MSM Behavior Disclosure Networks and HIV Testing: An Egocentric Network Analysis Among MSM in China.

Men who have sex with men (MSM) disclose same-sex behaviors with others, creating disclosure networks. This study examined the characteristics of disclosure networks that are associated with HIV testing among MSM in China through an online nationwide survey. Name-generator questions were used to ask each participant ("ego") to nominate up to five social network members ("alters") with whom he had disclosed same-sex behaviors. Among the 806 men, the average disclosure network size was 4.05. MSM who reported larger disclosure networks were more likely to have been tested for HIV (aOR 1.21, 95% CI 1.08-1.34). The most common disclosure network alters were friends (45.1%), followed by sex partners (18.7%) and healthcare professionals (2.5%). Men who disclosed to healthcare professionals were more likely to test for HIV compared to men who disclosed to family members (aOR 5.43, 95% CI 2.11-14.04). Our findings can inform disclosure network-based interventions to promote MSM HIV testing

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

Association of gestational age at birth with subsequent suspected Developmental Coordination Disorder in early childhood

Importance. It remains unknown whether children born at different degrees of prematurity, early-term and post-term might have a higher risk of developing Developmental Coordination Disorder (DCD) compared to completely full-term children (39-40 gestational weeks). Objective. To differentiate between suspected DCD in children with different gestational ages based on a national representative sample in China. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study in China from 2018 to 2019. A total of 152,433 children from 2,403 public kindergartens in 551 cities of China aged 3-5 years old were included in the final analysis. The association between gestational age and motor performance was investigated. A multi-level regression model was developed to determine the strength of association for different gestational ages associated with suspected DCD when considering kindergartens as clusters. Main outcomes and measures. Children’s motor performance was assessed using the Little Developmental Coordination Disorder Questionnaire (LDCDQ), completed by parents. Gestational age was determined according to the mother’s medical records. Results. Of the 152,433 children aged 3-5 years old, 80,370 (52.7%) were male, and 72,063 (47.3%) were female. There were 45,052 children aged 3 years old (29.6%), 59,796 aged 4 years old(39.2%), and 47,585 children aged 5 years old (31.2%). The LDCDQ total scores for very-preterm (β=-1.74, 95%CI: -1.98, 1.50; p<0.001), moderately-preterm (β=-1.24, 95%CI: -1.60, -0.89; p<0.001), late-preterm (β=-0.92, 95%CI: -1.08, -0.76; p<0.001), early-term (β=-0.36, 95%CI: -0.46, -0.25; p<0.001) and post-term children (β=-0.47, 95%CI: -0.67, -0.26; p<0.001) were significantly lower than full-term children when adjusting for child, family and maternal health characteristics. The very-preterm (OR=1.35, 95%CI: 1.23,1.48; p<0.001), moderately-preterm (OR=1.18, 95%CI: 1.02, 1.36; p<0.001), late-preterm (OR =1.24, 95%CI: 1.16,1.32; p<0.001), early-term (OR =1.11, 95%CI: 1.06,1.16; p<0.001) and post-term children (OR =1.167, 95%CI: 1.07, 1.27; p<0.001) were more likely to fall in the suspected Developmental Coordination Disorder (DCD) category on the LDCDQ compared with completely full-term children after adjusting for the same characteristics. The associations between different gestational ages and suspected DCD were stronger in boys and older (5 year old) children (each p<0.05). Conclusions and relevance. We found significant associations between every degree of prematurity at birth, early-term and post-term birth with suspected DCD when compared with full-term birth. Our findings have important implications for understanding motor development in children born at different gestational ages. Long-term follow-up and rehabilitation interventions should be considered for early- and post-term born children

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma

Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment

VolcanoML: Speeding up End-to-End AutoML via Scalable Search Space Decomposition

End-to-end AutoML has attracted intensive interests from both academia and industry, which automatically searches for ML pipelines in a space induced by feature engineering, algorithm/model selection, and hyper-parameter tuning. Existing AutoML systems, however, suffer from scalability issues when applying to application domains with large, high-dimensional search spaces. We present VOLCANOML, a scalable and extensible framework that facilitates systematic exploration of large AutoML search spaces. VOLCANOML introduces and implements basic building blocks that decompose a large search space into smaller ones, and allows users to utilize these building blocks to compose an execution plan for the AutoML problem at hand. VOLCANOML further supports a Volcano-style execution model - akin to the one supported by modern database systems - to execute the plan constructed. Our evaluation demonstrates that, not only does VOLCANOML raise the level of expressiveness for search space decomposition in AutoML, it also leads to actual findings of decomposition strategies that are significantly more efficient than the ones employed by state-of-the-art AutoML systems such as auto-sklearn.ISSN:2150-809

A Csr-type regulatory system, including small non-coding RNAs, regulates the global virulence regulator RovA of Yersinia pseudotuberculosis through RovM.

The MarR-type regulator RovA controls expression of virulence genes of Yersinia pseudotuberculosis in response to environmental signals. Using a genetic strategy to discover components that influence rovA expression, we identified new regulatory factors with homology to components of the carbon storage regulator system (Csr). We showed that overexpression of a CsrB- or a CsrC-type RNA activates rovA, whereas a CsrA-like protein represses RovA synthesis. We further demonstrate that influence of the Csr system on rovA is indirect and occurs through control of the LysR regulator RovM, which inhibits rovA transcription. The CsrA protein had also a major influence on the motility of Yersinia, which was independent of RovM. The CsrB and CsrC RNAs are differentially expressed in Yersinia. CsrC is highly induced in complex but not in minimal media, indicating that medium-dependent rovM expression is mediated through CsrC. CsrB synthesis is generally very low. However, overexpression of the response regulator UvrY was found to activate CsrB production, which in turn represses CsrC synthesis independent of the growth medium. In summary, the post-transcriptional Csr-type components were shown to be key regulators in the co-ordinated environmental control of physiological processes and virulence factors, which are crucial for the initiation of Yersinia infections

Directing curli polymerization with DNA origami nucleators

The physiological or pathological formation of fibrils often relies on molecular-scale nucleators that finely control the kinetics and structural features. However, mechanistic understanding of how protein nucleators mediate fibril formation in cells remains elusive. Here, we develop a CsgB-decorated DNA origami (CB-origami) to mimic protein nucleators in Escherichia coli biofilm that direct curli polymerization. We show that CB-origami directs curli subunit CsgA monomers to form oligomers and then accelerates fibril formation by increasing the proliferation rate of primary pathways. Fibrils grow either out from (departure mode) or towards the nucleators (arrival mode), implying two distinct roles of CsgB: as nucleation sites and as trap sites to capture growing nanofibrils in vicinity. Curli polymerization follows typical stop-and-go dynamics but exhibits a higher instantaneous elongation rate compared with independent fibril growth. This origami nucleator thus provides an in vitro platform for mechanistically probing molecular nucleation and controlling directional fibril polymerization for bionanotechnology