Future medical applications of single-cell sequencing in cancer

Advances in whole genome amplification and next-generation sequencing methods have enabled genomic analyses of single cells, and these techniques are now beginning to be used to detect genomic lesions in individual cancer cells. Previous approaches have been unable to resolve genomic differences in complex mixtures of cells, such as heterogeneous tumors, despite the importance of characterizing such tumors for cancer treatment. Sequencing of single cells is likely to improve several aspects of medicine, including the early detection of rare tumor cells, monitoring of circulating tumor cells (CTCs), measuring intratumor heterogeneity, and guiding chemotherapy. In this review we discuss the challenges and technical aspects of single-cell sequencing, with a strong focus on genomic copy number, and discuss how this information can be used to diagnose and treat cancer patients

AN ALTERNATIVE VIEW OF LOUDSPEAKER NONLINEARITIES USING THE HILBERT-HUANG TRANSFORM

ABSTRACT This paper presents a new approach to nonlinear loudspeaker characterization using the Hilbert-Huang transform (HHT). Based upon the empirical mode decomposition (EMD) and the Hilbert transform, the HHT decomposes nonlinear signals into adaptive bases which reveal nonlinear effects in greater and more reliable detail than current approaches. Conventional signal decomposition techniques such as Fourier and Wavelet techniques analyse nonlinear distortion using linear transform theory. This restricts the nonlinear distortion to harmonic distortion. This work shows that real nonlinear loudspeaker distortion is more complex. HHT offers an alternate view through the cumulative effects of harmonics and intra-wave amplitude-and-frequency modulation. The work calls into question the interpretation of nonlinear distortion through harmonics and points towards a link between physical sources of nonlinearity and amplitude-and-frequency modulation. The work furthermore questions the suitability of traditional signal analysis approaches while giving weight to the use HHT analysis in future work

Lack of sexual behavior disclosure may distort STI testing outcomes.

BACKGROUND: Men who have sex with men (MSM) globally have a high burden of curable sexually transmitted infections (STIs). MSM do not frequently receive rectal STI testing because of several barriers, such as not being out (disclosure of sexual behavior). We evaluate whether Chinese MSM select an STI test (rectal vs urethral) appropriate for their sexual behavior (insertive and/or receptive), and the interactions with being out. METHODS: This was a secondary analysis of data from a cross sectional MSM survey conducted at a multisite randomized controlled trial (RCT) (December 2018 to January 2019) around uptake of gonorrhea and chlamydia testing among Chinese MSM (N = 431). We collected socio demographics, relevant medical and sexual history, and disclosure of sexual behavior (outness). We estimated the decision to test and test choice, and the extent to which disclosure plays a role in decision making. RESULTS: Among 431 MSM, mean age was 28 years (SD = 7.10) and 65% were out to someone. MSM who indicated versatile sexual behavior and were out to someone had a 26.8% (95%CI = 6.1, 47.5) increased likelihood for selecting the rectal test vs the ure thral test, compared to those versatile and not out. Versatile MSM out to their health provider outside of the study context had a 29.4% (95%CI = 6.3, 52.6) greater likelihood for selecting the rectal STI test vs the urethral test, compared to versatile MSM not out to their health provider. CONCLUSIONS: Sexual behavior and outness may affect gonorrhea and chlamydia testing provision. Apart from clinicians, community based efforts may reduce stigma based barriers to testing

MEDALT: Single-cell copy number lineage tracing enabling gene discovery

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT

BreakTrans: Uncovering the genomic architecture of gene fusions

Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTran

Recent Developments in the UNO MK 3 Process–A Low Cost, Environmentally Benign Precipitating Process for CO2 Capture

AbstractSubstantial progress in the development of the UNO MK 3 process and it's cost reduction capabilities has been made since previously reported [1]. In particular, the recent results of two pilot plant trials of the process continue to demonstrate and confirm the major features of the UNO MK 3 process:Low overall cost (up to 50% less than the best amines)Multi-impurity capture and production of valuable by-products (no degradation products)Low energy of regeneration (less than 2.5 GJ/T CO2)Low volatility and environmental impact (SOx and NOx converted to fertilizer products)A good fit with existing global potassium markets (no additional potassium required)These new results are groundbreaking in terms of advancing the process; with no major barriers evident for scaling up the process from the current pilot scale (TRL 5) to larger scale demonstration (TRL 6/7) over the next few years

Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men in China:a study protocol for a three-arm cluster randomized controlled trial

BACKGROUND: Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men (MSM). A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM. Pay-it-forward offers an individual a gift (e.g., a free test) and then asks the same person if they would like to give a gift to another person. This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms - a pay-it-forward arm, a pay-what-you-want arm, and a standard of care arm. METHODS: Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing. Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization. Eligible participants will be born biologically male, aged 16 years or older, reporting previous anal sex with another man, having never participated in the pay-it-forward program, without previous gonorrhea and chlamydia testing in the past 12 months, and residing in China. Following a cluster randomized design, every cluster of ten participants will be randomly allocated into one of three arms: (1) a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate ("pay it forward") toward testing for future testers; (2) a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test; (3) a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing. The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records. Secondary outcomes include incremental cost per test, incremental cost per diagnosis, community connectedness, and social cohesion. Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95% confidence intervals with a margin of 20% increase defined as superiority. DISCUSSION: This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia. We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward. Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741725 . Registered on 12 November 2018

A Reconfigurable Quantum Local Area Network Over Deployed Fiber

Practical quantum networking architectures are crucial for scaling the connection of quantum resources. Yet quantum network testbeds have thus far underutilized the full capabilities of modern lightwave communications, such as flexible-grid bandwidth allocation. In this work, we implement flex-grid entanglement distribution in a deployed network for the first time, connecting nodes in three distinct campus buildings time-synchronized via the Global Positioning System (GPS). We quantify the quality of the distributed polarization entanglement via log-negativity, which offers a generic metric of link performance in entangled bits per second. After demonstrating successful entanglement distribution for two allocations of our eight dynamically reconfigurable channels, we demonstrate remote state preparation -- the first realization on deployed fiber -- showcasing one possible quantum protocol enabled by the distributed entanglement network. Our results realize an advanced paradigm for managing entanglement resources in quantum networks of ever-increasing complexity and service demands

Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China:a randomised controlled trial

BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health

Toward understanding and exploiting tumor heterogeneity

The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here