Evaluation of large-scale highly polymorphic microhaplotypes in complex DNA mixtures analysis using RMNE method.

DNA mixture interpretation is one of the most challenging problems in forensics. Complex DNA mixtures are more difficult to analyze when there are more than two contributors or related contributors. Microhaplotypes (MHs) are polymorphic genetic markers recently discovered and employed in DNA mixture analysis. However, the evidentiary interpretation of the MH genotyping data needs more debate. The Random Man Not Excluded (RMNE) method analyzes DNA mixtures without using allelic peak height data or the number of contributors (NoC) assumptions. This study aimed to assess how well RMNE interpreted mixed MH genotyping data. We classified the MH loci from the 1000 Genomes Project database into groups based on their Ae values. Then we performed simulations of DNA mixtures with 2-10 unrelated contributors and DNA mixtures with a pair of sibling contributors. For each simulated DNA mixture, incorrectly included ratios were estimated for three types of non-contributors: random men, parents of contributors, and siblings of contributors. Meanwhile, RMNE probability was calculated for contributors and three types of non-contributors, allowing loci mismatch. The results showed that the MH number, the MH Ae values, and the NoC affected the RMNE probability of the mixture and the incorrectly included ratio of non-contributors. When there were more MHs, MHs with higher Ae values, and a mixture with less NoC, the RMNE probability, and the incorrectly included ratio decreased. The existence of kinship in mixtures complicated the mixture interpretation. Contributors' relatives as non-contributors and related contributors in the mixture increased the demands on the genetic markers to identify the contributors correctly. When 500 highly polymorphic MHs with Ae values higher than 5 were used, the four individual types could be distinguished according to the RMNE probabilities. This study reveals the promising potential of MH as a genetic marker for mixed DNA interpretation and the broadening of RMNE as a parameter indicating the relationship of a specific individual with a DNA mixture in the DNA database search.

RECIST 1.1 versus mRECIST for assessment of tumour response to molecular targeted therapies and disease outcomes in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVES: Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS). DESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021. ELIGIBILITY CRITERIA: We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis. RESULTS: 23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p<0.001). The DCR is similar (68.4% vs 67.2%, p=0.5). The agreement of tumour response is moderate for objective response (k=0.499) and perfect for progressive disease (k=0.901), calculated from 8 studies including 372 patients. OS was significantly longer in response group than non-response group according to mRECIST (HR 0.56, 95% CI 0.41 to 0.78, p=0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted. CONCLUSIONS: mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical. PROSPERO REGISTRATION NUMBER: CRD42020200895. ETHICS APPROVAL: Ethics approval is not required in this meta-analysis.

The Empirical Investigation Between Ethical Leadership and Knowledge-Hiding Behavior in Financial Service Sector: A Moderated-Mediated Model.

This study aimed to investigate the impact of ethical leadership on knowledge-hiding behavior of the employees working in the financial services sector under the mediating role of meaningful at work and moderating role of ethical climate. For this purpose, data were collected from two hundred and fifteen employees of financial services providing organizations. The already-established scales were followed to develop an instrument that was used to obtain responses from the respondents. Collected data were analyzed by applying the structural equation modeling through Smart PLS and Process Macro. The results indicate that ethical leadership and meaningful work (MW) reduce knowledge-hiding behavior of employees at work, while ethical leadership positively impacts the influential work of employees at the workplace. Further, the relationship between ethical leadership and knowledge-hiding behavior is partially mediated by MW. Similarly, ethical climate moderated the relationship between ethical leadership and knowledge-hiding behavior. This research makes valuable contributions to the existing literature on leadership and knowledge management. From a practical point of view, this study stresses that managers at work should promote ethical leadership styles to promote MW, which will reduce knowledge hiding. Thus, in this way, it will enhance the innovation and creativity within organizational circuits. The limitations and future directions of this study are also listed.

A Two-Ended Data-Driven Accelerated Sampling Method for Exploring the Transition Pathways between Two Known States of Protein.

Conformational transitions of protein between different states are often associated with their biological functions. These dynamic processes, however, are usually not easy to be well characterized by experimental measurements, mainly because of inadequate temporal and spatial resolution. Meantime, sampling of configuration space with molecular dynamics (MD) simulations is still a challenge. Here we proposed a robust two-ended data-driven accelerated (teDA2) conformational sampling method, which drives the structural change in an adaptively updated feature space without introducing a bias potential. teDA2 was applied to explore adenylate kinase (ADK), a model with well characterized "open" and "closed" states. A single conformational transition event of ADK could be achieved within only a few or tens of nanoseconds sampled with teDA2. By analyzing hundreds of transition events, we reproduced different mechanisms and the associated pathways for domain motion of ADK reported in the literature. The multiroute characteristic of ADK was confirmed by the fact that some metastable states identified with teDA2 resemble available crystal structures determined at different conditions. This feature was further validated with Markov state modeling with independent MD simulations. Therefore, our work provides strong evidence for the conformational plasticity of protein, which is mainly due to the inherent degree of flexibility. As a reliable and efficient enhanced sampling protocol, teDA2 could be used to study the dynamics between functional states of various biomolecular machines.

The epidemiology of NAFLD in Mainland China with analysis by adjusted gross regional domestic product: a meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. This study aimed to estimate the prevalence, incidence, and outcome of NAFLD in the large and diverse population of Mainland China. METHODS: PubMed, Embase, and the Cochrane Library databases were searched to identify published studies with NAFLD epidemiology data in adult participants (≥ 18 years old) from Mainland China. Random effects models were used to determine pooled estimates. RESULTS: We screened 1,328 studies and included 167 eligible studies (participant n = 1,486,635): 149 studies (n = 1,350,819) for prevalence, 18 studies (n = 147,316) for incidence, 7 studies (n = 5446) for evolution of hepatic steatosis, and 2 studies (n = 647) for mortality analysis. The NAFLD prevalence of the overall populations was 29.88%, with higher rates in males, increasing age and increasing gross regional domestic product (GRDP) per capita (all p ≤ 0.010). The prevalence was the highest in North China (36.41%; higher in Uyghur and Hui Chinese 40.86% and 34.36% vs 28.11% in Han Chinese), higher in diabetics (51.83% vs. 30.76% in non-diabetics) and in obese participants (66.21% vs. 11.72% in lean). The NAFLD incidence was 56.7 (95% CI 47.4-66.8) per 1000 person-years, higher in males and with higher GRDP per capita. The overall mortality was 7.3 (3.3-12.7) per 1000 person-years. CONCLUSIONS: The overall prevalence of NAFLD in Mainland China is about 30%. The highest prevalences were found among regions with higher income, North China, the non-Han ethnic minorities, diabetics, and the obese. China's NAFLD prevalence is on par with Western countries.

Ultrasound strain imaging in assessment of false vocal folds in adults: A feasibility study.

PURPOSE: The aim of the study is to investigate the feasibility of ultrasound strain imaging (USI) in assessing magnitude and symmetry of false vocal folds (FVF) deformation as a quantitative marker for estimating FVF movement. METHODS: From October 2016 to July 2017, we performed USI of FVF in 44 adults [33 healthy controls and 11 subjects with unilateral vocal fold motion impairment (VFMI), 17 men and 27 women, mean age 43 years]. Real time ultrasound data of FVF in different configuration (abduction and adduction) was acquired through transcutaneous anterior-mid neck. Peak to valley strain (strain magnitude of maximum to minimum) representing the largest FVF deformation was estimated using 2-D speckle tracking. We developed peak to valley strain index [(Peak to valley strain right - Peak to valley strain left)/Peak to valley strain maximum] to assess the symmetry of FVF deformation. RESULTS: The difference in peak to valley strain between left and right FVF was significant in subjects with VFMI, whereas it was not in healthy controls. The peak to valley strain index was small (≤0.25) in symmetric FVF deformation in healthy controls whereas it was large (≥0.53) in asymmetric FVF deformation in subjects with VFMI. The area under receiver operating characteristics for peak to valley strain index in the determining asymmetric FVF deformation was 1. CONCLUSION: Our results suggest that USI seems feasible to quantify both magnitude and symmetry of FVF deformation in adults. Further validation of USI in assessing VFMI is warranted.

Ultrasonographic assessment of male breast diseases.

Although rare and accounting for less than 1% of all breast cancers, the incidence of breast cancer in men has increased by 26% over the past few decades. Very little has been reported on the sonographic appearance of benign and malignant male breast conditions. The aim of this study was to describe the ultrasonographic features of male breast disease and the value of ultrasound in the evaluation of male breast disease. Between December 2006 and October 2014, ultrasound examinations were performed in 560 male patients presenting with enlargement of, pain in, and/or a lump in the breast. One hundred and thirty-six patients (24.3%) underwent surgical excision, and 424 patients (75.7%) were diagnosed by ultrasound. Their ultrasonographic features were retrospectively evaluated. The final diagnoses were gynecomastia (n = 537), primary breast cancer (n = 9), lipoma (n = 7), chronic mastitis (n = 6), and fibroadenoma (n = 1). Of the 560 lesions, 356 (63.6%) were classified as Breast Imaging Reporting and Data System (BI-RADS) category 2, 191 (34.1%) were classified as BI-RADS category 3, and 13 (2.3%) were classified as BI-RADS 4 or 5. The sensitivity, specificity, PPV, NPV, and accuracy of the detection of malignant breast masses according to ultrasound were 100%, 99.3%, 69.2%, 100%, and 97.7% respectively. The sonographic patterns of gynecomastia were nodular (n = 131, 24.4%), dendritic (n = 50, 9.3%), and diffuse glandular (n = 356, 66.3%). Color Doppler flow imaging revealed hypervascularity in five of these malignant masses, moderate vascularity in two of the masses, and mild vascularity in the remaining two masses. Other diseases included in the study are also described. Ultrasonography (US) is useful in the diagnosis of male breast diseases, especially in differentiating cancer from benign lesions.

Sonographic assessment of hypopharyngeal carcinoma: preliminary study.

OBJECTIVES: This study investigated the ability of sonography for diagnosis of hypopharyngeal carcinoma. METHODS: Between November 2008 and January 2010, 34 consecutive patients with hypopharyngeal carcinoma (34 tumors) were examined by sonography. The visualization capability of sonography was evaluated by grading criteria of "excellent," "good," "moderate," and "poor" in comparison with computed tomography (CT). Localization of the primary tumor foci and intrahypopharyngeal and extrahypopharyngeal invasion were initially assessed by sonography and confirmed with surgical and pathologic findings. Laryngeal movement was observed on real-time sonography and compared with endoscopic findings. RESULTS: On sonography, 29 of the 34 lesions (85.3%) were graded excellent, similar to the shapes and dimensions of the tumors on CT. Localization was correctly undertaken in 26 of the 28 foci resected (92.9%), with excellent agreement between sonography and surgical and pathologic findings (κ = 0.823; P < .001). In evaluating intrahypopharyngeal and extrahypopharyngeal invasion with sonography, the sensitivity and specificity were 90.9% and 82.4%, respectively, for intrahypopharyngeal intersubsite spreading, 50.0% and 96.2% for diagnosis of thyroid cartilage destruction, both 100% for evaluation of cervical esophagus, neck soft tissue, and thyroid gland involvement, and 76.9% and 100% for assessment of hemilarynx fixation. CONCLUSIONS: Sonography has a similar role in visualization of hypopharyngeal carcinoma as CT and is satisfactory in localization of the primary focus and assessment of tumor extension inside and outside the hypopharynx.

[Quality assessment for Coptis chinensis with different cultivating system].

OBJECTIVE: To evaluate the quality of Coptis chinensis planted with four kinds of cultivating system. METHOD: The samples, which were planted below the artificial shading, the forest of Chinese ceder wood, Mmulbery wood, Magnolia officinal wood were chosen respectivley, UV and HPLC were used to determine of total alkaloids and berberine of samples. RESULT: There was no significant difference among four kinds of cultivating system on the contents of total alkaloids and berberine. The contents of total alkaloids and berberine were obviously higher than in the criterion of Chinese Pharmacopoeia. CONCLUSION: The roots of C. chinensis planted in the four kinds of planting system can be used as medicinal material of high quality.

Assessment of renal cell carcinoma after cryoablation using contrast-enhanced gray-scale ultrasound: a case series.

We performed contrast-enhanced gray-scale harmonic ultrasound (CUS) in three patients with renal cell carcinoma after cryoablation. CUS showed the decreased enhancement similar to the findings of CT or MRI. It identified feeding vessels more distinctly and found a larger number compared with CT or MRI. A persistent feeder in one case was related to recurrence. CUS may potentially be an alternative to CT and MRI and a useful method in the prediction of recurrent and residual tumors.