Correction: Integrated silicon photonic MEMS.

[This corrects the article DOI: 10.1038/s41378-023-00498-z.].

Integrated silicon photonic MEMS.

Silicon photonics has emerged as a mature technology that is expected to play a key role in critical emerging applications, including very high data rate optical communications, distance sensing for autonomous vehicles, photonic-accelerated computing, and quantum information processing. The success of silicon photonics has been enabled by the unique combination of performance, high yield, and high-volume capacity that can only be achieved by standardizing manufacturing technology. Today, standardized silicon photonics technology platforms implemented by foundries provide access to optimized library components, including low-loss optical routing, fast modulation, continuous tuning, high-speed germanium photodiodes, and high-efficiency optical and electrical interfaces. However, silicon's relatively weak electro-optic effects result in modulators with a significant footprint and thermo-optic tuning devices that require high power consumption, which are substantial impediments for very large-scale integration in silicon photonics. Microelectromechanical systems (MEMS) technology can enhance silicon photonics with building blocks that are compact, low-loss, broadband, fast and require very low power consumption. Here, we introduce a silicon photonic MEMS platform consisting of high-performance nano-opto-electromechanical devices fully integrated alongside standard silicon photonics foundry components, with wafer-level sealing for long-term reliability, flip-chip bonding to redistribution interposers, and fibre-array attachment for high port count optical and electrical interfacing. Our experimental demonstration of fundamental silicon photonic MEMS circuit elements, including power couplers, phase shifters and wavelength-division multiplexing devices using standardized technology lifts previous impediments to enable scaling to very large photonic integrated circuits for applications in telecommunications, neuromorphic computing, sensing, programmable photonics, and quantum computing.

Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer: A case report.

BACKGROUND: Immune checkpoint inhibitor (ICI)-induced rheumatic immune-related adverse events (irAEs) have been infrequently reported, and the treatment of severe or refractory arthritis as irAEs has not been established yet. CASE SUMMARY: The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia. He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously. Physical examination revealed erythematous swelling in the distal interphalangeal joints, left shoulder, and both knees. He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes. Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative. The patient was diagnosed with psoriatic arthritis (PsA) and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation. However, despite 1 wk of methylprednisolone treatment, PsA worsened; hence, leflunomide and methotrexate were started. After 4 wk of steroid treatment, PsA worsened and improved repeatedly with steroid tapering. Therefore, the therapy was intensified to include etanercept, a tumor necrosis factor inhibitor, which ultimately resulted in adequate PsA control. CONCLUSION: This is the first report of ICI-induced PsA in a gastric cancer patient. Some rheumatic irAEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Clinical Outcomes of Patients with Benign Peptic Ulcer Bleeding After an Emergency Endoscopy Based on Patient Location.

BACKGROUND AND AIMS: In the efforts toward reducing bleeding-related mortality, it is crucial to determine the risk factors for rebleeding after endoscopic hemostasis in benign peptic ulcer (BPU). METHODS: Between 2013 and 2017, the medical records of 864 BPU patients were selected from 5076 who had undergone emergency endoscopy for suspected upper gastrointestinal bleeding. Patients who visited the emergency room or were hospitalized for other illnesses were selected. The primary end point was rebleeding within 30 days after initial endoscopy. The risk factors of rebleeding and subgroup analyses according to patient location were evaluated. RESULTS: Among 864 BPU bleeding patients, rebleeding after completion of BPU bleeding occurred in 140 (16.2%). Initial indicators of hypotension (OR 1.878, p = 0.005) and Forrest classes Ia (OR 25.53, p < 0.001), Ib (OR 27.91, p = 0.005), IIa (OR 21.41, p < 0.001), and IIb (OR 23.74, p < 0.001) were independent risk factors of rebleeding compared to Forrest class III, and being inpatients (OR 1.75, p = 0.01). Compared to the outpatients, the inpatients showed significantly higher rebleeding rates (25.6% vs 13.8%, p < 0.001), predictive bleeding scores, red blood transfusion counts, proportion of Forrest classes Ia, Ib, and IIb (p < 0.001), and overall mortality rates (68.8% vs 34.0%, p < 0.001). CONCLUSIONS: Patient location was a novel predictive factor of BPU rebleeding. Particularly, being an inpatient correlated with increased rebleeding. Furthermore, Forrest classes Ia, Ib, IIa, and IIb were predictive of rebleeding not only the included BPUs, but also in the inpatient or outpatient groups.

Incidence of acute cholecystitis underwent cholecystectomy in incidence dialysis patients: a nationwide population-based cohort study in Korea.

BACKGROUND: Patients on dialysis have numerous gastrointestinal problems related to uremia, which may represent concealed cholecystitis. We investigated the incidence and risk of acute cholecystitis in dialysis patients and used national health insurance data to identify acute cholecystitis in Korea. METHODS: The Korean National Health Insurance Database was used, with excerpted data from the insurance claim of the International Classification of Diseases code of dialysis and acute cholecystitis treated with cholecystectomy. We included all patients who commenced dialysis between 2004 and 2013 and selected the same number of controls via propensity score matching. RESULTS: A total of 59,999 dialysis and control patients were analyzed; of these, 3,940 dialysis patients (6.6%) and 647 controls (1.1%) developed acute cholecystitis. The overall incidence of acute cholecystitis was 8.04-fold higher in dialysis patients than in controls (95% confidence interval, 7.40-8.76). The acute cholecystitis incidence rate (incidence rate ratio, 23.13) was especially high in the oldest group of dialysis patients (aged ≥80 years) compared with that of controls. Dialysis was a significant risk factor for acute cholecystitis (adjusted hazard ratio, 8.94; 95% confidence interval, 8.19-9.76). Acute cholecystitis developed in 3,558 of 54,103 hemodialysis patients (6.6%) and in 382 of 5,896 patients (6.5%) undergoing peritoneal dialysis. CONCLUSION: Patients undergoing dialysis had a higher incidence and risk of acute cholecystitis than the general population. The possibility of a gallbladder disorder developing in patients with gastrointestinal problems should be considered in the dialysis clinic.

Comparison of LiTaO3 and LiNbO3 Surface Layers Prepared by Post- and Precursor-Based Coating Methods for Ni-Rich Cathodes of All-Solid-State Batteries.

Surface coating is essential for the cathode materials applied in all-solid-state batteries (ASSBs) based on sulfide electrolytes because of the instability of the cathode/sulfide interface. In contrast with those for general lithium ion batteries (LIBs) using a liquid electrolyte, the coating materials for ASSBs require different functional properties such as high ionic conductivity, low reactivity with sulfide electrolytes, and low electronic conductivity. In addition to LiNbO3, which is the most popular coating material for ASSBs, LiTaO3 is another highly promising coating material, and both materials mostly satisfy these requirements. In this work, LiTaO3 and LiNbO3 were used to coat the surface of LiNi0.82Co0.12Mn0.06O2 cathodes for ASSBs. Further, the effects of two different coating methods, postcoating and precursor-based (PB) coating, were characterized and compared. The postcoating method simply forms a coating layer, whereas the PB coating method offers an additional doping effect owing to the diffusion of coating ions into the cathode structure. Surface coating considerably increased the capacity of the ASSB cathodes under all experimental conditions. With the same coating amount and method, the effect of the LiTaO3 coating was similar or superior to that of the LiNbO3 coating. Compared with the postcoating method, however, the PB coating method resulted in a superior rate capability and cyclic performance, which was mostly attributed to the doping effect of Ta or Nb. An X-ray photoelectron spectroscopy analysis confirmed that both the LiTaO3 and LiNbO3 coatings suppressed side reactions. Among the coatings we examined, the LiTaO3 coating prepared by the PB method most effectively enhanced the electrochemical performance of the cathodes for sulfide electrolyte-based ASSBs.

[Inflammatory Bowel Disease and Vitamin D].

Vitamin D contributes to bone metabolism and acts as an immune modulator for both innate and adaptive immunity. The serum level of vitamin D has been associated with inflammatory diseases, such as inflammatory bowel disease (IBD). In epidemiologic studies, IBD patients have been shown to have low levels of vitamin D. The suboptimal circulating levels of vitamin D in IBD patients may be caused by low exposure to sunlight, dietary malabsorption, and the impaired conversion of active metabolites (1,25[OH]2D). Recent studies have demonstrated that vitamin D deficiency in IBD can increase the chance of disease recurrence, IBD-related hospitalization or surgery, and deterioration of quality of life. Supplementation with vitamin D is therefore thought to reduce the risk of flare-ups and the improvement of the quality of life in IBD patients. This review aims to summarize the latest knowledge on the effects of vitamin D deficiency on IBD and the possible benefits of vitamin D supplementation in IBD patients.

Hierarchically Well-Developed Porous Graphene Nanofibers Comprising N-Doped Graphitic C-Coated Cobalt Oxide Hollow Nanospheres As Anodes for High-Rate Li-Ion Batteries.

Hierarchically well-developed porous graphene nanofibers comprising N-doped graphitic C (NGC)-coated cobalt oxide hollow nanospheres are introduced as anodes for high-rate Li-ion batteries. For this, three strategies, comprising the Kirkendall effect, metal-organic frameworks, and compositing with highly conductive C, are applied to the 1D architecture. In particular, NGC layers are coated on cobalt oxide hollow nanospheres as a primary transport path of electrons followed by graphene-nanonetwork-constituting nanofibers as a continuous and secondary electron transport path. Superior cycling performance is achieved, as the unique nanostructure delivers a discharge capacity of 823 mAh g-1 after 500 cycles at 3.0 A g-1 with a low decay rate of 0.092% per cycle. The rate capability is also noteworthy as the structure exhibits high discharge capacities of 1035, 929, 847, 787, 747, 703, 672, 650, 625, 610, 570, 537, 475, 422, 294, and 222 mAh g-1 at current densities of 0.5, 1.5, 3, 5, 7, 10, 12, 15, 18, 20, 25, 30, 40, 50, 80, and 100 A g-1 , respectively. In view of the highly efficient Li+ ion/electron diffusion and high structural stability, the present nanostructuring strategy has a huge potential in opening new frontiers for high-rate and long-lived stable energy storage systems.

Acoustic Trapping Technique for Studying Calcium Response of a Suspended Breast Cancer Cell: Determination of Its Invasion Potentials.

A noncontact single-beam acoustic trapping technique has proven to be a promising tool for cell manipulation and characterization that provide essential knowledge for a variety of biomedical applications. Here, we investigated cell characteristics as to whether the calcium responses of suspended breast cancer cells to different acoustic trapping forces are related to their invasiveness. For this, we combined a single-beam acoustic trapping system with a 30-MHz press-focused lithium niobate ultrasound transducer and an epifluorescence microscope. Using the system, intracellular calcium changes of suspended MDA-MB-231 (highly invasive) and MCF-7 (weakly invasive) cells were monitored while trapping the cells at different acoustic pressures. The results showed that a single suspended breast cancer cell isolated by the acoustic microbeam behaved differently on the calcium elevation in response to changes in acoustic trapping force, depending on its invasiveness. In particular, the MDA-MB-231 cells exhibited higher calcium elevation than MCF-7 cells when each cell was trapped at low acoustic pressure. Based on these results, we believe that the single-beam acoustic trapping technique has high potential as an alternative tool for determining the degree of invasiveness of suspended breast cancer cells.

RORα controls hepatic lipid homeostasis via negative regulation of PPARγ transcriptional network.

The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD). Global transcriptome analysis reveals that liver-specific deletion of Rorα leads to the dysregulation of PPARγ signaling and increases hepatic glucose and lipid metabolism. RORα specifically binds and recruits histone deacetylase 3 (HDAC3) to PPARγ target promoters for the transcriptional repression of PPARγ. PPARγ antagonism restores metabolic homeostasis in HFD-fed liver-specific Rorα deficient mice. Our data indicate that RORα has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic strategies designed to modulate RORα activity may be beneficial for the treatment of metabolic disorders.Hepatic steatosis development may result from dysregulation of lipid metabolism, which is finely tuned by several transcription factors including the PPAR family. Here Kim et al. show that the nuclear receptor RORα inhibits PPARγ-mediated transcriptional activity by interacting with HDAC3 and competing for the promoters of lipogenic genes.

Liver receptor homolog-1 regulates mouse superoxide dismutase 2.

Liver receptor homolog-1 (LRH-1) is a nuclear receptor that plays an important role in the regulation of bile acid biosynthesis, cholesterol reverse transport, steroidogenesis, and exocrine pancreatic enzyme production. In the current study, previously published data from a genome wide analysis of LRH-1 binding in the liver were re-analyzed to identify new LRH-1 targets and propose new roles for LRH-1 in the liver. Superoxide dismutase 2 (Sod2) was identified, which contains putative LRH-1 binding sites in the proximal promoter. When hepatocytes were treated with the LRH-1 agonist RJW101, Sod2 expression was dramatically increased and reactive oxygen species (ROS) production, which was induced by a high concentration of palmitate, was significantly reduced. A LRH-1 binding site was mapped to -288/-283 in the Sod2 promoter, which increased Sod2 promoter activity in response to LRH-1 and its agonist. LRH-1 binding to this site was confirmed using a chromatin immunoprecipitation assay. These results suggest that Sod2 is a target gene of LRH-1, and that LRH-1 agonists can mediate a reduction in ROS production and oxidative stress driven by an excess of fatty acids, as exhibited in nonalcoholic fatty liver disease.

High Density, High Radiance $\mu$ LED Matrix for Optogenetic Retinal Prostheses and Planar Neural Stimulation.

Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride µ LEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The µLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.

Flip-chip integration of tilted VCSELs onto a silicon photonic integrated circuit.

In this article we describe a cost-effective approach for hybrid laser integration, in which vertical cavity surface emitting lasers (VCSELs) are passively-aligned and flip-chip bonded to a Si photonic integrated circuit (PIC), with a tilt-angle optimized for optical-insertion into standard grating-couplers. A tilt-angle of 10° is achieved by controlling the reflow of the solder ball deposition used for the electrical-contacting and mechanical-bonding of the VCSEL to the PIC. After flip-chip integration, the VCSEL-to-PIC insertion loss is -11.8 dB, indicating an excess coupling penalty of -5.9 dB, compared to Fibre-to-PIC coupling. Finite difference time domain simulations indicate that the penalty arises from the relatively poor match between the VCSEL mode and the grating-coupler.

Fukutin mutations in congenital muscular dystrophies with defective glycosylation of dystroglycan in Korea.

This study was aimed to identify Fukutin (FKTN)-related congenital muscular dystrophies (CMD) with defective alpha-dystroglycan glycosylation in Korea and to discuss their genotype-phenotype spectrum focusing on detailed brain magnetic resonance imaging (MRI) findings. FKTN mutations were found in nine of the 12 CMD patients with defective alpha-dystroglycan glycosylation patients (75%). Two patients were homozygous for the Japanese founder retrotransposal insertion mutation. Seven patients were heterozygous for the retrotransposal insertion mutation, five of whom carried a novel intronic mutation that activates a pseudoexon between exons 5 and 6 (c.647+2084G>T). Compared with individuals that were homozygous for the retrotransposal insertion mutation, the seven heterozygotes for the retrotransposal insertion mutation, including five patients with the novel pseudoexon mutation, exhibited a more severe clinical phenotype in terms of motor abilities and more extensive brain MRI abnormalities (i.e., a wider distribution of cortical malformation and pons and cerebellar hypoplasia). FKTN mutations are the most common genetic cause of CMD with defective alpha-dystroglycan glycosylation in Korea. Compound heterozygosity of the retrotransposal insertion and the novel pseudoexon mutation is the most prevalent genotype in Korea and is associated with a more severe clinical and radiological phenotype compared with homozygosity for the retrotransposal insertion mutation.