Assessment of network module identification across complex diseases.

Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the 'Disease Module Identification DREAM Challenge', an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.

[Factors influencing recovery from childhood inguinal herniorrhaphy-induced vas deferens obstruction after microscopic vasovasostomy].

OBJECTIVE: To investigate the factors influencing the recovery from childhood inguinal herniorrhaphy (IH)-induced vas deferens obstruction following microscopic vasovasostomy. METHODS: We retrospectively analyzed the clinical data on 41 cases of microscopic vasovasostomy for obstructive azoospermia in our hospital from July 2015 to September 2018. All the patients had a history of inguinal hernia treated by IH in the childhood. We performed scrotal ultrasonography, semen analysis and seminal plasma biochemistry to confirm vas deferens obstruction preoperatively. If sperm was observed for ≥2 times in semen examination after vasovasostomy, we considered the vas deferens successfully unobstructed. RESULTS: Microscopic vasovasostomy was successfully completed in 39 of the cases, of which2 were lost to follow-up, with a follow-up rate of 94.8% (37/39). The patients, at the mean age of (25.54 ± 2.85) years and with body mass index (BMI) of (24.92 ± 2.79) kg/m2 and post-IH time of (18.97 ± 2.58) years, were followed up for (13.05 ± 3.74) months. Successful recovery from vas deferens obstruction was observed in 78.4% (29/37) of the patients after IH, 80.0% (16/20) in the < 26-year-olds, 76.5% (13/17) in the ≥26-year-olds (P = 0.795), 75.0% (12/16) in those with BMI < 24.92 kg/m2 , 81.0% (17/21) in those with BMI ≥24.92 kg/m2 (P = 0.807), 78.6% (11/14) in those with post-IH time of < 19 years, 18.3% (18/23) in those with post-IH time of ≥19 years (P = 0.982), 60.0% (12/20) in those with sperm and 82.4% (14/17) in those without sperm found intraoperatively (P = 0.428), 42.9% (3/7) in those treated by unilateral and 82.4% (26/30) in those by bilateral vasovasostomy (P = 0.027). Multivariate logistic regression analysis showed a close correlation between the operation side and postoperative recovery from vas deferens obstruction (P = 0.022). CONCLUSIONS: For male patients undergoing microscopic vasovasostomy for childhood IH-induced vas deferens obstruction, the operation side is an independent factor influencing postoperative recovery, while age, BMI, post-IH time, and intraoperative presence or absence of sperm are not significantly correlated with it.

Anti-myeloma activity and molecular logic operation by Natural Killer cells in microfluidic droplets.

Immune-targeted therapies that activate effector lymphocytes such as Natural Killer (NK) cells are currently being investigated for the treatment of Multiple myeloma (MM), the second most common form of hematological cancer. However, individual NK cells are highly heterogeneous in their cytolytic potential, making it difficult to detect, quantify and correlate the outcome of dynamic effector-target cell interactions at single cell resolution. Here, we present a microfluidic bioassay platform capable of activity-based screening of cellular and molecular immunotherapies. We identified distinct functional signatures associated with NK-MM cell interaction. The addition of immunomodulatory drug lenalidomide altered responses of NK-susceptible MM cells but not that of NK-tolerant MM cells. Antitumor cytotoxicity was significantly increased by the blockade of PD1/PDL1 axis as well as the clinically relevant cell line NK92, which were used to construct molecular logic functions (AND and NOT gates). A predictive agent-based mathematical model was developed to simulate progressive disease states and drug efficacy. The findings of the current study validate the applicability of this microfluidic cytotoxicity assay for immunotherapy screening, biocomputation and for future employment in detection of patient-specific cell response for precision medicine.

[Correlation of male libido with the levels of serum reproductive hormones].

OBJECTIVE: To investigate the correlation between male libido and the levels of serum reproductive hormones. METHODS: We collected the clinical data on 134 men complaining of low or decreased sexual desire at our clinic of andrology from January 2013 to July 2018. According to the scores on the 13-item Self-Rating Libido Scale for Males (SRLS-M), we divided the subjects into a low libido (n = 68) and a normal libido group (n = 66), none with thyroid and adrenal diseases, liver and kidney diseases, or administration of drugs affecting sexual function and reproductive hormones in the past two weeks. We compared the age, history and course of disease, SRLS-M scores, levels of serum T, E2, LH, FSH and PRL, and T/E2 ratio between the two groups, and analyzed the correlation of the parameters obtained with the SRLS-M scores of the patients by Pearson correlation analysis. RESULTS: Compared with the males of the normal libido group, the low-libido patients showed a significantly longer course of disease (ï¼»1.83 ± 0.44ï¼½ vs ï¼»2.91 ± 0.08ï¼½ yr, P < 0.05), but lower SRLS-M score (31.47 ± 1.28 vs 19.56 ± 0.89, P < 0.01), T level (ï¼»17.51 ± 3.68ï¼½ vs ï¼»11.46 ± 1.62ï¼½ nmol/L, P < 0.01) and T/E2 ratio (17.27 ± 3.94 vs 12.42 ± 1.38, P < 0.01). No statistically significant differences were found between the normal and low libido groups in age (ï¼»32.22 ± 2.29ï¼½ vs ï¼»31.98 ± 2.19ï¼½ yr) or the levels of E2 (ï¼»103.97 ± 15.70ï¼½ vs ï¼»94.45 ± 10.37ï¼½ pmol/L), FSH (ï¼»9.98 ± 5.26ï¼½ vs ï¼»7.43 ± 3.84ï¼½ IU/L), LH (ï¼»5.70 ± 3.17ï¼½ vs ï¼»5.20 ± 3.37ï¼½ IU/L), or PRL (ï¼»281.96 ± 82.68ï¼½ vs ï¼»371.85 ± 243.38ï¼½ mIU/L). Pearson correlation analysis showed that the SRLS-M scores of the patients in the normal and low libido groups were positively correlated with the T level (r = 0.329 and 0.535, P<0.01) and T/E2 ratio (r = 0.542 and 0.603, P<0.01), and so was the T level with E2 (r = 0.743 and 0.644, P<0.01) and T/E2 (r = 0.387 and 0.618, P<0.01). The areas under the ROC curves for T, E2 and T/E2 were 0.660, 0.527 and 0.669, respectively. A T/E2 ratio of 12.15－15.73 exhibited a relatively high sensitivity (>0.5) and specificity (>0.5) in the diagnosis of low libido. CONCLUSIONS: The T level and T/E2 ratio are important factors, and E2 may also be a factor, influencing male libido, which, however, is more correlated with T/E2. A T/E2 ratio of 12.15－15.73 may be an indicator of normal libido, while a lower or higher T/E2 ratio may suggests low libido.

High-efficient removal of methylene blue by zirconium-based organic frameworks modified with 1,3,5-benzenetricarboxylic acid: Characterization, performances, and mechanisms.

The vast discharge of methylene blue (MB) dye in industrial effluent, risks the ecological environment, thus making its removal unavoidable. Recently, metal organic frameworks (MOFs) due to their larger pore volume, surface area and easy synthesis have proved to be exceptionally promising materials for contaminant treatment. Based on 1,3,5-benzenetricarboxylic acid (BTC) as a modifier, a new composite material consisting of BTC and Zr-based MOF (UIO-66-BTC) was fabricated for the effective removal of MB from the effluent. Its synthesis and efficient application has been confirmed by characterization analysis. The influencing factors, adsorption isotherms, and adsorption kinetics of MB adsorption by adsorbent were studied. It was demonstrated that the removal rate of MB adsorption by UIO-66-BTC reached 98.45% and the adsorption amount reached 393.80 mg g-1 at temperature (298 K), pH 7, adsorbent dosage (0.5 g L-1), MB initial concentration (200 mg L-1), and contact time of 720 min, respectively. The maximum adsorption of MB by UIO-66-BTC was 20.827 times higher than that of UIO-66 (18.908 mg g-1). The experimental data fits with the pseudo-second-order kinetic model and Langmuir isotherm, implying that the adsorption process is a monolayer chemisorption process. The thermodynamic and regeneration experiments showed that the spontaneous process enhanced the adsorption of MB at lower temperatures and the adsorption efficiency of MB remained above 68% after five successive cycles. The mechanism of MB adsorption on adsorbents is mainly based on electrostatic interactions, pore filling, hydrogen bonding and π-π interactions. It is concluded that this new adsorbent can be effectively used to treat MB in effluents.