be indistinguishable from minor contributor alleles, preferential amplification of shorter alleles, and limited number of loci that can be effectively co-amplified with CE. Massively parallel sequencing (MPS), by enabling a higher level of multiplexing and actual sequencing of the DNA, provides forensic practitioners an increased power of discrimination offered by the sequence of STR alleles and access to new sequence-based markers. Microhaplotypes (i.e., microhaps or MHs) are emerging multi-allelic loci of two or more SNPs within < 300 bp that are highly polymorphic, have alleles all of the same length, and do not generate stutter fragments. The growing number of loci described in the literature along with initial mixture investigations supports the potential for microhaps to aid in mixture interpretation and the purpose of this study was to demonstrate that practically. A panel of 36 microhaplotypes, selected from a set of over 130 loci, was tested with the Ion S5™ MPS platform (Thermo Fisher Scientific) on single-source samples, synthetic two-to-six person mixtures at different concentrations/contributor ratios, and on crime scene-like samples. The panel was tested both in multiplex with STRs and SNPs and individually. The analysis of single-source samples showed that the allele coverage ratio across all loci was 0.88 ± 0.08 which is in line with the peak height ratio of STR alleles in CE. In mixture studies, results showed that the input DNA can be much higher than with conventional CE, without the risk of oversaturating the detection system, enabling an increased sensitivity for the minor contributor in imbalanced mixtures with abundant amounts of DNA. Furthermore, the absence of stutter fragments simplifies the interpretation. On casework-like samples, MPS of MHs enabled the detection of a higher number of alleles from minor donors than MPS and CE of STRs. These results demonstrated that MPS of microhaplotypes can complement STRs and enhance human identification practices when dealing with complex imbalanced mixtures.

Selecting microhaplotypes optimized for different purposes.

Massively parallel sequencing is transforming forensic work by allowing various useful forensic markers, such as STRPs and SNPs, to be multiplexed providing information on ancestry, individual and familial identification, phenotypes for eye/hair/skin pigmentation, and the deconvolution of mixtures. Microhaplotypes also become feasible with massively parallel sequencing, these are DNA segments (smaller than 300 nucleotides) that are selected to contain multiple SNPs unambiguously defining three or more haplotype alleles occurring at common frequencies. The physical extent of a microhaplotype can thus be covered by a single sequence read making these loci phase-known codominant genetic systems. Such microhaplotypes supply significantly more information than a single SNP can. Our efforts to develop useful sets of microhaplotypes have already identified 182 such loci that we have studied on a large number of human populations from around the world. We present various analyses on 83 populations in our ongoing study for a subset of the best microhaplotypes currently available illustrating their characteristics and potential utility for ancestry, identification, and mixture deconvolution.

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

PURPOSE: Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. METHODS: We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. RESULTS: PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. CONCLUSIONS: For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.