Lung tumor discrimination by deep neural network model CanDo via DNA methylation in bronchial lavage.

Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing. The Recursive Feature Elimination Cross-Validation and deep neural network algorithm established the CanDo classification model, which incorporated 11 methylation features (including 8 specific to the TBR1 gene), demonstrating a sensitivity of 98.6% and specificity of 97.8%. In contrast, bronchoscopic rapid on-site evaluation (bronchoscopic-ROSE) had lower sensitivity (87.7%) and specificity (80%). Further validation in 33 individuals confirmed CanDo's discriminatory potential, particularly in challenging cases for bronchoscopic-ROSE due to pathological complexity. CanDo serves as a valuable complement to bronchoscopy for the discriminatory diagnosis and stratified management of lung tumors utilizing BWF specimens.

Functional analysis of a novel intronic variant of MCPH1 with autosomal recessive primary microcephaly.

Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1. Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH.

Origin of thermally activated Er3+ emission in GeGaSe films and waveguides.

The origin of the dead or active emission from Er in various Er-doped films has been unclear. Here we took Er-doped GeGaSe as examples and investigated the correlation between the intensity of the photoluminescence (PL) spectra, the content of the activated Er ions, and the intensity of the absorption spectra in the waveguides. We found the linear correlation between the content of Er ions, photoluminescence, and absorption intensity. This provides clear evidence that thermal annealing can promote the conversion of Er metals into Er ions, and such a conversion is essential for practical applications, in which the number of the activated Er ions rather than the nominal Er contents in the materials plays an important role in achieving emission and thus effective optical amplification and lasing.

On-chip Er-doped Ta2O5 waveguide amplifiers with a high internal net gain.

We designed and fabricated a double-layered structure Er3+:Ta2O5 waveguide and investigated its optical amplification performance in C band. The pump laser threshold for zero gain at 1533 nm was 2.5 mW, and the internal net gain was ∼4.63 dB/cm for a lunched pump power of 36.1 mW at 980 nm and signal input power of -30.0 dBm (1 µW). The relationship between the internal gain and the signal input power was also investigated, and a large internal net gain of 10.58 dB/cm was achieved at a signal input power of ∼-47.1 dBm. The results confirm the potentials of the use of Ta2O5 as a host material for optical waveguide amplification.

Supercontinuum generation in As2S3 chalcogenide waveguide pumped by all-fiber structured dual-femtosecond solitons.

Supercontinuum sources with high compactness are essential for applications such as optical sensing, airborne detection and communication systems. In the past decades, the adoption of bulky optical parametric amplifier to pump various chalcogenide glass waveguides are widely reported for on-chip mid-infrared supercontinuum generation, but this usually leads to a large volume of the whole system, and is not practical. Therefore, integrating advanced femtosecond fiber lasers with optical waveguides using nano-fabrication technology are highly desired. However, the scarcity of compact pump sources and the dispersion-matched high-nonlinearity waveguide in short wavelength regions have hindered the advancement of integrated supercontinuum source performances in the near and mid-infrared region. In this study, we demonstrate a broadband supercontinuum source from As2S3 waveguide pumped by a compact dual-femtosecond solitons pulse source. The laser is completely fiber structured, and its wavelength can be readily tuned from 2 to 2.3 µm using Raman soliton self-frequency shift technology in a Tm3+-doped fiber amplifier. Furthermore, the As2S3 waveguide is designed with controllable dispersion and high nonlinearity for a broadband supercontinuum generation. These results will advance the development of on-chip supercontinuum sources based on chalcogenide waveguides.

A simplified mid-infrared anti-resonant chalcogenide fiber with fewest resonant peaks.

High-power laser delivery in the mid-infrared via hollow-core fibers is attractive, but it is too difficult to be fabricated using chalcogenide glasses. Here, we designed a mid-infrared hollow-core anti-resonant chalcogenide fiber (HC-ARCF) with a simplified Kagome cladding micro-structure for the first time. Then, the fiber was firstly fabricated through a precision mechanical drilling and pressured fiber drawing method. Ultra-thin walls of 2µm in the fiber lead to the fewest resonance peaks in the 2-5µm among all reported HC-ARCFs. All the fundamental mode, the second-order mode, tube mode and node mode in the fiber were excited and observed at 1550 nm. The power and spectral properties of the core and cladding of HC-ARCF are studied for the first time. The fiber can deliver high-power of 4.84 W without damage with core-coupling, while the threshold of the node in the cladding is only 3.5 W. A broadening of the output spectrum from 1.96 to 2.41µm due to the high nonlinearity at the node was successfully observed under short-pulse laser pumping at 2µm. The potentials of the fiber used for mid-infrared high-power laser delivery via core, or nonlinear laser generation via node, were thus demonstrated.

High-Q chalcogenide racetrack resonators based on the multimode waveguide.

We propose and demonstrate a high quality (Q) factor racetrack resonator based on uniform multimode waveguides in high-index contrast chalcogenide glass film. Our design features two carefully designed multimode waveguide bends based on modified Euler curves, which enable a compact 180° bend and reduce the chip footprint. A multimode straight waveguide directional coupler is utilized to couple the fundamental mode without exciting higher-order modes in the racetrack. The fabricated micro-racetrack resonator shows a record-high intrinsic Q of 1.31×106 for selenide-based devices, with a relatively low waveguide propagation loss of only 0.38 dB/cm. Our proposed design has potential applications in power-efficient nonlinear photonics.

Alterations in regional homogeneity and functional connectivity associated with cognitive impairment in patients with hypertension: a resting-state functional magnetic resonance imaging study.

Our study aims to investigate the alterations and diagnostic efficiency of regional homogeneity (ReHo) and functional connectivity (FC) in hypertension patients with cognitive impairment. A total of 62 hypertension patients with cognitive impairment (HTN-CI), 59 hypertension patients with normal cognition (HTN-NC), and 58 healthy controls (HCs) with rs-fMRI data were enrolled in this study. Univariate analysis (based on whole-brain ReHo and seed-based FC maps) was performed to observe brain regions with significant differences among the three groups. Multiple voxel pattern analysis (MVPA) was applied to evaluate the diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. Compared with the HCs and HTN-NC, HTN-CI exhibited decreased ReHo in the right caudate, left postcentral gyrus, posterior cingulate gyrus, insula, while increased ReHo in the left superior occipital gyrus and superior parietal gyrus. HTN-CI showed increased FC between seed regions (left posterior cingulate gyrus, insula, postcentral gyrus) with many specific brain regions. MVPA analysis (based on whole-brain ReHo and seed-based FC maps) displayed high classification ability in distinguishing HTN-CI from HTN-NC and HCs. The ReHo values (right caudate) and the FC values (left postcentral gyrus seed to left posterior cingulate gyrus) were positively correlated with the MoCA scores in HTN-CI. HTN-CI was associated with decreased ReHo and increased FC mainly in the left posterior cingulate gyrus, postcentral gyrus, insula compared to HTN-NC and HC. Besides, MVPA analysis yields excellent diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. The findings may contribute to unveiling the underlying neuropathological mechanism of HTN-CI.

Disrupted topological organization of functional brain networks is associated with cognitive impairment in hypertension patients: a resting-state fMRI study.

PURPOSE: To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores. METHODS: Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized. RESULTS: HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network. CONCLUSION: This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.

Design and fabrication of large-mode-area multicore chalcogenide fiber with low bending loss.

Multicore fiber (MCF) has a larger mode-area (LMA) compared to traditional single-core fiber, making it easy to get a mode area of more than 3000 µm2 with an optimized MCF structure. Here, a fine-structured 19-core fiber based on chalcogenide glass was fabricated using a combined method involving extrusion, drilling, and rod-in-tube for the first time. The fiber has a minimum transmission loss of 1.8 dB/m at 6.7 µm. When the bending radius exceeds 6 cm, a low bending loss of about 0.6 dB appears, and the experimental data are in good agreement with the simulation results. In addition, the supermode characteristics of the 19-core fiber are analyzed from both perspectives of simulation and experiment, and these results are perfectly in good agreement. We believe it opens a new way to develop high-power and bend-resisting fiber with such kind of multicore structure.

Se-H-free As2Se3 fiber and its spectral applications in the mid-infrared.

The complete removal of the impurities like Se-H in Se-based chalcogenide glasses has been challenging in the development of highly transparent chalcogenide glass fiber. In this paper, several purification methods, including dynamic distillation, static distillation, and combined distillation method, were adopted with an aim of purifying arsenic selenide glass with ultra-low content of the impurities. The experimental results demonstrated that the Se-H can be completely eliminated in the arsenic selenide glass host and fiber without the introduction of any chloride. We further explored the applications of such low loss and Se-H-free chalcogenide glass fiber in the mid-infrared. It was found that, using such a Se-H free fiber, a flattened supercontinuum spectrum above the -30 dB level from 1.2 to 13 µm was generated from the Se-H free fiber with a 5.5 µm laser pumping. The sensitivity was found to be improved 5.1 times for CO2 gas in the 3 to 6 µm wavelength range.

Single-mode suspended large-core chalcohalide fiber with a low zero-dispersion wavelength for supercontinuum generation.

Chalcogenide glass possesses outstanding advantages, such as supercontinuum generation, but its nonlinear applications were limited by large zero-dispersion wavelength (ZDW). Traditional suspended-core fibers can shift the ZDW to near IR with a tiny core size of less than 5 µm but a large evanescent wave loss exists in these fibers. In this paper, we prepared a novel suspended-core fiber (SCF) based on chalcohalide glasses for the first time via the extrusion method, in which the ZDW of the fundamental mode in the fiber with a core size of larger than 30 µm was successfully shifted to 2.6 µm. We also calculated confinement loss (CL) of propagation modes and fundamental mode energy ratio in the fiber. We found that the minimum CL ratio of the high order modes (LP11) to the CL of the fundamental mode is 124, indicating that the single-mode operation condition is satisfied when the wavelength is more than 4.6 µm. The lowest transmission loss is 1.2 dB/m at 6.5 µm. An ultra-broad supercontinuum spectrum, covering from 1.6 to 12 µm was generated in this suspended-core fiber pumped by a 5 µm femtosecond laser. Such a wide SC in the chalcogenide SCF is due to the large core size. All these results demonstrate the potential to use the large core SCF in the application of a mid-IR laser.

Real-time change of optical losses in chalcogenide waveguides induced by light illumination.

We prepared several GeGaSe waveguides with different chemical compositions and measured the change of optical losses induced by light illumination. Together with some experimental data in As2S3 and GeAsSe waveguides, the results showed that maximum change of the optical loss can be observed in the waveguides under bandgap light illumination. The chalcogenide waveguides with close to stoichiometric compositions have less homopolar bonds and less sub-bandgap states, and thus are preferential to have less photoinduced losses.

High-Q, submicron-confined chalcogenide microring resonators.

We demonstrate high quality (Q) factor microring resonators in high index-contrast GeSbSe chalcogenide glass waveguides using electron-beam lithography followed by plasma dry etching. A microring resonator with a radius of 90 µm shows an intrinsic Q factor of 4.1 × 105 in the telecom band. Thanks to the submicron waveguide dimension, the effective nonlinear coefficient was determined to be up to ∼110 W-1m-1 at 1550 nm, yielding a larger figure-of-merit compared with previously reported submicron chalcogenide waveguides. Such a high Q factor, combined with the large nonlinear coefficient and high confinement, shows the great potential of the GeSbSe microring resonator as a competitive platform in integrated nonlinear photonics.

High quality, high index-contrast chalcogenide microdisk resonators.

We demonstrate the high quality (Q) factor microdisk resonators in high index-contrast chalcogenide glass (ChG) film GeSbSe using electron-beam lithography followed by plasma dry etching. High confinement, low-loss, and single-point-coupled microdisk resonators with a loaded Q factor of 5×105 are measured. We also present pulley-coupled microdisk resonators for relaxing the requirements on the coupling gap. While adjusting the wrap-around coupling waveguides to be phase-matched to the resonator mode, a single specific microdisk radial mode can be excited. Moreover, the thermal characterization of microdisk resonators is carried out to estimate the thermo-optic coefficient of 6.7×10-5/K for bulk ChG.

Micro-Structure Changes Caused by Thermal Evolution in Chalcogenide GexAsySe1-x-y Thin Films by In Situ Measurements.

To understand the effects of thermal annealing on the structure of GexAsySe1-x-y thin films, the thermal evolution of these films was measured by the in situ X-ray diffraction (XRD) at different temperature (773 K or 1073 K) in a vacuum (10-1 Pa) environment. The entire process of crystallization can be observed by using in situ XRD, which is from the appearance of a crystal structure to melting liquid-state and ultimately to the disappearance of the amorphous structure. In the crystallized process, the corresponding state-transition temperatures Tx (the onset crystallization temperature), Tl (the transition temperature from glassy-state to liquid-state), Tp (peak crystallization temperature) are linear with MCN (Mean Coordination Number). In order to obtain information about changes in the amorphous structural origin of the anneal-induced material, the samples were analyzed by in situ Raman spectroscopy. Analysis of the results through decomposing the Raman spectra into different structural units showed that the Ge-Ge, As-As, or Se-Se homopolar bonds as the nonequilibrium minority carriers could be found in films. It suggests that the formation of these bonds cannot be completely suppressed in any case, as one falls and another rises.

Bilateral striatum with high-signal intensity on T1-weighted MRI: A case of hemichorea induced by nonketotic hyperglycemia.

Hemichorea induced by nonketotic hyperglycemia is a rare complication of diabetes mellitus. Here we present a case of 80-year-old female patient. She had a history of involuntary movement of the left body. Imaging examination showed abnormal signs of bilateral basal ganglia. After relevant treatment was conducted, the patient's hemichorea symptoms were significantly improved. Imaging features of nonketotic hyperglycemia Hemichorea plays a very important role in diagnosing and treatment of this disease. Introduction: Hemichorea refers to the involuntary movements of one or more limbs of the same side. These movements are continuous and irregular, variable amplitude, and usually involve the arms and legs together. Stroke is the most common reason, hyperglycemia is relatively rare. Characteristic imaging findings can be very suggestive of diagnosis, and also closely related to the development of disease. Here we present a case of hemichorea induced by nonketotic hyperglycemia which was confirmed by bilateral abnormal signals of basal ganglia in MRI.

Preoperative CT Radiomics Predicting the SSIGN Risk Groups in Patients With Clear Cell Renal Cell Carcinoma: Development and Multicenter Validation.

Objective: The stage, size, grade, and necrosis (SSIGN) score can facilitate the assessment of tumor aggressiveness and the personal management for patients with clear cell renal cell carcinoma (ccRCC). However, this score is only available after the postoperative pathological evaluation. The aim of this study was to develop and validate a CT radiomic signature for the preoperative prediction of SSIGN risk groups in patients with ccRCC in multicenters. Methods: In total, 330 patients with ccRCC from three centers were classified into the training, external validation 1, and external validation 2 cohorts. Through consistent analysis and the least absolute shrinkage and selection operator, a radiomic signature was developed to predict the SSIGN low-risk group (scores 0-3) and intermediate- to high-risk group (score ≥ 4). An image feature model was developed according to the independent image features, and a fusion model was constructed integrating the radiomic signature and the independent image features. Furthermore, the predictive performance of the above models for the SSIGN risk groups was evaluated with regard to their discrimination, calibration, and clinical usefulness. Results: A radiomic signature consisting of sixteen relevant features from the nephrographic phase CT images achieved a good calibration (all Hosmer-Lemeshow p > 0.05) and favorable prediction efficacy in the training cohort [area under the curve (AUC): 0.940, 95% confidence interval (CI): 0.884-0.973] and in the external validation cohorts (AUC: 0.876, 95% CI: 0.811-0.942; AUC: 0.928, 95% CI: 0.844-0.975, respectively). The radiomic signature performed better than the image feature model constructed by intra-tumoral vessels (all p < 0.05) and showed similar performance with the fusion model integrating radiomic signature and intra-tumoral vessels (all p > 0.05) in terms of the discrimination in all cohorts. Moreover, the decision curve analysis verified the clinical utility of the radiomic signature in both external cohorts. Conclusion: Radiomic signature could be used as a promising non-invasive tool to predict SSIGN risk groups and to facilitate preoperative clinical decision-making for patients with ccRCC.

A Computed Tomography-Based Radiomics Nomogram to Preoperatively Predict Tumor Necrosis in Patients With Clear Cell Renal Cell Carcinoma.

Objective: To develop and validate a radiomics nomogram for preoperative prediction of tumor necrosis in patients with clear cell renal cell carcinoma (ccRCC). Methods: In total, 132 patients with pathologically confirmed ccRCC in one hospital were enrolled as a training cohort, while 123 ccRCC patients from second hospital served as the independent validation cohort. Radiomic features were extracted from corticomedullary and nephrographic phase contrast-enhanced computed tomography (CT) images. A radiomics signature based on optimal features selected by consistency analysis and the least absolute shrinkage and selection operator was developed. An image features model was constructed based on independent image features according to visual assessment. By integrating the radiomics signature and independent image features, a radiomics nomograph was constructed. The predictive performance of the above models was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, the nomogram was assessed using calibration curve and decision curve analysis. Results: Thirty-seven features were used to establish a radiomics signature, which demonstrated better predictive performance than did the image features model constructed using tumor size and intratumoral vessels in the training and validation cohorts (p <0.05). The radiomics nomogram demonstrated satisfactory discrimination in the training (area under the ROC curve [AUC] 0.93 [95% CI 0.87-0.96]) and validation (AUC 0.87 [95% CI 0.79-0.93]) cohorts and good calibration (Hosmer-Lemeshow p>0.05). Decision curve analysis verified that the radiomics nomogram had the best clinical utility compared with the other models. Conclusion: The radiomics nomogram developed in the present study is a promising tool to predict tumor necrosis and facilitate preoperative clinical decision-making for patients with ccRCC.

Design and fabrication of As2Se3 chalcogenide waveguides with low optical losses.

In this paper, we report the fabrication and characterization of chalcogenide-based planar waveguides for possible applications in broadband light sources and/or biochemical sensing. ${{\rm Ge}_{11.5}}{{\rm As}_{24}}{{\rm Se}_{64.5}}$Ge11.5As24Se64.5 film as bottom cladding followed by another layer of ${{\rm As}_2}{{\rm Se}_3}$As2Se3 was deposited on a thermally oxidized silicon wafer using thermal evaporation, and the waveguides were patterned directly on the ${{\rm As}_2}{{\rm Se}_3}$As2Se3 layer by UV exposure followed by inductively coupled plasma dry etching. The device structure was optimized by using commercial software (COMSOL Multiphysics) based on complete vector finite components, and the fundamental mode of the waveguide was calculated. By optimizing the geometry of the waveguide, the zero dispersion wavelength was shifted to a short wavelength (at $\sim{2}.{3}\;\unicode{x00B5} {\rm m}$∼2.3µm), which facilitates supercontinuum generation with shorter wavelength pump source. The insertion loss of the rib waveguides with different widths was measured using the cut-back method, and the best propagation loss at 1550 nm was 1.4 dB/cm.