DANCE: a deep learning library and benchmark platform for single-cell analysis.

DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.

Joint representation of molecular networks from multiple species improves gene classification.

Network-based machine learning (ML) has the potential for predicting novel genes associated with nearly any health and disease context. However, this approach often uses network information from only the single species under consideration even though networks for most species are noisy and incomplete. While some recent methods have begun addressing this shortcoming by using networks from more than one species, they lack one or more key desirable properties: handling networks from more than two species simultaneously, incorporating many-to-many orthology information, or generating a network representation that is reusable across different types of and newly-defined prediction tasks. Here, we present GenePlexusZoo, a framework that casts molecular networks from multiple species into a single reusable feature space for network-based ML. We demonstrate that this multi-species network representation improves both gene classification within a single species and knowledge-transfer across species, even in cases where the inter-species correspondence is undetectable based on shared orthologous genes. Thus, GenePlexusZoo enables effectively leveraging the high evolutionary molecular, functional, and phenotypic conservation across species to discover novel genes associated with diverse biological contexts.

Room-Temperature Strong Coupling of Few-Exciton in a Monolayer WS2 with Plasmon and Dispersion Deviation.

Engineering room-temperature strong coupling of few-exciton in transition-metal dichalcogenides (TMDCs) with plasmons promises to construct compact and high-performance quantum optical devices. But it remains unimplemented due to their in-plane excitons. Here, we demonstrate the strong coupling of few-exciton within 10 in monolayer WS2 with the plasmonic mode with a large tangential component of the electric field tightly trapped around the sharp corners of an Au@Ag nanocuboid, the fewest number of excitons observed in the TMDC family so far. Furthermore, we for the first time report a significant deviation with a relative difference of up to 100.6% between the spectrum and eigenlevel splitting dispersions, which increases with decreasing coupling strength. It is also shown that the coupling strength obtained by the conventional concept of both being equal to the measured spectrum splitting is markedly overestimated. Our work enriches the understanding of strong light-matter interactions at room temperature.

Single-Cell Multimodal Prediction via Transformers.

The recent development of multimodal single-cell technology has made the possibility of acquiring multiple omics data from individual cells, thereby enabling a deeper understanding of cellular states and dynamics. Nevertheless, the proliferation of multimodal single-cell data also introduces tremendous challenges in modeling the complex interactions among different modalities. The recently advanced methods focus on constructing static interaction graphs and applying graph neural networks (GNNs) to learn from multimodal data. However, such static graphs can be suboptimal as they do not take advantage of the downstream task information; meanwhile GNNs also have some inherent limitations when deeply stacking GNN layers. To tackle these issues, in this work, we investigate how to leverage transformers for multimodal single-cell data in an end-to-end manner while exploiting downstream task information. In particular, we propose a scMoFormer framework which can readily incorporate external domain knowledge and model the interactions within each modality and cross modalities. Extensive experiments demonstrate that scMoFormer achieves superior performance on various benchmark datasets. Remarkably, scMoFormer won a Kaggle silver medal with the rank of 24/1221 (Top 2%) without ensemble in a NeurIPS 2022 competition. Our implementation is publicly available at Github.

Highly Efficient Single-Exciton Strong Coupling with Plasmons by Lowering Critical Interaction Strength at an Exceptional Point.

The single-exciton strong coupling with the localized plasmon mode (LPM) at room temperature is highly desirable for exploiting quantum technology. However, its realization has been a very low probability event due to the harsh critical conditions, severely compromising its application. Here, we present a highly efficient approach for achieving such a strong coupling by reducing the critical interaction strength at the exceptional point based upon the damping inhibition and matching of the coupled system, instead of enhancing the coupling strength to overcome the system's large damping. Experimentally, we compress the LPM's damping linewidth from about 45 nm to about 14 nm using a leaky Fabry-Perot cavity, a good match to the excitonic linewidth of about 10 nm. This method dramatically relaxes the harsh requirement in mode volume by more than an order of magnitude and allows a maximum direction angle of the exciton dipole relative to the mode field of up to around 71.9°, significantly improving the success rate of achieving the single-exciton strong coupling with LPMs from about 1% to about 80%.

Fischer's base-triggered formal (3+2) cycloadditions with 3-isothiocyanato oxindoles as acceptor-donor synthons.

Herein, previously unreported Fischer's base reactants serving as useful 2C building blocks in (3+2) cycloaddition reactions to build a library of bispiro[Fischer's base-oxindole] hybrids are described. These structurally intriguing products containing three adjacent quaternary stereocentres were smoothly afforded in up to 82% yield and >20 : 1 dr under catalyst-free conditions. Notably, the present protocol firstly employs 3-isothiocyanato oxindole serving as an acceptor and then as a donor in the formal (3+2) cycloadditions, allowing practical, straightforward access to structurally diverse cycloadducts. This work expands the applicability scope of 3-isothiocyanato oxindoles, which have been limited to behaving as donor/acceptor-based synthons in cycloadditions in previous work.

Auricular therapy for primary dysmenorrhea: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea (PD) is a common problem among women. It is defined as any degree of perceived cramping pain during menstruation without any evident pathology. Auricular therapy (AT), a widely used alternative medical treatment method as part of traditional Chinese acupuncture, lacks reliable evidence to support its safety and effectiveness for PD. We aimed to conduct a meta-analysis to investigate the efficacy and safety of AT in PD and to investigate possible factors impacting the particular efficacy of AT in PD by meta-regression. METHODS: This protocol followed the PRISMA guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The following 9 sources will be searched for randomized control trials of AT for PD: the Cochrane Central Register of Controlled Trials, PubMed, Medline, Embase, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure, Chinese Science and Technology Periodicals (VIP) database and WanFang Database from inception to January 1, 2023. Primary outcomes include visual rating scales and clinical efficacy rates, while secondary outcomes include endocrine hormone indicators related to PD and adverse events. Two reviewers will work independently on study selection, data extraction, and coding, including the risk of bias assessment in the included studies. While conducting a meta-analysis, Review Manager version 5.3 will be employed. Otherwise, a descriptive analysis will be performed. The results will be displayed as a risk ratio with 95% confidence intervals for dichotomous data as well as weight mean difference or standardized mean difference with 95% confidence intervals for continuous data. RESULTS: This study's protocol will investigate the efficacy and safety of AT in the treatment of PD in a systematic way. CONCLUSION: This systematic evaluation will objectively and systematically assess the efficacy and safety of AT in PD based on the available evidence, as well as provides clinicians with evidence to support the treatment of the disease.

Application of fMRI techniques in the study of acupuncture for gynecological diseases: A review.

Acupuncture therapy, as a characteristic of Chinese medical therapy, has a long history and remarkable effect in the treatment of gynecological diseases, and so far, it has formed a complete treatment system, but its efficacy and mechanism of action remain unclear. Functional magnetic resonance imaging, a visual technique, provides an objective basis for the study of acupuncture in the treatment of gynecological diseases. This paper summarizes the current status of acupuncture in the treatment of gynecological diseases and summarizes the progress of functional magnetic resonance imaging research related to acupuncture in the treatment of gynecological diseases in the past 10 years, mainly including the common types of gynecological diseases in acupuncture clinics, and the commonly used acupuncture points. This study is expected to provide literature support for subsequent research on the central mechanisms of acupuncture in the treatment of gynecological diseases.

PyGenePlexus: a Python package for gene discovery using network-based machine learning.

SUMMARY: PyGenePlexus is a Python package that enables a user to gain insight into any gene set of interest through a molecular interaction network informed supervised machine learning model. PyGenePlexus provides predictions of how associated every gene in the network is to the input gene set, offers interpretability by comparing the model trained on the input gene set to models trained on thousands of known gene sets, and returns the network connectivity of the top predicted genes. AVAILABILITY AND IMPLEMENTATION: https://pypi.org/project/geneplexus/ and https://github.com/krishnanlab/PyGenePlexus. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Accurately modeling biased random walks on weighted networks using node2vec.

MOTIVATION: Accurately representing biological networks in a low-dimensional space, also known as network embedding, is a critical step in network-based machine learning and is carried out widely using node2vec, an unsupervised method based on biased random walks. However, while many networks, including functional gene interaction networks, are dense, weighted graphs, node2vec is fundamentally limited in its ability to use edge weights during the biased random walk generation process, thus under-using all the information in the network. RESULTS: Here, we present node2vec+, a natural extension of node2vec that accounts for edge weights when calculating walk biases and reduces to node2vec in the cases of unweighted graphs or unbiased walks. Using two synthetic datasets, we empirically show that node2vec+ is more robust to additive noise than node2vec in weighted graphs. Then, using genome-scale functional gene networks to solve a wide range of gene function and disease prediction tasks, we demonstrate the superior performance of node2vec+ over node2vec in the case of weighted graphs. Notably, due to the limited amount of training data in the gene classification tasks, graph neural networks such as GCN and GraphSAGE are outperformed by both node2vec and node2vec+. AVAILABILITY AND IMPLEMENTATION: The data and code are available on GitHub at https://github.com/krishnanlab/node2vecplus_benchmarks. All additional data underlying this article are available on Zenodo at https://doi.org/10.5281/zenodo.7007164. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Up-regulated small-conductance calcium-activated potassium currents contribute to atrial arrhythmogenesis in high-fat feeding mice.

AIMS: Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS. METHODS AND RESULTS: Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023). CONCLUSION: Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.

Acupuncture for Crohn's disease: protocol for a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Crohn's disease (CD) is a chronic recurrent gastrointestinal disorder with a high incidence of inflammation due to intestinal inflammation. Acupuncture is commonly used as an alternative therapy for patients with CD. The aim of this study was to design a systematic review and meta-analysis protocol, to provide guidance for the establishment of systematic evaluation and meta-analysis on the efficacy and safety of acupuncture on CD. METHODS: We will search PubMed, the Cochrane Library, Embase, Web of Science, and 4 Chinese databases: China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, and Chinese Biomedical Database to obtain randomized controlled trials of CD treated with acupuncture from inception to November 5, 2022. Primary outcome include CD symptoms severity and clinical efficacy, secondary outcome indicators include laboratory indicators or inflammatory markers, severity of endoscopic lesions, quality of life, and safety outcomes. We will analyze the data using RevMan V.5.4 software. Two reviewers will assess the risk of bias and study quality by the Cochrane Collaboration Risk of Bias Tool and GRADE methods, respectively. RESULTS: This systematic review and meta-analysis protocol will analyze the efficacy, symptom improvement, quality of life, and safety of acupuncture therapy for CD. CONCLUSION: This protocol outlines the planned scope and methodology of a forthcoming systematic review and meta-analysis to provide guidelines for a rigorous assessment of the efficacy and safety of acupuncture for the treatment of CD.

Primary immature teratoma in the liver with growing teratoma syndrome and gliomatosis peritonei: a rare case report.

BACKGROUND: Primary liver immature teratoma is extremely rare and only 4 cases have been reported, let alone with growing teratoma syndrome (GTS) and/or gliomatosis peritonei (GP). CASE PRESENTATION: Here, we report a case of a 44-year-old female presenting with progressive abdominal distension and elevated serum alpha fetal protein (AFP) level. CT/MRI scans revealed a large cystic-solid mass in the right lobe of the liver, accompanied with implant or metastasis in the abdominal cavity. Pathologic examination at biopsy suggested immature teratoma. After 4 cycles of chemotherapy, an MRI showed a slight increase in tumor size. Therefore, surgical resection of the right lobe of the liver was performed. The final histological diagnosis was a mature teratoma (tumor size 28 cm × 14 cm × 13 cm), with no residual immature component, and the diagnosis of GTS was considered. The patient continued to receive 2 courses of postoperative chemotherapy. An abdominal CT scan revealed innumerable miliary nodules in bilateral adnexal areas 2 months after surgery. Histologically, large numbers of mature glia were observed, supporting the diagnosis of GP. CONCLUSIONS: We report for the first time a case of primary liver immature teratoma with GTS and GP in an adult. Longer follow-up is needed to assess definitive efficacy.

Acupuncture Analgesia in Patients with Postoperative Neck Pain: A Protocol for Systematic Review and Meta-Analysis.

Background. There is a yearly increase in pain after neck surgery, which is accompanied by high consumption of opioids. However, the opioid addiction epidemic is one of the most serious public health problems worldwide. Therefore, it is important to find suitable alternatives for opioids. Acupuncture therapy has been found effective for some types of pain control. This protocol aims to evaluate the efficacy and safety of acupuncture therapy in the treatment of pain after neck surgery. Methods and Analysis. We will search eight electronic databases from their inception to April 2022. Only randomized controlled trials (RCTs) using manual acupuncture, auricular acupuncture, or electroacupuncture as major therapy will be included, regardless of whether the study was published in Chinese or English. The selection of studies and data extraction will be independently completed by at least two experienced reviewers with a master's degree. The methodological quality of the included studies will be assessed by the Cochrane risk-of-bias tool. For the meta-analysis, Review Manager Statistical (RevMan V.5.3) software will be used. The results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethics and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and presented at a relevant conference, and there is no need to obtain formal ethical approval. Trial Registration Number. PROSPERO registration number CRD42021281722.

Catalytic asymmetric Michael/cyclization reaction of 3-isothiocyanato thiobutyrolactone: an approach to the construction of a library of bispiro[pyrazolone-thiobutyrolactone] skeletons.

Here, we demonstrate the first example of 3-isothiocyanato thiobutyrolactone serving as a useful building block in the Michael/cyclization reaction with alkylidene pyrazolones for the enantioselective construction of optically active structural bispiro[pyrazolone-thiobutyrolactone] skeletons containing three contiguous stereocenters with two spiroquaternary stereocenters. These products were smoothly afforded in up to 90% yield, >20 : 1 dr and >99% ee with chiral squaramide as the catalyst under mild conditions. Notably, this is also the first example of the merger of a spirocyclic pyrazolone scaffold with a spirocyclic thiobutyrolactone scaffold, potentially useful in medicinal chemistry.

Room-Temperature Strong Coupling Between a Single Quantum Dot and a Single Plasmonic Nanoparticle.

A single quantum dot (QD) strongly coupled with a plasmonic nanoparticle yields a promising qubit for scalable solid-state quantum information processing at room temperature. However, realizing such a strong coupling remains challenging due to the difficulty of spatial overlap of the QD excitons with the plasmonic electric fields (EFs). Here, by using a transmission electron microscope we demonstrate for the first time that this overlap can be realized by integrating a deterministic single QD with a single Au nanorod. When a wedge nanogap cavity consisting of them and the substrate is constructed, the plasmonic EFs can be more effectively "dragged" and highly confined in the QD's nanoshell where the excitons mainly reside. With these advantages, we observed the largest spectral Rabi splitting (reported so far) of ∼234 meV for a single QD strong coupling with plasmons. Our work opens a pathway to the massive construction of room-temperature strong coupling solid qubits.

GenePlexus: a web-server for gene discovery using network-based machine learning.

Biomedical researchers take advantage of high-throughput, high-coverage technologies to routinely generate sets of genes of interest across a wide range of biological conditions. Although these technologies have directly shed light on the molecular underpinnings of various biological processes and diseases, the list of genes from any individual experiment is often noisy and incomplete. Additionally, interpreting these lists of genes can be challenging in terms of how they are related to each other and to other genes in the genome. In this work, we present GenePlexus (https://www.geneplexus.net/), a web-server that allows a researcher to utilize a powerful, network-based machine learning method to gain insights into their gene set of interest and additional functionally similar genes. Once a user uploads their own set of human genes and chooses between a number of different human network representations, GenePlexus provides predictions of how associated every gene in the network is to the input set. The web-server also provides interpretability through network visualization and comparison to other machine learning models trained on thousands of known process/pathway and disease gene sets. GenePlexus is free and open to all users without the need for registration.

Radiative coupling of two quantum emitters in arbitrary metallic nanostructures.

We propose a general formalism beyond Weisskopf-Wigner approximation to efficiently calculate the coupling matrix element, evolution spectrum and population evolution of two quantum emitters in arbitrary metallic nanostructures. We demonstrate this formalism to investigate the radiative coupling and decay dynamics of two quantum emitters embedded in the two hot spots of three silver nano-spheroids. The vacuum Rabi oscillation in population evolution and the anti-crossing behavior in evolution spectrum show strong radiative coupling is realized in this metallic nanostructure despite its strong plasmon damping. Our formalism can serve as a flexible and efficient calculation tool to investigate the distant coherent interaction in a large variety of metallic nanostructures, and may be further developed to handle the cases for multiple quantum emitters and arbitrary dielectric-metallic hybrid nanostructures.

Ring opening and skeletal reconstruction of 3-vinyl benzofuranone-chromone synthons: catalyst-free access to skeletally-diverse 2-pyridone and optically active imidazoline derivatives.

Herein is reported the first example of ring opening and skeletal reconstruction of 3-vinyl benzofuranone-chromones 1 as versatile synthons, which can react with ammonia or primary aliphatic amines as binucleophiles, for the eco-friendly and atom-economical synthesis of diverse and functionalized 2-pyridones 3 with potential biological activity in good to excellent yields (77-93%). When using optically active 1,2-diphenylethylenediamine 2 as the binucleophile, the in situ generated 2-pyridone intermediates are successfully transformed to novel optically active functionalized imidazoline derivatives 4 with high efficiency (up to 87% yield). In particular, this is the first report on the catalyst-free intramolecular cyclization occurring between an amide and a primary aliphatic amine for the construction of imidazoline molecules.

Suppressed Blinking and Polarization-Dependent Emission Enhancement of Single ZnCdSe/ZnS Dot Coupled with Au Nanorods.

Fluorescent quantum dots (QDs) have attracted extensive attention because of their promising applications in many fields such as quantum optics, optoelectronics, solid-state lighting, and bioimaging. However, photo-blinking, low emission efficiency, and instability are the drawbacks of fluorescent QD-based devices, affecting their optical properties and practical applications. Here, we report suppressed blinking, enhanced radiative rate, and polarization-dependent emission properties of single ZnCdSe/ZnS QDs assembled on the surface of Au nanorods (NRs). We found that the local surface plasmon (LSP) of Au NRs significantly regulates the excitation and emission properties of the composite ZnCdSe/ZnS QD-Au NRs (QD-Au NRs). The average number of photons emitted per unit time from single QD-Au NRs has been significantly enhanced compared with that of single ZnCdSe/ZnS QDs on the coverslip, accompanied by a drastically shortened lifetime and suppressed blinking. According to the experimental and simulation analysis, the photogenerated LSP field of Au NRs remarkably increases the excitation transition and the radiative rates of QD-Au NRs. Although the emission efficiency is slightly increased, the synergetic enhancement of excitation and radiative rates sufficiently competes with the nonradiative process to compensate for the low emission efficiency of QDs and ultimately suppress the photo-blinking of QD-Au NRs. Moreover, the polarization-dependent emission enhancement has also been observed and theoretically analyzed, demonstrating good consistency and confirming the contribution of excitation enhancement. Our findings present a practical strategy to improve the optical properties and stability of single QD-Au NR composite and provide essential information for a deep understanding of the interaction between emitters and the LSP field of metal nanoparticles.