Data-driven hypothesis generation among inexperienced clinical researchers: A comparison of secondary data analyses with visualization (VIADS) and other tools.

Objectives: To compare how clinical researchers generate data-driven hypotheses with a visual interactive analytic tool (VIADS, a visual interactive analysis tool for filtering and summarizing large datasets coded with hierarchical terminologies) or other tools. Methods: We recruited clinical researchers and separated them into "experienced" and "inexperienced" groups. Participants were randomly assigned to a VIADS or control group within the groups. Each participant conducted a remote 2-hour study session for hypothesis generation with the same study facilitator on the same datasets by following a think-aloud protocol. Screen activities and audio were recorded, transcribed, coded, and analyzed. Hypotheses were evaluated by seven experts on their validity, significance, and feasibility. We conducted multilevel random effect modeling for statistical tests. Results: Eighteen participants generated 227 hypotheses, of which 147 (65%) were valid. The VIADS and control groups generated a similar number of hypotheses. The VIADS group took a significantly shorter time to generate one hypothesis (e.g., among inexperienced clinical researchers, 258 s versus 379 s, p = 0.046, power = 0.437, ICC = 0.15). The VIADS group received significantly lower ratings than the control group on feasibility and the combination rating of validity, significance, and feasibility. Conclusion: The role of VIADS in hypothesis generation seems inconclusive. The VIADS group took a significantly shorter time to generate each hypothesis. However, the combined validity, significance, and feasibility ratings of their hypotheses were significantly lower. Further characterization of hypotheses, including specifics on how they might be improved, could guide future tool development.

How do clinical researchers generate data-driven scientific hypotheses? Cognitive events using think-aloud protocol.

Objectives: This study aims to identify the cognitive events related to information use (e.g., "Analyze data", "Seek connection") during hypothesis generation among clinical researchers. Specifically, we describe hypothesis generation using cognitive event counts and compare them between groups. Methods: The participants used the same datasets, followed the same scripts, used VIADS (a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies) or other analytical tools (as control) to analyze the datasets, and came up with hypotheses while following the think-aloud protocol. Their screen activities and audio were recorded and then transcribed and coded for cognitive events. Results: The VIADS group exhibited the lowest mean number of cognitive events per hypothesis and the smallest standard deviation. The experienced clinical researchers had approximately 10% more valid hypotheses than the inexperienced group. The VIADS users among the inexperienced clinical researchers exhibit a similar trend as the experienced clinical researchers in terms of the number of cognitive events and their respective percentages out of all the cognitive events. The highest percentages of cognitive events in hypothesis generation were "Using analysis results" (30%) and "Seeking connections" (23%). Conclusion: VIADS helped inexperienced clinical researchers use fewer cognitive events to generate hypotheses than the control group. This suggests that VIADS may guide participants to be more structured during hypothesis generation compared with the control group. The results provide evidence to explain the shorter average time needed by the VIADS group in generating each hypothesis.

Data-driven hypothesis generation among inexperienced clinical researchers: A comparison of secondary data analyses with visualization (VIADS) and other tools.

Objectives: To compare how clinical researchers generate data-driven hypotheses with a visual interactive analytic tool (VIADS, a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies) or other tools. Methods: We recruited clinical researchers and separated them into "experienced" and "inexperienced" groups. Participants were randomly assigned to a VIADS or control group within the groups. Each participant conducted a remote 2-hour study session for hypothesis generation with the same study facilitator on the same datasets by following a think-aloud protocol. Screen activities and audio were recorded, transcribed, coded, and analyzed. Hypotheses were evaluated by seven experts on their validity, significance, and feasibility. We conducted multilevel random effect modeling for statistical tests. Results: Eighteen participants generated 227 hypotheses, of which 147 (65%) were valid. The VIADS and control groups generated a similar number of hypotheses. The VIADS group took a significantly shorter time to generate one hypothesis (e.g., among inexperienced clinical researchers, 258 seconds versus 379 seconds, p = 0.046, power = 0.437, ICC = 0.15). The VIADS group received significantly lower ratings than the control group on feasibility and the combination rating of validity, significance, and feasibility. Conclusion: The role of VIADS in hypothesis generation seems inconclusive. The VIADS group took a significantly shorter time to generate each hypothesis. However, the combined validity, significance, and feasibility ratings of their hypotheses were significantly lower. Further characterization of hypotheses, including specifics on how they might be improved, could guide future tool development.

The effects of a gamified online course on pre-service teachers' confidence, intention, and motivation in integrating technology into teaching.

Teachers are gatekeepers of technology integration in the classroom. Pre-service teachers' attitudes, confidence, and competence in exploring emerging technologies play a critical role in teachers' adoption of technology in teaching. This study examined the effects of a gamified technology course on pre-service teachers' confidence, intention, and motivation in integrating technology into teaching. A sample of pre-service teachers (N = 84) at a Midwestern university in the United States in the academic year of 2021-22 was surveyed. The regression results revealed that the gamified course significantly and positively influenced pre-service teachers' confidence in using technology in education, intention to adopt gamification, and motivation to explore more emerging technologies for teaching, after controlling for gender. In contrast, gender did not affect pre-service teachers' confidence, intention, and motivation in integrating technology into instruction after controlling for the gamified course effects. Suggestions on gamifying course design while leveraging quest-based learning and active learning principles to enhance student positive attitudes and motivation to explore technology integration are discussed.

A Visual Analytic Tool (VIADS) to Assist the Hypothesis Generation Process in Clinical Research: Mixed Methods Usability Study.

BACKGROUND: Visualization can be a powerful tool to comprehend data sets, especially when they can be represented via hierarchical structures. Enhanced comprehension can facilitate the development of scientific hypotheses. However, the inclusion of excessive data can make visualizations overwhelming. OBJECTIVE: We developed a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS). In this study, we evaluated the usability of VIADS for visualizing data sets of patient diagnoses and procedures coded in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). METHODS: We used mixed methods in the study. A group of 12 clinical researchers participated in the generation of data-driven hypotheses using the same data sets and time frame (a 1-hour training session and a 2-hour study session) utilizing VIADS via the think-aloud protocol. The audio and screen activities were recorded remotely. A modified version of the System Usability Scale (SUS) survey and a brief survey with open-ended questions were administered after the study to assess the usability of VIADS and verify their intense usage experience with VIADS. RESULTS: The range of SUS scores was 37.5 to 87.5. The mean SUS score for VIADS was 71.88 (out of a possible 100, SD 14.62), and the median SUS was 75. The participants unanimously agreed that VIADS offers new perspectives on data sets (12/12, 100%), while 75% (8/12) agreed that VIADS facilitates understanding, presentation, and interpretation of underlying data sets. The comments on the utility of VIADS were positive and aligned well with the design objectives of VIADS. The answers to the open-ended questions in the modified SUS provided specific suggestions regarding potential improvements for VIADS, and the identified problems with usability were used to update the tool. CONCLUSIONS: This usability study demonstrates that VIADS is a usable tool for analyzing secondary data sets with good average usability, good SUS score, and favorable utility. Currently, VIADS accepts data sets with hierarchical codes and their corresponding frequencies. Consequently, only specific types of use cases are supported by the analytical results. Participants agreed, however, that VIADS provides new perspectives on data sets and is relatively easy to use. The VIADS functionalities most appreciated by participants were the ability to filter, summarize, compare, and visualize data. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/39414.

Development, validation, and usage of metrics to evaluate the quality of clinical research hypotheses.

Objectives: Metrics and instruments can provide guidance for clinical researchers to assess their potential research projects at an early stage before significant investment. Furthermore, metrics can also provide structured criteria for peer reviewers to assess others' clinical research manuscripts or grant proposals. This study aimed to develop, test, validate, and use evaluation metrics and instruments to accurately, consistently, and conveniently assess the quality of scientific hypotheses for clinical research projects. Materials and Methods: Metrics development went through iterative stages, including literature review, metrics and instrument development, internal and external testing and validation, and continuous revisions in each stage based on feedback. Furthermore, two experiments were conducted to determine brief and comprehensive versions of the instrument. Results: The brief version of the instrument contained three dimensions: validity, significance, and feasibility. The comprehensive version of metrics included novelty, clinical relevance, potential benefits and risks, ethicality, testability, clarity, interestingness, and the three dimensions of the brief version. Each evaluation dimension included 2 to 5 subitems to evaluate the specific aspects of each dimension. For example, validity included clinical validity and scientific validity. The brief and comprehensive versions of the instruments included 12 and 39 subitems, respectively. Each subitem used a 5-point Likert scale. Conclusion: The validated brief and comprehensive versions of metrics can provide standardized, consistent, and generic measurements for clinical research hypotheses, allow clinical researchers to prioritize their research ideas systematically, objectively, and consistently, and can be used as a tool for quality assessment during the peer review process.

[Mechanism of Xiaoluanwan(II) in treating mouse epididymitis through the regulation of NLRP3 inflammasome].

OBJECTIVE: This study aimed to investigate the mechanism of Xiaoluanwan(II) in treating lipopolysaccharide(LPS)-induced epididymitis and its impact on the NLRP3 inflammasome. METHODS: The murine epididymitis model was established through local injection of LPS. The study included a control group (n=5), a model group (n=5), a model group treated with Xiaoluanwan(II) (Ⅱ) (n=5), and a saline group treated with Xiaoluanwan(II) (n=5). After 14 consecutive days of oral administration of Xiaoluanwan(II) or physiological saline, pathological changes in the epididymal tissues, expression levels of NLRP3 inflammasome and Caspase-1, as well as associated protein levels were examined. RESULTS: Compared to the model group, Xiaoluanwan(II) significantly alleviated inflammatory cell infiltration and lesions, as evidenced by a reduction in the protein expression levels of NLRP3, Caspase-1, Cleaved-Caspase-1, IL-1ß, IL-18, GSDMD, and p-p38 MAPK (P<0.05 or P<0.01), thereby mitigating the inflammatory response. CONCLUSION: Xiaoluanwan(II) alleviates epididymal inflammation and ameliorates mouse epididymal epithelial injury by modulating the NLRP3-mediated cell pyroptosis pathway.

[Clinical observation of Xiaoluowan (II) in treating epididymitis].

OBJECTIVE: To observe the clinical efficacy of Xiaoluowan (II) on epididymitis. METHODS: 61 patients with epididymitis were divided into two groups, acute group (23 cases) and non-acute group (38 cases) . Both groups of patients were treated with Xiaoluowan (II) 6g twice a day orally, while acute group patients were given antibiotics intravenously. The treatment period is 4 weeks. The acute group evaluates the therapeutic efficacy comprehensively based on changes in clinical symptoms and signs, while recording changes in visual pain score (VAS). Chronic epididymitis symptom index (CESI) was used to evaluate the clinical symptoms before and after treatment in the non-acute group, and the curative efficacy was evaluated. RESULTS: After treatment, the VAS scores in the acute group decreased from 7.08 ± 1.09 to 2.10 ± 1.37 (P<0.05). Total efficiency is 82.60% . In the non-acute group, the scores of pain before and after treatment were 7.08 ± 1.09 and 2.10 ± 1.37, the scores of quality of life were 7.28 ± 1.14 and 1.87 ± 1.56, the total scores were 14.37 ± 1.78 and 3.97±2.73, respectively. The difference was significant(P<0.05). Total efficiency is 84.21% . CONCLUSION: Xiaoluowan (II) is an effective method to treat epididymitis and an effective supplement to modern medicine.

The Roles of a Secondary Data Analytics Tool and Experience in Scientific Hypothesis Generation in Clinical Research: Protocol for a Mixed Methods Study.

BACKGROUND: Scientific hypothesis generation is a critical step in scientific research that determines the direction and impact of any investigation. Despite its vital role, we have limited knowledge of the process itself, thus hindering our ability to address some critical questions. OBJECTIVE: This study aims to answer the following questions: To what extent can secondary data analytics tools facilitate the generation of scientific hypotheses during clinical research? Are the processes similar in developing clinical diagnoses during clinical practice and developing scientific hypotheses for clinical research projects? Furthermore, this study explores the process of scientific hypothesis generation in the context of clinical research. It was designed to compare the role of VIADS, a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies, and the experience levels of study participants during the scientific hypothesis generation process. METHODS: This manuscript introduces a study design. Experienced and inexperienced clinical researchers are being recruited since July 2021 to take part in this 2×2 factorial study, in which all participants use the same data sets during scientific hypothesis-generation sessions and follow predetermined scripts. The clinical researchers are separated into experienced or inexperienced groups based on predetermined criteria and are then randomly assigned into groups that use and do not use VIADS via block randomization. The study sessions, screen activities, and audio recordings of participants are captured. Participants use the think-aloud protocol during the study sessions. After each study session, every participant is given a follow-up survey, with participants using VIADS completing an additional modified System Usability Scale survey. A panel of clinical research experts will assess the scientific hypotheses generated by participants based on predeveloped metrics. All data will be anonymized, transcribed, aggregated, and analyzed. RESULTS: Data collection for this study began in July 2021. Recruitment uses a brief online survey. The preliminary results showed that study participants can generate a few to over a dozen scientific hypotheses during a 2-hour study session, regardless of whether they used VIADS or other analytics tools. A metric to more accurately, comprehensively, and consistently assess scientific hypotheses within a clinical research context has been developed. CONCLUSIONS: The scientific hypothesis-generation process is an advanced cognitive activity and a complex process. Our results so far show that clinical researchers can quickly generate initial scientific hypotheses based on data sets and prior experience. However, refining these scientific hypotheses is a much more time-consuming activity. To uncover the fundamental mechanisms underlying the generation of scientific hypotheses, we need breakthroughs that can capture thinking processes more precisely. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39414.

Health Indicators as Measures of Individual Health Status and Their Public Perspectives: Cross-sectional Survey Study.

BACKGROUND: Disease status (eg, cancer stage) has been used in routine clinical practice to determine more accurate treatment plans. Health-related indicators, such as mortality, morbidity, and population group life expectancy, have also been used. However, few studies have specifically focused on the comprehensive and objective measures of individual health status. OBJECTIVE: The aim of this study was to analyze the perspectives of the public toward 29 health indicators obtained from a literature review to provide evidence for further prioritization of the indicators. The difference between health status and disease status should be considered. METHODS: This study used a cross-sectional design. Online surveys were administered through Ohio University, ResearchMatch, and Clemson University, resulting in three samples. Participants aged 18 years or older rated the importance of the 29 health indicators. The rating results were aggregated and analyzed as follows (in each case, the dependent variables were the individual survey responses): (1) to determine the agreement among the three samples regarding the importance of each indicator, where the independent variables (IVs) were the three samples; (2) to examine the mean differences between the retained indicators with agreement across the three samples, where the IVs were the identified indicators; and (3) to rank the groups of indicators into various levels after grouping the indicators with no mean differences, where the IVs were the groups of indicators. RESULTS: In total, 1153 valid responses were analyzed. Descriptive statistics revealed that the top five-rated indicators were drug or substance abuse, smoking or tobacco use, alcohol abuse, major depression, and diet and nutrition. Among the 29 health indicators, the three samples agreed upon the importance of 13 indicators. Inferential statistical analysis indicated that some of the 13 indicators held equal importance. Therefore, the 13 indicators were categorized by rank into seven levels: level 1 included blood sugar level and immunization and vaccination; level 2 included LDL cholesterol; level 3 included HDL cholesterol, blood triglycerides, cancer screening detection, and total cholesterol; level 4 included health literacy rate; level 5 included personal care needs and air quality index greater than 100; level 6 included self-rated health status and HIV testing; and level 7 included the supply of dentists. Levels 1 to 3 were rated significantly higher than levels 4 to 7. CONCLUSIONS: This study provides a baseline for prioritizing 29 health indicators, which can be used by electronic health record or personal health record system designers or developers to determine what can be included in the systems to capture an individual's health status. Currently, self-rated health status is the predominantly used health indicator. Additionally, this study provides a foundation for tracking and measuring preventive health care services more accurately and for developing an individual health status index.

[Influence of the germline microbiome on male health and related diseases].

The reproductive microbiota plays an important role in male health and the development and progression of related diseases, but few studies have been reported on its action mechanism and future application. Microbiotas exist in different parts of the male reproductive system, as in the prostate, testicles and semen, with specific microbial characteristics. They are different in structure, bacterial abundance and dominant bacterial genera, and meanwhile closely related because of the relationship between the male reproductive and urinary systems in anatomy and function. The microbiota in the male reproductive system plays an essential role in maintaining the general and local homeostasis of the human genitourinary system. Imbalance of microbiotas can lead to the development and progression of related diseases. An insight into the action mechanism of microbiotas may contribute to the discovery of diagnostic biomarkers and new therapeutic targets for male diseases. This review summarizes the effects of reproductive microbiotas on male health and related diseases in order to help solve relevant clinical problems.

[Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele].

OBJECTIVE: To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC). METHODS: Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters. RESULTS: Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (ï¼»21.62 ± 9.25ï¼½ vs ï¼»28.88 ± 12.92ï¼½ ×106/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (ï¼»98.33 ± 0.15ï¼½% vs ï¼»96.27 ± 0.18ï¼½%, P < 0.05) and DNA fragmentation index (ï¼»19.72 ± 3.17ï¼½% vs ï¼»10.96 ± 3.82ï¼½%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types. CONCLUSIONS: Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

[Jujing Gouju Granules promote reproductive function in rats with spermatozoa].

OBJECTIVE: To observe the intervention effect of Jujing Gouju Granules (JGG) on teratozoospermia (TZ) in rats and explore its action mechanism. METHODS: Thirty-two male SD rats were randomly divided into four groups of an equal number: normal control, TZ model control, high-dose JGG and low-dose JGG. The TZ model was established in the latter three groups of rats by intragastric administration of methyl methanesulfonate at 4 mg/100 g body weight/day for 7 consecutive days. After successful modeling, the animals in the high- and low-dose JGG groups were treated with JGG at 0.288 and 0.072g/100 g body weight/d, respectively, while the normal controls with the same dose of normal saline, all for 48 days. At two days after medication, all the rats were sacrificed and the right epididymides harvested for sperm counting, sperm motility analysis, observation the sperm morphology, and determination of contents of fructose, zinc, α-glucosidase and superoxide dismutase (SOD) in the epididymal suspension, the levels of IL-6, IL-8 and TNF-α in the seminal plasma, and that of reactive oxygen species (ROS) in the sperm. RESULTS: Both sperm concentration and motility were significantly increased and the percentage of morphologically abnormal sperm decreased in the JGG groups compared with the model controls, even more significantly in the high- than in the low-dose JGG group (P < 0.05). No statistically significant difference was found in the contents of fructose and zinc in the epididymal suspension among the four groups, but that of α-glucosidase was remarkably lower in the TZ model than in the normal controls (ï¼»50.31 ± 2.12ï¼½ vs ï¼»67.23 ± 3.54ï¼½ U/L, P < 0.05), but higher in the high- and low-dose JGG groups (ï¼»79.36 ± 2.35ï¼½ and ï¼»56.25 ± 3.44ï¼½ U/L) than in the model control group (P < 0.05). The level of ROS was markedly higher and that of SOD lower in the TZ model than in the normal controls, while the former was lower and the latter was higher in the JGG groups than in the TZ model controls (P < 0.05), even more significantly in the in the high- than in the low-dose JGG group (P < 0.05). Compared with the TZ model controls, the rats in the JGG groups showed dramatically decreased levels of IL-6, IL-8 and TNF-α in the seminal plasma, even more significantly in the high- than in the low-dose JGG group (P < 0.05). CONCLUSIONS: Jujing Gouju Granules can improve sperm morphology in teratozoospermia rats, possibly by regulating oxidative stress and inflammation-related factors.

[Genetic analysis of a child with mental retardation and hypospadia].

OBJECTIVE: To carry out genetic testing for a boy presenting with mental retardation and hypoplasia. METHODS: Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents. RESULTS: SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46,XX,ish ins(11;2) (p15;q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46,XY,ish der(11)ins(11;2) (p15;q33q36)mat. CONCLUSION: SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.

A visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS).

BACKGROUND: Vast volumes of data, coded through hierarchical terminologies (e.g., International Classification of Diseases, Tenth Revision-Clinical Modification [ICD10-CM], Medical Subject Headings [MeSH]), are generated routinely in electronic health record systems and medical literature databases. Although graphic representations can help to augment human understanding of such data sets, a graph with hundreds or thousands of nodes challenges human comprehension. To improve comprehension, new tools are needed to extract the overviews of such data sets. We aim to develop a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS) as an online, and publicly accessible tool. The ultimate goals are to filter, summarize the health data sets, extract insights, compare and highlight the differences between various health data sets by using VIADS. The results generated from VIADS can be utilized as data-driven evidence to facilitate clinicians, clinical researchers, and health care administrators to make more informed clinical, research, and administrative decisions. We utilized the following tools and the development environments to develop VIADS: Django, Python, JavaScript, Vis.js, Graph.js, JQuery, Plotly, Chart.js, Unittest, R, and MySQL. RESULTS: VIADS was developed successfully and the beta version is accessible publicly. In this paper, we introduce the architecture design, development, and functionalities of VIADS. VIADS includes six modules: user account management module, data sets validation module, data analytic module, data visualization module, terminology module, dashboard. Currently, VIADS supports health data sets coded by ICD-9, ICD-10, and MeSH. We also present the visualization improvement provided by VIADS in regard to interactive features (e.g., zoom in and out, customization of graph layout, expanded information of nodes, 3D plots) and efficient screen space usage. CONCLUSIONS: VIADS meets the design objectives and can be used to filter, summarize, compare, highlight and visualize large health data sets that coded by hierarchical terminologies, such as ICD-9, ICD-10 and MeSH. Our further usability and utility studies will provide more details about how the end users are using VIADS to facilitate their clinical, research or health administrative decision making.

[Application of single nucleotide polymorphism array for the identification of pathogenic copy number variations in fetuses with malformations and women with an adverse reproductive history].

OBJECTIVE: To apply single nucleotide polymorphism microarray (SNP array) for the detection of genome-wide copy number variations(CNVs) in fetuses with malformations and women with an adverse reproductive history, and to explore the correlation of rare CNVs with the clinical manifestations. METHODS: Amniotic fluid and umbilical cord blood samples were collected from 314 women with singleton pregnancy. SNP array was performed on samples where chromosomal abnormalities were excluded after G-banding analysis. RESULTS: Pathological CNVs were detected in 8.91% (28/314) of all samples, which included 11 duplications, 9 deletions, 4 loss of heterozygosity (LOH), and 4 conjoined deletions and duplications. The sizes of duplications and deletions were between 0.47 Mb and 16.7 Mb, and between 0.16 Mb and 13.3 Mb, respectively. Fifteen CNVs were mapped to the regions of microdeletion or microduplication syndromes or regions associated with clinical manifestations, while the remainder 13 were considered benign or variant of uncertain significance. CONCLUSION: A proportion of fetuses with malformations and women with an adverse reproductive history may be attributed to CNVs, half of which are mapped with to the regions of well known syndromes. SNP array may facilitate discovery of new syndromes and provide a basis for genetic counseling and prenatal diagnosis.

A de novo duplication of chromosome 9q34.13-qter in a fetus with Tetralogy of Fallot Syndrome.

BACKGROUND: Partial duplications of the distal 9q have been rarely reported in literatures. The key features included characteristic facial appearance, long fingers and toes, slight psychomotor retardation, heart murmur et al. But rare severe congenital heart defects (CHD) such as TOF were reported to be associated with 9qter duplications. CASE PRESENTATION: A 23-year-old woman was referred for genetic counseling and prenatal diagnosis at 25(3/7) weeks of gestation due to her male fetus, diagnosed as Tetralogy of Fallot Syndrome (TOF) by prenatal ultrasound. SNP (Single nucleotide polymorphism) array revealed that the male fetus had a de novo 5.47 Mb duplication at 9q34.13-qter. Meanwhile, non-invasive prenatal testing (NIPT) using low coverage whole genome massively parallel sequencing of circulating cell-free fetal DNA (cffDNA) showed consistent results. Multiplex ligation-dependent probe amplification (MLPA) also confirmed the duplication at 9qter. CONCLUSION: In this paper, we present an Asian fetus with TOF caused by a de novo 5.47 Mb duplication at 9q34.13-qter. Duplication of 9q34.13-qter should be considered as an etiological diagnosis in the case of TOF. Our prenatal diagnostic findings provide important information for genetic counseling on the male fetus and future pregnancies in this family. Chromosomal microarray analysis (CMA) remains the first-tier clinical diagnostic test for prenatal fetus with suspicious syndromes. We also highlight the high potential application of NIPT in the screening of sub-chromosomal rearrangement.

The Breed and Sex Effect on the Carcass Size Performance and Meat Quality of Yak in Different Muscles.

The carcass size performances and the meat quality of Gannan and Sibu yak were determined using M. supraspinatus (SU), M. longissimus thoracis (LT) and M.quadriceps femoris (QF). It is found that Sibu yak had significantly higher carcass weight (CW) than Gannan yak with difference of nearly 40 kg, as well as significantly higher eye muscle area (EMA), carcass thorax depth (CTD), round perimeter (RP), etc. The carcass performances of steer yak were significantly higher than heifer yak except meat thickness at round (MTR) (p<0.05). The results show that both yak breed and gender had significant effects on carcass performances. It could be seen that the variation of carcass size performances from breeds is as large as from gender (50.22% and 46.25% of total variation, respectively) through principal component analysis (PCA). Sibu yak had significantly higher L*, b*, WBSF, cooking loss and Fat content, while Gannan yak had significantly higher a*, press loss, protein content and moisture (p<0.05). Yak gender and muscle had insignificant effects on meat colour and water holding capacity (p>0.05). The variation of meat quality of yak from breed is up to 59.46% of total variation according to PCA. It is shown that the difference between breeds, for Gannan yak and Sibu yak, plays an important role in carcass size performance and meat quality.

[Immune mechanisms of the active ingredients of Chinese medicinal herbs for chronic prostatitis].

Chronic prostatitis is a common male disease, and its pathogenesis is not yet clear. Most scholars believe that oxidative stress and immune imbalance are the keys to the occurrence and progression of chronic prostatitis. Currently immunotherapy of chronic prostatitis remains in the exploratory stage. This article relates the active ingredients of 5 Chinese medicinal herbs (total glucosides of paeony, tripterigium wilfordii polglycosidium, curcumin, geniposide, and quercetin) for the treatment of chronic prostatitis and their possible action mechanisms as follows: 1) inhibiting the immune response and activation and proliferation of T-cells, and adjusting the proportion of Th1/Th2 cells; 2) upregulating the expression of Treg and enhancing the patient's tolerability; 3) suppressing the activation of the NF-kB factor, reducing the release of iNOS, and further decreasing the release of NO, IL-2 and other inflammatory cytokines, which contribute to the suppression of the immune response; 4) inhibiting the production of such chemokines as MCP-1 and MIP-1α in order to reduce their induction of inflammatory response. Studies on the immune mechanisms of Chinese medicinal herbs in the treatment of chronic prostatitis are clinically valuable for the development of new drugs for this disease.

Marital Hostility, Hostile Parenting, and Child Aggression: Associations from Toddlerhood to School Age.

OBJECTIVE: The spillover hypothesis suggests that childhood aggression results from spillover of interparental conflict to poor parenting, which promotes aggressive child behavior. This study was designed to examine the spillover hypothesis in non-genetically related parent-child dyads from the toddler period through age 6 years. METHOD: A sample of 361 sets of children, adoptive parents, and birth parents from the Early Growth and Development Study (EGDS) was assessed from child age 9 months to 6 years on measures of adoptive parent financial strain, antisocial traits, marital hostility, hostile parenting, and child aggression. Structural equation modeling was used to examine links from financial strain, parent antisocial traits, and marital hostility in infancy and toddlerhood to hostile parenting and child aggression at ages 4.5 and 6 years. RESULTS: Spillover of marital conflict from child age 18 to 27 months was associated with more parental hostility in mothers and fathers at 27 months. In turn, adoptive fathers' parental hostility, but not mothers', was associated with aggression in children at age 4.5 years. However, there was no significant spillover from hostile parenting at 4.5 years to child aggression at 6 years. Birth mother antisocial traits were unassociated with child aggression. CONCLUSION: This study is the first to examine spillover of marital hostility to parenting to child aggression from toddlerhood through age 6 years in an adoption design, highlighting the impact of these environmental factors from the toddler to preschool period. The findings support the potential benefit of early identification of marital hostility.