Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

BACKGROUND AND PURPOSE: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. METHODS: Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). RESULTS: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. CONCLUSION: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

Efficacy of Laser Acupuncture for Treatment of Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize and systematically analyze the efficacy of laser acupuncture (LA) interventions in reducing pain scores in patients suffering from chronic low back pain (LBP). METHODS: PubMed, EMBASE, and Scopus databases were searched for randomized controlled trials, published in peer-reviewed journals, and reporting LA interventions in patients with chronic LBP. All included studies had a comparison group of patients, receiving placebo treatment, sham intervention, conventional therapy, or no treatment. The outcome of interest was the pain intensity score. Pooled effect estimates were calculated using random-effects models and reported as weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: A total of 20 studies were included. Compared to the control group, patients who underwent LA experienced a significant reduction in reported pain scores immediately after completing the treatment (WMD -1.14, 95% CI: -1.68 to -0.61). High dose of LA was associated with a more significant decrease in the pain scores (WMD -1.40, 95% CI: -1.94 to -0.85; N = 15, I2 = 81.0%). However, reported pain scores of patients who received LA were statistically similar to those of the control group at short-term (4-8 weeks after the treatment) and long-term (12 months) follow-ups. CONCLUSIONS: In patients with chronic LBP, LA may help in alleviating pain immediately after the treatment. However, this effect does not appear to be sustained on later follow-up assessments. Consequently, patients should be informed about the potential limitations of the treatment in providing lasting pain relief.

A 4-gene-based hypoxia signature is associated with tumor immune microenvironment and predicts the prognosis of pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood. METHODS: The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score. RESULTS: We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor. CONCLUSIONS: In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.

Transcriptome analysis reveals the pigmentation related genes in four different shell color strains of the Manila clam Ruditapes philippinarum.

Ruditapes philippinarum is an important marine bivalve species. In this study, we conducted the RNA-seq of four different shell color strains of the R. philippinarum and investigated the analysis of the differential expression patterns of specific genes associated with pigmentation. The maximum different genes was 13 between WZ vs O, WZ vs W and WZ vs O have same numbers of different genes, was 5, Z vs W has 4 genes of 18 DEGs, W vs O just have two DEGs, while there is no DEGs between WZ vs Z. The synthesis of melanin plays important roles in the pigmentation of the shell and is closely related to the formation of the surface pattern. We speculate the possible involvement of porphyrin and chlorophyll metabolism combined with calcium signaling pathway in shell color determination. This study sheds light on the pigmentation and coloration mechanism of the Manila clam.

Intrinsic chirp analysis of a single dual-drive silicon PAM-4 optical modulator.

We propose an analytical model to investigate the intrinsic frequency chirp with the method of 4-level pulse-amplitude-modulation (PAM-4) optical modulation by driving a single dual-drive silicon optical modulator. With the analytical model, we calculate the chirp parameters of this PAM-4 generation numerically. The intensity and phase of output signal changes with the PAM levels' switching, which results in the frequency chirp. We find that the modulator operating at different quadrature points (Q- and Q+) will have different frequency chirp behavior. The Q- modulator has mainly negative chirp parameters while Q+ modulator has mainly positive chirp parameters. We characterize the eye diagrams and BER of the optical PAM-4 signals generated by the Q- and Q+ modulator at the modulation rates of 25 Gbaud and 32 Gbaud, respectively, for both back-to-back and 2 km transmission in single mode fiber. The BER results show the Q- modulator has a small power penalty attribute to the positive fiber dispersion, which is suited for the short-distance transmission in data center application.

On-chip broadband silicon thermo-optic 2☓2 four-mode optical switch for optical space and local mode switching.

We present a silicon thermo-optic 2☓2 four-mode optical switch optimized for optical space switching plus local optical mode switching. Four asymmetric directional couplers are utilized for mode multiplexing and de-multiplexing. Sixteen 2☓2 single-mode optical switches based on balanced thermally tunable Mach-Zehnder interferometers are exploited for switching function. The measured insertion losses are 8.0~12.2 dB and the optical signal-to-noise ratios are larger than 11.2 dB in the wavelength range of 1525~1565 nm. The optical links in "all-bar" and "all-cross" states exhibit less than 2.0 dB and 1.4 dB power penalties respectively below 10-9 bit error rates for 40 Gbps data transmission.

Four-port mode-selective silicon optical router for on-chip optical interconnect.

We propose and demonstrate a four-port mode-selective optical router on a silicon-on-insulator platform. The passive routing property ensures that the router consumes no power to establish the optical links. For each port, input signals with different modes are selectively routed to the target ports through the pre-designed architecture. In general, the device intrinsically supports broadcasting of multiplexed signals from one port to the other three ports through mode division multiplexing. In some applications, the input signal from one port would only be sent to another port as in reconfigurable optical routers. The prototype is constructed by mode multiplexers/de-multiplexers and single-mode interconnect waveguides between them. The insertion losses for all optical links are lower than 8.0 dB, and the largest optical crosstalk values are lower than -18.7 dB and -22.0 dB for the broadcasting and port-to-port routing modes, respectively, at the wavelength range of 1525-1565 nm. In order to verify the routing functionality, a 40-Gbps bidirectional data transmission experiment is performed. The device offers a promising building block for passive routing by utilizing the dimension of the modes.

Ultrafast physical random bit generation from a chaotic oscillator with a silicon modulator.

We demonstrate physical random bit (PRB) generation from two chaotic optoelectronic oscillators (OEOs) with silicon Mach-Zehnder and microring resonator modulators. The carrier-injection modulation and the beam interference provide the nonlinearity for the OEO. We digitalize the chaotic waveforms from the two OEOs at 40 GS/s with 8-bit resolution and use self-delay bitwise exclusive-or operation as a post-processing method. The randomness of the resulting 320 Gbps PRB sequences is verified by the National Institute of Standards and Technology Special Publication 800-22 statistical tests. With the progress of silicon photonic circuits, there is a potential to fabricate a monolithic chaotic OEO chip for compact PRB generation.

Understanding the influence of individual variables contributing to multivariate outliers in assessments of data quality.

Mahalanobis distance is often recommended to identify patients or clinical sites that are considered unusual in clinical trials. Patients extreme in one or more covariates may be considered outliers in that they reside some distance from the multivariate mean, which can be thought of as the center of the data cloud. Less often discussed, patients whose data are believed to be "too good to be true" are located near the centroid as inliers. In order to efficiently investigate these anomalies for potential lapses in data quality, it is important to understand how the individual variables contribute to each multivariate outlier. There is a lack of literature describing a reasonable workflow for identification of outliers and their subsequent investigation to understand how each variable contributes to an observation being considered extreme. We describe how to identify multivariate inliers and outliers, classify outliers according to varying levels of severity, and summarize the contributions of variables using principal components in a manner that is accessible to a wide audience with straightforward interpretation. We illustrate how numerous data visualizations, including Pareto plots, can facilitate further review even in studies containing numerous observations and variables. We illustrate these methodologies using data from a multicenter clinical trial.

Optical PAM-4 signal generation using a silicon Mach-Zehnder optical modulator.

An analytic model is proposed to study the linearity performance of the silicon Mach-Zehnder optical modulator. According to the simulation results, we optimize the width of the silicon rib waveguide and the location of the PN junction to improve the linearity performance. The fabricated silicon Mach-Zehnder optical modulator has a spurious free dynamic range of 113.3 dB.Hz2/3 and 88.9 dB.Hz1/2 for the third-order intermodulation distortion and the second-order harmonic distortion. We also demonstrate the optical four-level pulse-amplitude-modulation (PAM-4) signal generation through the device. The generated optical PAM-4 signal is characterized at the rates up to 35 Gbaud. The BERs of the optical PAM-4 signals can reach 5.2╳10-6 at 20 Gbaud and 6.6╳10-5 at 32 Gbaud, which are much lower than the threshold of hard decision forward error correction (3.8 ╳10-3).

Optical switch compatible with wavelength division multiplexing and mode division multiplexing for photonic networks-on-chip.

We propose a 2 × 2 multimode optical switch, which is composed of two mode de-multiplexers, n 2 × 2 single-mode optical switches where n is the number of the supported spatial modes, and two mode multiplexers. As a proof of concept, asymmetric directional couplers are employed to construct the mode multiplexers and de-multiplexers, balanced Mach-Zehnder interferometer is utilized to construct the 2 × 2 single-mode optical switches. The fabricated silicon 2 × 2 multimode optical switch has a broad optical bandwidth and can support four spatial modes. The link-crosstalk for all four modes is smaller than -18.8 dB. The inter-mode crosstalk for the same optical link is less than -22.1 dB. 40 Gbps data transmission is performed for all spatial modes and all optical links. The power penalties for the error-free switching (BER<10-9) at 25 Gbps are less than 1.8 dB for all channels at the wavelength of 1550 nm. The power consumption of the device is 117.9 mW in the "cross" state and 116.2 mW in the "bar" state. The switching time is about 21 µs. This work enables large-capacity multimode photonic networks-on-chip.

Microring modulator matrix integrated with mode multiplexer and de-multiplexer for on-chip optical interconnect.

We experimentally demonstrate a 4 × 4 microring modulator matrix integrated with the asymmetrical directional couplers based mode multiplexer and de-multiplexer photonic circuit for on-chip optical interconnect. The inter-mode optical crosstalk of the device is less than -20 dB in the wavelength range from 1525 nm to 1565 nm. Data transmission with a throughput capacity of 4 × 4 × 32 Gbps is achieved by utilizing four wavelengths and four spatial modes multiplexing. We envision this structure as a potential solution to increase the communication capacity for on-chip interconnect within limited chip area.

Silicon PAM-4 optical modulator driven by two binary electrical signals with different peak-to-peak voltages.

We demonstrate a silicon PAM-4 optical modulator, which is based on a symmetric Mach-Zehnder interferometer. Two uncorrelated binary electrical signals with different peak-to-peak voltages are applied to the phase shifters of the silicon optical modulator. Accordingly, two different phase shifts are generated in the two arms. After the permutation, there are totally four phase differences between the two arms and the output optical power has four levels. The device can work at 32 Gbaud in the wavelength range from 1525 to 1565 nm, which is promising for the next-generation high-speed silicon optical link.

Silicon 16-QAM optical modulator driven by four binary electrical signals.

We demonstrate a silicon 16-quadrature amplitude modulation (16-QAM) optical modulator. Unlike traditional 16-QAM optical modulator with two Mach-Zehnder modulators (MZMs) driven by two four-level electrical signals, the device is based on four MZMs driven by four binary electrical signals. With the simple electrical driving configuration, the device generates a 16-QAM optical signal at 20 Gbaud with an error vector magnitude of 13.7%.

Method to improve the linearity of the silicon Mach-Zehnder optical modulator by doping control.

We optimize the linearity performance of silicon carrier-depletion Mach-Zehnder optical modulator through controlling the doping concentration. The optical field distribution in the waveguide is a Gaussian-like distribution. As the doping concentration increases, the dynamic depletion width of the PN junction under the same modulation signal will decrease, and the integration width of the overlap between the Gaussian-like optical field distribution and the depletion region will become smaller. Therefore the modulated signal has less nonlinear components. Our simulation results proved this analysis. We also fabricated different devices with different doping concentrations. By adopting a ten times doping concentration, the spurious free dynamic range (SFDR) for third-order intermodulation distortion (TID) increases from 109.2 dB.Hz2/3 to 113.7 dB.Hz2/3 and the SFDR for second harmonic distortion (SHD) increases from 87.6 dB.Hz1/2 to 97.5 dB.Hz1/2 at a driving frequency of 2 GHz. When the driving frequency is 20 GHz, the SFDRs for TID and SHD distortions are 110.3 dB.Hz2/3 and 96 dB.Hz1/2, respectively.

Reconfigurable nonblocking 4-port silicon thermo-optic optical router based on Mach-Zehnder optical switches.

We demonstrate a reconfigurable nonblocking 4-port silicon thermo-optic optical router based on Mach-Zehnder optical switches. For all optical links in its 9 routing states, the optical signal-to-noise ratios are larger than 15 dB in the wavelength range from 1525 to 1565 nm. Each optical link of the optical router can manipulate 50 wavelength-division-multiplexing channels with the data rate of 32 Gbps for each channel in the same wavelength range. Its average energy efficiency is about 16.3 fJ/bit, and its response time is about 19 µs.

Structural characterization and expression analysis of a novel cysteine protease inhibitor from Haliotis discus hannai Ino.

The sequence of the cysteine protease inhibitor gene of Haliotis discus hannai (designated HdCpi) was determined using the RACE method. The full-length HdCpi cDNA is 1049 bp long, and contains an open reading frame of 813 bp, encoding a 271-amino-acid protein with a calculated molecular mass of 29.83 kDa and an isoelectric point of 8.57. The deduced amino acid sequence of HdCpi contains two cystatin-like domains, and each has the structural features of the cystatin family, including three evolutionarily conserved motifs known to interact with the active sites of cysteine peptidases: the Gly residue at the N-terminus (Gly(65) and Gly(160)), the Gln-X-Val-X-Gly motif (Q(106)IVSG(110) and Q(202)VVAG(206)), and the less conserved motif at the C-terminus (S(136)W(137) and A(254)W(255)). Many putative transcription-factor-binding sites involved in the immune system and cancer occur in the promoter region of HdCpi. Quantitative real-time RT-PCR detected HdCpi expression in all the tissues examined and in the gills of abalone challenged with the bacterium Vibrio anguillarum. HdCpi transcripts were expressed in the mantle, gill, digestive tract, hemocytes, and muscle, and increased HdCpi expression was observed after bacterial stimulation. These results suggest that HdCpi is a biologically active protease inhibitor that is likely to be involved in the antibacterial response of the abalone.

XOR and XNOR operations at 12.5 Gb/s using cascaded carrier-depletion microring resonators.

We report the implementation of the XOR and XNOR logical operations using an electro-optic circuit, which is fabricated by CMOS-compatible process in the silicon-on-insulator (SOI) platform. The circuit consists of two cascaded add-drop microring resonators (MRRs), which are modulated through electric-field-induced carrier depletion in reverse biased pn junctions embedded in the ring waveguides. The resonance wavelength mismatch between the two nominally identical MRRs caused by fabrication errors is compensated by thermal tuning. Simultaneous bitwise XOR and XNOR operations of the two electrical modulating signals at the speed of 12.5 Gb/s are demonstrated. And 20 Gb/s XOR operation at one output port of the circuit is achieved. We explain the phenomena that one half of the resonance regions of the device are much more sensitive to the round-trip phase shift in the ring waveguides than the other half resonance regions. Characteristic graphs with logarithmic phase coordinate are proposed to analyze the sensitivity of the demonstrated circuit, as well as several typical integrated optical structures. It is found that our circuit with arbitrary chosen parameters has similar sensitivity to MRRs under the critical coupling.

Demonstration of electro-optic half-adder using silicon photonic integrated circuits.

We report a silicon photonic integrated circuit which can perform the operation of half-adder based on two cascaded microring resonators (MRRs). PIN diodes embedded around MRRs are employed to achieve the carrier injection modulation. Two electrical pulse sequences representing the two operands of the half-add operation are applied to PIN diodes to modulate two MRRs through the plasma dispersion effect. The final operation results of bitwise Sum and Carry operation are output at two different output ports of the device. Microheaters fabricated on the top of MRRs are employed to compensate two MRRs resonance mismatch caused by the fabrication error through the thermo-optic effect. Addition operation of two bits with the operation speed of 100 Mbps is demonstrated.

Demonstration of a 3-bit optical digital-to-analog converter based on silicon microring resonators.

We propose an N-bit optical digital-to-analog converter based on silicon microring resonators (MRRs), which can transform an N-bit electrical digital signal to an optical analog signal. A 3-bit optical digital-to-analog convertor is fabricated as proof of concept through a CMOS-compatible process on a silicon-on-insulator platform. The silicon MRRs are modulated through the electric-field-induced carrier injection in forward biased PN junctions embedded in the ring waveguides. The electro-optical 3-dB bandwidths of the silicon MRRs are approximately 800 MHz. The device works well at a speed of 500 MSample/s under driving voltage swings of 0.75 V.