[Evaluation of the efficacy of GnRH-a pretreatment before total hysterectomy for adenomyosis patients: a propensity score matching analysis].

Objective: To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia. Methods: From January 2018 to March 2023, 689 patients who underwent total hysterectomy for adenomyosis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the preoperative medication, they were divided into study group (127 cases) and control group (562 cases). Patients in the study group underwent GnRH-a pretreatment for 3 cycles before surgery, and the control group received operation directly. SPSS 26.0 software was used to perform 1∶1 matching for the two groups of patients through the propensity score matching method. Matching variables included age, body mass index, gravidity, parity, history of pelvic and abdominal surgery, menstrual cycle, menstrual period, dysmenorrhea score, initial diagnosis of cancer antigen 125 (CA125), uterine volume and hemoglobin value. The dysmenorrhea score, uterine volume, hemoglobin value and CA125 level before and after GnRH-a pretreatment in the study group were compared. And the duration of operation, intraoperative blood loss, postoperative white blood cell count, perioperative blood transfusion cases, postoperative disease rate, duration of hospitalization, total hospitalization cost between the two groups were compared. Results: With propensity score matching, 119 patients in the study group and 119 patients in the control group were finally enrolled in this study. In the study group, before and after the treatment with GnRH-a, the dysmenorrhea score (7.4±1.7 vs 5.6±1.8), uterine volume [(362±160) vs (233±126) cm3], hemoglobin value [(74.1±10.7) vs (102.5±13.5) g/L], and CA125 level [(104±76) vs (64±51) kU/L] were statistically different (all P<0.05). There were statistical differences of operation time [(86±18) vs (116±31) minutes], intraoperative blood loss [(24±9) vs (43±22) ml], white blood cell count after 1 day of operation [(9.80±0.10)×109/L vs (9.90±0.10)×109/L], number of perioperative blood transfusion case [5.9% (7/119) vs 61.3% (73/119)], postoperative disease rate [5.0% (6/119) vs 16.0% (19/119)], hospitalization duration [(7.1±1.6) vs (7.9±1.6) days], and total hospitalization cost [(35 323±5 275) vs (37 159±5 640) yuan] between the study group and the control group (all P<0.05). Conclusion: The pretreatment of using GnRH-a before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia is not only conducive to improving dysmenorrhea, signs of anemia, reducing uterine volume, but also conducive to the implementation of surgery, reducing intraoperative and postoperative complications, and reducing hospital costs.

A preliminary study on the diversity of butyrate-producing bacteria in response to the treatment of depression with Xiaoyaosan.

Butyrate-producing bacteria generate butyrate, which has antidepressant effects. Xiaoyaosan (XYS), a traditional Chinese medicine (TCM) used to treat depression, may improve depression-like behaviour by modulating the gut microbiota. However, the functional groups and mechanisms of action in the XYS treatment of depression remain unknown. This study aimed to analyse with clone sequencing the changes in intestinal butyrate-producing bacteria in XYS-treated chronic unpredictable mild stress (CUMS) rats. We successfully established the XYS-treated CUMS rat model of depression. Rat faecal samples were collected before, during, and after the experiment, and butyryl-CoA:acetate CoA-transferase gene primers were selected for PCR amplification to determine the diversity of butyrate-producing bacteria. The results showed that XYS increased intestinal butyrate-producing bacterial diversity in CUMS rats regarding phylum and genus numbers; the number of phyla increased to two, distributed in Firmicutes and Bacteroides, and four genera were distributed in Eubacterium sp., Roseburia sp., Clostridium sp. and Bacteroides sp. Only one phylum and two genera were present in the model group without XYS treatment. Our findings indicate that XYS can improve depression-like behaviour by regulating intestinal butyrate-producing bacteria diversity, particularly Roseburia sp. and Eubacterium sp., thus providing new insights into the targeted regulation of the intestinal flora to treat depression.

[Prediction of platinum-based chemotherapy sensitivity for epithelial ovarian cancer by multi-sequence MRI-based radiomic nomogram].

Objective: To investigate a preoperative multi-sequence MRI-based radiomic nomogram for prediction of platinum-based chemotherapy sensitivity in patients with epithelial ovarian cancer (EOC). Methods: The complete data of 114 patients with EOC confirmed by surgery and pathology in Nantong Tumor Hospital of Nantong University from January 2015 to May 2020 were retrospectively analyzed, with an average age of 32-76 (57±8) years. All patients underwent platinum-based chemotherapy after maximal cytoreductive surgery. According to whether relapse occurred within 6 months, those patients were divided into platinum-resistant disease (PR, n=39) group and platinum-sensitive disease group (PS, n=75).All patients underwent MRI examination before treatment, and the 3-dimensional solid component of the tumor area of interest (ROI) on T2-weighted image (T2WI), diffusion weighted imaging (DWI) and T1-weighted image-enhanced image (T1CE) were manually delineated using Itk-snap software.Then AK software was imported for radiomics features extracting. They were randomly divided into training group (n=80) and validation group (n=34) in a ratio of 7∶3 (stratified sampling method). Firstly, the radiomics features were initially screened by the method of maximum correlation and minimum redundancy (mRMR), and features with the greatest predictive power were retained. Then, the LASSO regression analysis was performed to select the best features and construct the radiomics model. Univariate analysis was used to screen out clinical relevant factors, which combined with radiomic score (Radscore) was applied to develop a radiomics nomogram by multivariable logistic regression. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the predictive ability and clinical application value of radiomics model, clinical related factor model and radiomics nomogram. Results: Compared with the radiomics model (12 optimal radiomics features) and the clinical relevant factors model (residual disease, neutrophil count, carbohydrate antigen 199), the radiomics nomogram model demonstrated the best prediction performance: in the training groups, the AUC (Area Under the ROC Curve), accuracy, sensitivity, and specificity were 0.90 (95%CI:0.82-0.99), 90.0%, 89.0%, and 92.0%, respectively. In the validation groups, the AUC, accuracy, sensitivity, and specificity were 0.89 (95%CI:0.78-1.00), 85.0%, 87.0%, and 80.0%, respectively. DCA shows that the use of nomograms with a threshold in the range of 0.01 to 0.90 has a greater clinical application value in predicting the sensitivity of platinum chemotherapy in patients with EOC. Conclusion: The multi-sequence MRI-based radiomics nomogram has a high diagnostic value in predicting the sensitivity of platinum-based chemotherapy in patients with EOC.

Plis de passage in the superior temporal sulcus: Morphology and local connectivity.

While there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large individual variability. In particular, an accurate characterization of the "plis de passage" (PPs), annectant gyri inside the fold, is lacking to explain this variability. Performed on 90 subjects of the HCP database, our study revealed that PPs constitute landmarks that can be identified from the geometry of the STS walls. They were found associated with a specific U-shape white-matter connectivity between the two banks of the sulcus, the amount of connectivity being related to the depth of the PPs. These findings raise new hypotheses regarding the spatial organization of PPs, the relation between cortical anatomy and structural connectivity, as well as the possible role of PPs in the regional functional organization.

[Expression of VHL, VEGF and HIF-1α in endolymphatic sac tumors].

Objective: To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation. Methods: Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed. Results: The expression rate of VHL in the ELST group was significantly lower than that in the control group (P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group (P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage (P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST (P>0.05). Conclusions: The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.

[Association between root abnormalities and related pathogenic genes in patients with generalized aggressive periodontitis].

OBJECTIVE: To explore the association between the abnormal root morphology and bone metabolism or root development related gene polymorphism in patients with generalized aggressive periodontitis. METHODS: In the study, 179 patients with generalized aggressive periodontitis were enrolled, with an average age of (27.23±5.19) years, male / female = 67/112. The average number of teeth remaining in the mouth was (26.80±1.84). Thirteen single nucleotide polymorphisms (SNPs) of nine genes which related to bone metabolism and root development were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Root abnormalities were identified using periapical radiographs. The abnormal root morphology included cone-rooted teeth, slender-root teeth, short-rooted teeth, curved-rooted teeth, syncretic-rooted molars, and molar root abnormalities. The number of teeth and incidence of abnormal root morphology in different genotypes of 13 SNPs were analyzed. RESULTS: The constituent ratio of root with root abnormality in GAgP patients was 14.49%(695/4 798). The average number of teeth with abnormal root morphology in GAgP was (3.88±3.84). The average number of teeth with abnormal root morphology in CC, CT and TT genotypes in vitamin D receptor (VDR) rs2228570 was (4.66±4.10), (3.71±3.93) and (2.68±2.68). There was significant difference between TT genotype and CC genotype (t = 2.62, P =0.01). The average number of root morphological abnormalities in CC, CT and TT genotypes of Calcitotin Receptor (CTR) gene rs2283002 was (5.02±3.70), (3.43±3.95), and (3.05±3.12). The incidence of root morphological abnormalities in CC genotype was higher than that in the patients with CT and TT, and the difference was statistically significant(87.86% vs. 65.26% & 63.64%, P=0.006, adjusted OR =3.71, 95%CI: 1.45-9.50). There was no significant difference in the incidence of abnormal root morphology between CT and TT genotypes. CONCLUSION: VDR rs2228570 and CTR rs2283002 may be associated with the occurrence of abnormal root morphology in patients with generalized aggressive periodontitis, which is worthy of further research.

[Alveolar crest and relevant analysis of labial side of anterior teeth on skeletal Angle class III patients].

OBJECTIVE: To measure the distance from cemento-enamel junction (CEJ) to alveolar crest (AC) of labial side of anterior teeth on skeletal Angle class III patients under direct vision during periodontal bone augmentation surgery and to make relevant analysis to find the relevant factors. METHODS: In the study, 46 skeletal Angle class III patients (10 males and 36 females) received periodontal bone augmentation surgery of anterior teeth were included, with 67 jaws (27 maxillae and 40 mandibles) and 400 anterior teeth (161 maxillary anterior teeth and 239 mandibular anterior teeth). The mean age was 23.65 years. Maxillary anterior teeth consisted of 54 central incisors, 53 lateral incisors and 54 canines. Mandibular anterior teeth consisted of 79 central incisors, 80 lateral incisors and 80 canines. CEJ-AC was measured in three sites (mesial sites, central sites and distal sites) by Williams periodontal probes during periodontal bone augmentation surgery under direct vision by the same researcher. RESULTS: The average CEJ-AC of 400 anterior teeth was (2.21±1.48) mm. The average CEJ-AC of maxillary anterior teeth was (1.72±1.13) mm, more than (2.54±1.60) mm of mandibular anterior teeth (P<0.05). The average CEJ-AC of canines was (2.42±1.78) mm, more than (2.06±1.27) mm of central incisors or (2.16±1.32) mm of lateral incisors (P<0.05). The average CEJ-AC of central sites was (3.04±2.01) mm, more than (1.79±0.86) mm of mesial sites or (1.81±0.89) mm of distal sites (P<0.05). CEJ-AC of 233 anterior teeth was more than 2 mm, accounting for 58.25%, and 117 anterior teeth with dehiscence were found, accounting for 29.25%. Multilevel and multivariate Logistic regression showed age, jaw, tooth and site were the relevant factors to the position of alveolar crest. CONCLUSION: The position of alveolar crest of skeletal Angle class III patients who received periodontal bone augmentation surgery was lower than that of the general population, causing periodontal risks during decompensation orthodontics therapy before orthognathic surgery. The position of alveolar crest was lower in older patients than in younger patients, in mandibular teeth than in maxillary teeth, in canines than in central incisors or lateral incisors, and in central sites than in mesial sites or distal sites of labial side, which showed much higher risk.

Factors associated with long-term pessary use in women with symptomatic pelvic organ prolapse.

Objectives: This study aimed to evaluate the continuation rate and identify the factors associated with long-term pessary use, which are essential for counseling women with symptomatic pelvic organ prolapse (POP) seeking long-term pessary treatment. Methods: This prospective observational study included 277 patients who had successful pessary fittings between April 2015 and November 2016. All patients were followed until April 2018. Data analysis was performed with independent-samples t-tests, non-parametric tests, chi-square tests, and logistic regression. Results: The median (range) follow-up time was 26 (17-36) months; 76.5% of patients continued to use pessaries at the study endpoint. Sixty-one patients discontinued pessary use, and almost all of them (55/61, 90.2%) discontinued pessary use within the first 12 months after successful pessary fitting. A total vaginal length (TVL) < 7.5 cm (odds ratio [OR], 0.181; 95% confidence interval [CI], 0.062-0.524; p = 0.002) and a lower baseline Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6) score (OR, 0.974; 95% CI, 0.954-0.994; p = 0.013) were independent factors associated with pessary discontinuation. Conclusion: TVL ≥ 7.5 cm and a higher baseline POPDI-6 score were independent factors associated with long-term pessary use after successful fitting in women with symptomatic POP.

[Clinicopathological characteristics of HPV(+) oropharyngeal squamous cell carcinoma].

Objective: To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis. Methods: Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18). Results: The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA. Conclusions: OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.

Predictors for unsuccessful pessary fitting in women with symptomatic pelvic organ prolapse: a prospective study.

OBJECTIVE: To evaluate the success rate of vaginal pessary fitting and identify the risk factors associated with unsuccessful pessary fitting in a large cohort of patients with symptomatic pelvic organ prolapse (POP). DESIGN: Prospective observational study. SETTING: The Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Beijing, China. POPULATION: Women with symptomatic POP between May 2015 and December 2016 (n = 343). METHODS: A successful pessary fitting was defined as a patient fitted with a pessary at the initial fitting and continued use 2 weeks later. The independent samples t-test, non-parametric test, Chi-square test, Fisher's exact test, logistic regression and receiver operating characteristic curves were used for the data analysis. MAIN OUTCOME MEASURES: The success rate of vaginal pessary fitting and the risk factors associated with unsuccessful pessary fitting. RESULTS: 302 patients had successful pessary fitting (88.0% success rate). A higher body mass index [BMI; 24.7 ± 3.1 kg/m2 in the successful group versus 25.7 ± 3.8 kg/m2 in the unsuccessful group, odds ratio (OR) 1.174, 95% CI 1.055-1.307, P = 0.003] and a shorter TVL [8.0 (8-9) cm in the successful group versus 7.0 (6.8-8) cm in the unsuccessful group, OR 0.338, 95% CI 0.223-0.513, P < 0.001) were independent predictors of an unsuccessful pessary fitting. The receiver operating characteristic curve showed that patients with a total vaginal length (TVL) less than 7.3 cm had a higher unsuccessful pessary fitting rate (sensitivity = 0.82, specificity = 0.64). CONCLUSIONS: A higher BMI and shorter TVL were independent predictors of an unsuccessful pessary fitting. Patients with a TVL <7.3 cm are not appropriate candidates for a vaginal pessary. TWEETABLE ABSTRACT: A higher BMI and shorter TVL (<7.3 cm) were independent predictors of an unsuccessful pessary fitting.

Screening for general anxiety disorders in postmenopausal women with symptomatic pelvic organ prolapse.

OBJECTIVE: This study aimed to investigate the prevalence of general anxiety disorder (GAD) among postmenopausal women with symptomatic pelvic organ prolapse (POP) and to identify its associated factors. METHODS: A cross-sectional study was conducted among postmenopausal women with symptomatic POP. Sociodemographic data and medical histories were obtained. Participants completed the POP Quantification (POP-Q), the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and the Pelvic Floor Distress Inventory (PFDI-20) measures. Measures of GAD were obtained using the Generalized Anxiety Disorder-7 (GAD-7). The data were analyzed using independent sample t-tests, the Mann-Whitney U-test, χ2 tests, Fisher's exact tests and logistic regression. RESULTS: Of the 177 participants interviewed, 19.2% had symptoms of GAD. There were no statistically significant differences in the sociodemographic characteristics or the POP-Q stage between women with and without GAD (p > 0.05). GAD was significantly associated with higher PFDI-20 and PFIQ-7 subscale scores (p < 0.05). After multiple logistic regression analyses, only the PFIQ-7 subscale UIQ-7 (odds ratio = 1.025, 95% confidence interval 1.007-1.043, p = 0.005) and the PFDI-20 subscale CRADI-8 (odds ratio = 1.025, 95% confidence interval 1.004-1.047, p = 0.021), which represented the impact on quality of life from lower urinary tract symptoms and the distress caused by bowel dysfunction, were risk factors that were independently associated with GAD. CONCLUSIONS: GAD is prevalent in almost one-fifth of postmenopausal women with symptomatic POP. GAD is not associated with the severity of the POP-Q stage but is associated with higher scores for lower urinary tract and bowel dysfunction caused by POP.

Depressive symptoms affect outcomes of pessary use in postmenopausal women with uterine prolapse.

OBJECTIVE: This study aimed to investigate the impact of depressive symptoms on successful pessary treatment for postmenopausal women with symptomatic pelvic organ prolapse (POP). METHODS: We performed a prospective study involving postmenopausal women with POP who visited our clinic seeking pessary treatment. Demographic information and medical histories were collected. The participants completed the following questionnaires at baseline and after 3 months of successful pessary use: (1) the Pelvic Floor Impact Questionnaire-7 (PFIQ-7); (2) the Pelvic Floor Distress Inventory (PFDI-20); and (3) the Patient Health Questionnaire-9 (PHQ-9). The data were analyzed with the independent samples t-test, Mann-Whitney U-test, χ2 test, Fisher's exact test, paired t-test or Wilcoxon signed-rank test as appropriate. RESULTS: In total, 102 (92.7%) participants who completed the entire study were included in the analysis. No significant differences were found in the sociodemographic or clinical characteristics between the 'positive' and 'negative' depressive symptom groups (p > 0.05). After 3 months of successful pessary treatment, the scores of the PFIQ-7 (including the Urinary Incontinence Questionnaire-7, the Colon Rectal Anal Impact Questionnaire-7 and the Pelvic Organ Prolapse Impact Questionnaire-7 subscales) and PFDI-20 (including the Pelvic Organ Prolapse Distress Inventory-6, the Colon Rectal Anal Distress Inventory-8 and the Urinary Distress Inventory-6 (UDI-6) subscales) were significantly decreased in all participants (p < 0.05). The PHQ-9 score was also significantly decreased (p < 0.001). However, the participants with depressive symptoms reported significantly less improvement post-treatment than those without depressive symptoms in the score of the PFDI-20 subscale UDI-6, which represented the degree of distress due to the lower urinary tract symptoms (p = 0.022). CONCLUSIONS: Both the quality of life and depressive symptom scores were significantly improved after 3 months of successful pessary use. We advocate making depressive symptom screening a regular indicator for assessing the effectiveness of conservative POP treatment.

Prognostic value of pathologic grade for patients with oral squamous cell carcinoma.

OBJECTIVE: The purposes of this study were to explore both the prognostic value of pathologic grade and the relationships between differentiation and clinicopathological characteristics in oral squamous cell carcinoma. METHODS: This retrospective cohort study included the records of 2036 patients with oral squamous cell carcinoma who were surgically treated from June 1999 to December 2011. Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards regression model were performed for statistical analysis. RESULTS: Many clinicopathological characteristics were associated with pathologic grade. Kaplan-Meier analysis showed that well-differentiated tumors had a better prognosis than the other two grades. Cox regression model showed that differentiation was an independent risk factor for prognosis in patients with early stage, but not with advanced stage. The predictive abilities of pathologic grade, T stage, N status, and lymph node ratio were similar, but the presence of extracapsular spread and perineural invasion were stronger prognostic factors than pathologic differentiation. CONCLUSIONS: Pathologic grade was found to be an independent risk factor for early-stage oral squamous cell carcinoma, but not for advanced stage. Many important clinicopathological characteristics were associated with histological classification; however, its prognostic value was limited.

[The expression and prognostic significance of microRNA-34a in Uygur and Han patients with chronic lymphocytic leukemia in Xinjiang Uygur Autonomous Region in China].

To investigate the expression of microRNA-34a (miR-34a) in patients with chronic lymphocytic leukemia (CLL) in Xinjiang Uygur and Han nationalities and its prognostic significance. Our data showed that miR-34a expression in Uygur and Han CLL patients was significantly higher than that in their respective healthy controls, while miR-34a levels were similar between Uygur and Han patients. By comparing with known prognostic factors, receiver operating characteristic (ROC) curves showed that miR-34a was a good predictive factor for the prognosis of CLL (demarcation value was 3.567 6). Survival analysis was further performed according to miR-34a expression level, that low expression of miR-34a translated into poor prognosis.

Towards a global cancer knowledge network: dissecting the current international cancer genomic sequencing landscape.

BACKGROUND: While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community. METHODS: A multi-item survey was conducted assessing demographics, clinical data collection, genomic platforms, privacy/ethics concerns, funding sources and data sharing barriers for sequencing initiatives globally. Additionally, respondents were asked as to provide the primary intent of their initiative (clinical diagnostic, research or combination). RESULTS: Of 107 initiatives invited to participate, 59 responded (response rate = 55%). Whole exome sequencing (P = 0.03) and whole genome sequencing (P = 0.01) were utilized less frequently in clinical diagnostic than in research initiatives. Procedures to identify cancer-specific variants were heterogeneous, with bioinformatics pipelines employing different mutation calling/variant annotation algorithms. Measurement of treatment efficacy varied amongst initiatives, with time on treatment (57%) and RECIST (53%) being the most common; however, other parameters were also employed. Whilst 72% of initiatives indicated data sharing, its scope varied, with a number of restrictions in place (e.g. transfer of raw data). The largest perceived barriers to data harmonization were the lack of financial support (P < 0.01) and bioinformatics concerns (e.g. lack of interoperability) (P = 0.02). Capturing clinical data was more likely to be perceived as a barrier to data sharing by larger initiatives than by smaller initiatives (P = 0.01). CONCLUSIONS: These results identify the main barriers, as perceived by the cancer sequencing community, to effective sharing of cancer genomic and clinical data. They highlight the need for greater harmonization of technical, ethical and data capture processes in cancer sample sequencing worldwide, in order to support effective and responsible data sharing for the benefit of patients.

DSP-enabled reconfigurable and transparent spectral converters for converging optical and mobile fronthaul/backhaul networks.

Dynamically reconfigurable and transparent signal spectral conversion is expected to play a vital role in seamlessly integrating traditional metropolitan optical networks and mobile fronthaul/backhaul networks. In this paper, a simple digital signal processing (DSP)-enabled spectral converter is proposed and extensively investigated, for the first time, which just utilizes a single standard dual-parallel Mach-Zehnder modulator (DP-MZM) driven by SDN-controllable RF signals and DC bias currents. As an important thrust of the paper, optimum operating conditions of the proposed converter are analytically identified, statistically examined and experimentally verified. Optimum operating condition-supported spectral converter performances in IMDD-based network nodes are explored both theoretically and experimentally in terms of frequency detuning range-dependent conversion efficiency, spectral conversion-induced OSNR/power penalty and transparency to input signal characteristics. The proposed spectral converter has unique advantages including low configuration complexity, strict transparency, SDN-controllable performance reconfigurability and flexibility, as well as negligible spectral conversion-induced latency.

[Fibroblast growth factor receptor 1 propagates estrogen and fluid shear stress driven proliferation and differentiation response in MC3T3-E1 cells].

Fluid shear stress (FSS) and estrogen exposure positively regulate bone metabolism. Fibroblast growth factor receptor 1 (FGFR1) plays a vital role in FSS-induced osteogenesis. An in vitro experiment with MC3T3-E1 cells combined with microarray analysis aided us in identification of the genes differentially expressed in response to FSS and highlighted the role of FGFR1 in this process. Both estrogen exposure and FSS increase methyl thiazol tetrazolium (MTT) values and alkaline phosphatase (ALP) activity, as well as the levels of Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). The effects of estrogen exposure and FSS were cumulative. Treatment with PD166866 inhibitor of the FGFR1 reduced the MTT values, increased ALP activity, and increased the levels of Runx2 and OCN. To investigate the regulation of FGFR1 signaling in stressed cells, a number of key components of the mitogen-activated protein kinase (MAPK) cascade were quantitatively examined. Neither estrogen nor FSS change the protein expression of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinases (JNK) or p38, but positively influence their phosphorylation levels. Treatment with the FGFR1 inhibitor induced an increase in ERK phosphorylation levels only. In summary, estrogen exposure and FSS have a synergistic effect in osteogenesis. FGFR1 promotes osteoblast proliferation and inhibits the differentiation of osteoblasts. In MC3T3-E1 cells, FGFR1 signaling responds to independent and combined effects of estrogen and FSS. MAPK cascades participate in osteogenesis, but only the ERK signaling pathway responds to FGFR1.

Quantification of sialic acids in red meat by UPLC-FLD using indoxylsialosides as internal standards.

Herein we describe a UPLC-FLD-based method for the quantification of the sialic acid content of red meat, using a synthetic neuraminic acid derivative as an internal standard. X-Gal-α-2,6-N-propionylneuraminic acid was synthesized via a chemoenzymatic pathway and its hydrolytic stability was characterized. Known quantities of this compound were incubated with samples of red meat under sialic acid-releasing conditions. The released sialic acids were derivatized, analyzed by UPLC-FLD, and the Neu5Ac/Neu5Gc content of the meat sample was determined by comparison with the internal standard. A number of red meats were analyzed by this method with the following results (Neu5Ac µg/g tissue, Neu5Gc µg/g tissue ± s.d.): pork (68 ± 3, 15.2 ± 0.7), beef (69 ± 8, 36 ± 5), lamb (46 ± 2, 33 ± 1), rabbit (59 ± 2, 0.4 ± 0.4), and hare (50 ± 4, 1 ± 1). We envisage that this methodology will find application in investigating the health effects of dietary Neu5Gc. Graphical abstract ᅟ.

Cloning, characterization, expression, and feeding response of thyrotropin receptor in largemouth bass (Micropterus salmoides).

Thyrotropin receptor (TSHR) is a G-protein-coupled receptor that regulates the synthesis, storage, and secretion of thyroid hormones in the thyroid tissue. The aims of the present study were to characterize the full-length TSHR cDNA in largemouth bass (Micropterus salmoides), and to determine the TSHR gene transcription levels in different tissues. In addition, the response of TSHR transcription levels to daily feeding in thyroid tissue was investigated. The results showed that the full-length cDNA sequence was 2743 bp with an open reading frame of 2340 bp encoding a 779-amino acid peptide. BLAST analysis indicated that the amino acid sequence displayed 58.4-90.2% identity and 5.6-125.8 divergence, compared with other known fish species. The most abundant TSHR transcription levels were found in the spleen, head kidney, and kidney. Feeding did not affect the transcription level of TSHR in thyroid tissue over the course of the day. Thus, the current study suggests that there was no relationship between daily nutritional status and TSHR transcription level in the thyroid tissue of largemouth bass. The spleen, head kidney, and kidney exhibited the most abundant TSHR transcription levels.