A muti-modal feature fusion method based on deep learning for predicting immunotherapy response.

Immune checkpoint therapy (ICT) has greatly improved the survival of cancer patients in the past few years, but only a small number of patients respond to ICT. To predict ICT response, we developed a multi-modal feature fusion model based on deep learning (MFMDL). This model utilizes graph neural networks to map gene-gene relationships in gene networks to low dimensional vector spaces, and then fuses biological pathway features and immune cell infiltration features to make robust predictions of ICT. We used five datasets to validate the predictive performance of the MFMDL. These five datasets span multiple types of cancer, including melanoma, lung cancer, and gastric cancer. We found that the prediction performance of multi-modal feature fusion model based on deep learning is superior to other traditional ICT biomarkers, such as ICT targets or tumor microenvironment-associated markers. In addition, we also conducted ablation experiments to demonstrate the necessity of fusing different modal features, which can improve the prediction accuracy of the model.

A unique circulating microRNA pairs signature serves as a superior tool for early diagnosis of pan-cancer.

Cancer remains a major burden globally and the critical role of early diagnosis is self-evident. Although various miRNA-based signatures have been developed in past decades, clinical utilization is limited due to a lack of precise cutoff value. Here, we innovatively developed a signature based on pairwise expression of miRNAs (miRPs) for pan-cancer diagnosis using machine learning approach. We analyzed miRNA spectrum of 15832 patients, who were divided into training, validation, test, and external test sets, with 13 different cancers from 10 cohorts. Five different machine-learning (ML) algorithms (XGBoost, SVM, RandomForest, LASSO, and Logistic) were adopted for signature construction. The best ML algorithm and the optimal number of miRPs included were identified using area under the curve (AUC) and youden index in validation set. The AUC of the best model was compared to previously published 25 signatures. Overall, Random Forest approach including 31 miRPs (31-miRP) was developed, proving highly efficient in cancer diagnosis across different datasets and cancer types (AUC range: 0.980-1.000). Regarding diagnosis of cancers at early stage, 31-miRP also exhibited high capacities, with AUC ranging from 0.961 to 0.998. Moreover, 31-miRP exhibited advantages in differentiating cancers from normal tissues (AUC range: 0.976-0.998) as well as differentiating cancers from corresponding benign lesions. Encouragingly, comparing to previously published 25 different signatures, 31-miRP also demonstrated clear advantages. In conclusion, 31-miRP acts as a powerful model for cancer diagnosis, characterized by high specificity and sensitivity as well as a clear cutoff value, thereby holding potential as a reliable tool for cancer diagnosis at early stage.

Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis.

Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980-0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.

BHF177 Suppresses Diabetic Neuropathic Pain by Blocking PKC/CaMKII/ERK1/2/CREB Signaling Pathway through Activating GABAB Receptor.

The gamma-aminobutyric acid type B (GABAB) receptor may participate in the development of diabetic neuropathic pain (DNP). BHF177 serves as a positive allosteric modulator of the GABAB receptor. In the current study, we sought to study the role of the BHF177-GABAB receptor in DNP and its underlying mechanism. Streptozotocin was adopted to induce a rat model of DNP, followed by determination of the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and glucose level. The effect of BHF177 on DNP by regulating the GABAB receptor in vivo was determined by the injection of BHF177 and/or CGP46381 (a GABAB receptor antagonist) into rat models of DNP. Hippocampal neuronal cells were isolated and cultured, and the neurons and DNP model rats were treated with activators of PKC (PMA), CaMKII (CaCl2), or ERK1/2 (EGF) to study the role of GABAB receptors in DNP via regulation of the NR2B-PKC-CaMKII-ERK-CREB pathway. BHF177 suppressed DNP symptoms by activating the GABAB receptors, as evidenced by increased PWT and PWL of DNP rats and the increased number of neurons expressing the GABAB receptor, but this effect was reversed by CGP46381 treatment. BHF177 treatment markedly repressed PKC, CaMKII, p-ERK1/2, and p-CREB expressions in the rat DNP model, but these suppressive effects were abrogated by treatments with PMA, CaCl2, or EGF treatment, respectively. To sum up, BHF177 suppresses DNP symptoms by blocking the PKC/CaMKII/ERK1/2/CREB signaling pathway to activate the GABAB receptors.

Direct Tomography of High-Dimensional Density Matrices for General Quantum States of Photons.

Quantum-state tomography is the conventional method used to characterize density matrices for general quantum states. However, the data acquisition time generally scales linearly with the dimension of the Hilbert space, hindering the possibility of dynamic monitoring of a high-dimensional quantum system. Here, we demonstrate a direct tomography protocol to measure density matrices of photons in the position basis through the use of a polarization-resolving camera, where the dimension of density matrices can be as large as 580×580 in our experiment. The use of the polarization-resolving camera enables parallel measurements in the position and polarization basis and as a result, the data acquisition time of our protocol does not increase with the dimension of the Hilbert space and is solely determined by the camera exposure time (on the order of 10 ms). Our method is potentially useful for the real-time monitoring of the dynamics of quantum states and paves the way for the development of high-dimensional, time-efficient quantum metrology techniques.

High-fidelity spatial mode transmission through a 1-km-long multimode fiber via vectorial time reversal.

The large number of spatial modes supported by standard multimode fibers is a promising platform for boosting the channel capacity of quantum and classical communications by orders of magnitude. However, the practical use of long multimode fibers is severely hampered by modal crosstalk and polarization mixing. To overcome these challenges, we develop and experimentally demonstrate a vectorial time reversal technique, which is accomplished by digitally pre-shaping the wavefront and polarization of the forward-propagating signal beam to be the phase conjugate of an auxiliary, backward-propagating probe beam. Here, we report an average modal fidelity above 80% for 210 Laguerre-Gauss and Hermite-Gauss modes by using vectorial time reversal over an unstabilized 1-km-long fiber. We also propose a practical and scalable spatial-mode-multiplexed quantum communication protocol over long multimode fibers to illustrate potential applications that can be enabled by our technique.

Performance of real-time adaptive optics compensation in a turbulent channel with high-dimensional spatial-mode encoding.

The orbital angular momentum (OAM) of photons is a promising degree of freedom for high-dimensional quantum key distribution (QKD). However, effectively mitigating the adverse effects of atmospheric turbulence is a persistent challenge in OAM QKD systems operating over free-space communication channels. In contrast to previous works focusing on correcting static simulated turbulence, we investigate the performance of OAM QKD in real atmospheric turbulence with real-time adaptive optics (AO) correction. We show that even though our AO system provides a limited correction, it is possible to mitigate the errors induced by weak turbulence and establish a secure channel. The crosstalk induced by turbulence and the performance of AO systems is investigated in two configurations: a lab-scale link with controllable turbulence, and a 340 m long cross-campus link with dynamic atmospheric turbulence. Our experimental results suggest that an advanced AO system with fine beam tracking, reliable beam stabilization, precise wavefront sensing, and accurate wavefront correction is necessary to adequately correct turbulence-induced error. We also propose and demonstrate different solutions to improve the performance of OAM QKD with turbulence, which could enable the possibility of OAM encoding in strong turbulence.

Switchable detector array scheme to reduce the effect of single-photon detector's deadtime in a multi-bit/photon quantum link.

We explore the use of a switchable single-photon detector (SPD) array scheme to reduce the effect of a detector's deadtime for a multi-bit/photon quantum link. The case of data encoding using M possible orbital-angular-momentum (OAM) states is specifically studied in this paper. Our method uses N SPDs with a controllable M × N optical switch and we use a Monte Carlo-based method to simulate the quantum detection process. The simulation results show that with the use of the switchable SPD array, the detection system can allow a higher incident photon rate than what might otherwise be limited by detectors' deadtime. For the case of M = 4, N = 20, a 50-ns deadtime for the individual SPDs, an average photon number per pulse of 0.1, and under the limit that at most 10 % of the photon-containing pulses are missed, the switchable SPD array will allow an incident photon rate of 2250 million counts/s (Mcts/s). This is 25 times the 90 Mcts/s incident photon rate that a non-switchable, 4-SPD array will allow. The increase in incident photon rate is more than the 5 times increase, which is the simple increase in the number of SPDs and the number of OAM encoding states (e.g., N/M = 20/4).

Single-End Adaptive Optics Compensation for Emulated Turbulence in a Bi-Directional 10-Mbit/s per Channel Free-Space Quantum Communication Link Using Orbital-Angular-Momentum Encoding.

A single-end adaptive-optics (AO) module is experimentally demonstrated to mitigate the emulated atmospheric turbulence effects in a bi-directional quantum communication link, which employs orbital angular momentum (OAM) for data encoding. A classical Gaussian beam is used as a probe to detect the turbulence-induced wavefront distortion in the forward direction of the link. Based on the detected wavefront distortion, an AO system located on one end of the link is used to simultaneously compensate for the forward and backward channels. Specifically, with emulated turbulence and when the probe is turned on, the mode purity of photons carrying OAM ℓ = 1 is improved by ~ 21 % with AO mitigation. We also measured the performance when encoding data using OAM {ℓ = -1, + 2} and {ℓ = -2, + 1} in the forward and backward channels, respectively, at 10 Mbit/s per channel with one photon per pulse on average. For this case, we found that the AO system could reduce the turbulence effects increased quantum-symbol-error-rate (QSER) by ~ 76 % and ~ 74 %, for both channels in the uni-directional and bi-directional cases, respectively. Similar QSER improvement is observed for the opposite direction channels in the bi-directional case.

Spatial sampling of terahertz fields with sub-wavelength accuracy via probe-beam encoding.

Recently, computational sampling methods have been implemented to spatially characterize terahertz (THz) fields. Previous methods usually rely on either specialized THz devices such as THz spatial light modulators or complicated systems requiring assistance from photon-excited free carriers with high-speed synchronization among multiple optical beams. Here, by spatially encoding an 800-nm near-infrared (NIR) probe beam through the use of an optical SLM, we demonstrate a simple sampling approach that can probe THz fields with a single-pixel camera. This design does not require any dedicated THz devices, semiconductors or nanofilms to modulate THz fields. Using computational algorithms, we successfully measure 128 × 128 field distributions with a 62-µm transverse spatial resolution, which is 15 times smaller than the central wavelength of the THz signal (940 µm). Benefitting from the non-invasive nature of THz radiation and sub-wavelength resolution of our system, this simple approach can be used in applications such as biomedical sensing, inspection of flaws in industrial products, and so on.

Using all transverse degrees of freedom in quantum communications based on a generic mode sorter.

The dimension of the state space for information encoding offered by the transverse structure of light is usually limited by the finite size of apertures. The widely used orbital angular momentum (OAM) number of Laguerre-Gaussian (LG) modes in free-space communications cannot achieve the theoretical maximum transmission capacity unless the radial degree of freedom is multiplexed into the protocol. While the methodology to sort the radial quantum number has been developed, the application of radial modes in quantum communications requires an additional ability to efficiently measure the superposition of LG modes in the mutually unbiased basis. Here we develop and implement a generic mode sorter that is capable of sorting the superposition of LG modes through the use of a mode converter. As a consequence, we demonstrate an 8-dimensional quantum key distribution experiment involving all three transverse degrees of freedom: spin, azimuthal, and radial quantum numbers of photons. Our protocol presents an important step towards the goal of reaching the capacity limit of a free-space link and can be useful to other applications that involve spatial modes of photons.

Hermite-Gaussian mode sorter.

The Hermite-Gaussian (HG) modes, sometimes referred to as transverse electromagnetic modes in free space, form a complete and orthonormal basis that have been extensively used to describe optical fields. In addition, these modes have been shown to be helpful in enhancing information capacity of optical communications as well as achieving super-resolution imaging in microscopy. Here we propose and present the realization of an efficient, robust mode sorter that can sort a large number of HG modes based on the relation between HG modes and Laguerre-Gaussian (LG) modes. We experimentally demonstrate the sorting of 16 HG modes, and our method can be readily extended to a higher-dimensional state space in a straightforward manner. We expect that our demonstration will have direct applications in a variety of fields including fiber optics, classical and quantum communications, as well as super-resolution imaging.

Demonstration of a 10 Mbit/s quantum communication link by encoding data on two Laguerre-Gaussian modes with different radial indices.

We experimentally demonstrate a 10 Mbit/s free-space quantum communication link using data encoding on orthogonal Laguerre-Gaussian (LG) modes with the same azimuthal index but different radial indices. Data encoding on two LGℓp modes (i.e., for ℓ=0, we encode ["0", "1"] as [p=0, p=1], and for ℓ=1, we encode ["0", "1"] as [p=0, p=1]) is demonstrated by employing directly modulated laser diodes and helical phase holograms. The quantum symbol error rate (QSER) of <5% is achieved at an encoding rate of 10 Mbit/s. Moreover, the influence of the circle radius (R) of the receiver phase pattern on registered photon rates and QSERs is investigated. Our results show that a receiver phase pattern whose R does not match the beam size of the LG modes would induce higher cross talk between the two encoded quantum branches.

Realization of a scalable Laguerre-Gaussian mode sorter based on a robust radial mode sorter.

The transverse structure of light is recognized as a resource that can be used to encode information onto photons and has been shown to be useful to enhance communication capacity as well as resolve point sources in superresolution imaging. The Laguerre-Gaussian (LG) modes form a complete and orthonormal basis set and are described by a radial index p and an orbital angular momentum (OAM) index ℓ. Earlier works have shown how to build a sorter for the radial index p or/and the OAM index ℓ of LG modes, but a scalable and dedicated LG mode sorter which simultaneous determinate p and ℓ is immature. Here we propose and experimentally demonstrate a scheme to accomplish complete LG mode sorting, which consists of a novel, robust radial mode sorter that can be used to couple radial modes to polarizations, an ℓ-dependent phase shifter and an OAM mode sorter. Our scheme is in principle efficient, scalable, and crosstalk-free, and therefore has potential for applications in optical communications, quantum information technology, superresolution imaging, and fiber optics.

Spatially multiplexed orbital-angular-momentum-encoded single photon and classical channels in a free-space optical communication link.

We experimentally demonstrate spatial multiplexing of an orbital angular momentum (OAM)-encoded quantum channel and a classical Gaussian beam with a different wavelength and orthogonal polarization. Data rates as large as 100 MHz are achieved by encoding on two different OAM states by employing a combination of independently modulated laser diodes and helical phase holograms. The influence of OAM mode spacing, encoding bandwidth, and interference from the co-propagating Gaussian beam on registered photon count rates and quantum bit error rates is investigated. Our results show that the deleterious effects of intermodal crosstalk effects on system performance become less important for OAM mode spacing Δ≥2 (corresponding to a crosstalk value of less than -18.5 dB). The use of OAM domain can additionally offer at least 10.4 dB isolation besides that provided by wavelength and polarization, leading to a further suppression of interference from the classical channel.

Sorting Photons by Radial Quantum Number.

The Laguerre-Gaussian (LG) modes constitute a complete basis set for representing the transverse structure of a paraxial photon field in free space. Earlier workers have shown how to construct a device for sorting a photon according to its azimuthal LG mode index, which describes the orbital angular momentum (OAM) carried by the field. In this paper we propose and demonstrate a mode sorter based on the fractional Fourier transform to efficiently decompose the optical field according to its radial profile. We experimentally characterize the performance of our implementation by separating individual radial modes as well as superposition states. The reported scheme can, in principle, achieve unit efficiency and thus can be suitable for applications that involve quantum states of light. This approach can be readily combined with existing OAM mode sorters to provide a complete characterization of the transverse profile of the optical field.

Recurrent facial palsy in Melkersson Rosenthal syndrome: total facial nerve decompression is effective to prevent further recurrence.

OBJECTIVE: To study the role of total facial nerve decompression in preventing further recurrence of facial palsy in Melkersson Rosenthal syndrome (MRS). METHODS: Total facial nerve decompression was performed on nine patients with recurrent facial palsy in MRS, and prednisolone treatment was given to 6 cases who declined surgery. They were incorporated into surgery group and control group, respectively. Patients in surgery group and control group were followed up for 5.4 ± 1.4 years (range, 4 to 8 years) and 6.0 ± 1.4 years (range, 4 to 8 years), respectively. RESULTS: Further episodes of facial palsy affected none of 9 cases (0.0%) in surgery group, while they affected 3 of 6 cases (50.0%) in control group, with significant difference (p<0.05). CONCLUSIONS: Total facial nerve decompression was effective to prevent further episodes of facial palsy in MRS.

Long-term outcomes of facial nerve schwannomas with favorable facial nerve function: tumor growth rate is correlated with initial tumor size.

OBJECTIVE: The study aimed to report long-term outcomes of facial nerve schwannomas (FNS) with favorable facial nerve function by observation, and to discuss about the relationship between initial tumor size and tumor growth. METHODS: 21 facial nerve schwannoma cases with favorable facial nerve function were managed by observation. They were divided into larger size group (size ≥10mm) and smaller size group (size <10mm) according to initial tumor size. RESULTS: They were followed up for 6.4±1.7years. 18 of 21 cases (85.7%) maintained House-Brackmann Grade III or better. Growth rate of the tumors in larger size group was 72.7%, much higher than 10% in smaller size group (p<0.05). CONCLUSIONS: Observation was feasible for most FNS with favorable facial nerve function, and growth rate of the tumors was associated with tumor size.