Integrated optical frequency division for microwave and mmWave generation.

The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems1-3. Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches4-7. Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator10-12. Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications13.

Preparation and characterization of photosensitive methacrylate-grafted sodium carboxymethyl cellulose as an injectable material to fabricate hydrogels for biomedical applications.

Injectable materials have attracted great attention in the manufacture of in situ forming hydrogels for biomedical applications. In this study, a facile method to prepare methacrylic anhydride (MA)-modified sodium carboxymethyl cellulose (CMC) as an injectable material for the fabrication of hydrogels with controllable properties is reported. The chemical structure of the series of MA-grafted CMC (CMCMAs) with different MA contents was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopy, and the properties of CMCMAs were characterized. Then, the CMCMAs gel (CMCMAs-G) was fabricated by crosslinking of MA under blue light irradiation. The gelation performances, swelling behaviors, transmittance, surface porous structures and mechanical properties of CMCMAs-G can be controlled by varying the content of MA grafted on the CMC. The compressive strength of CMCMAs-G was measured by mechanical compressibility tests and up to 180 kPa. Furthermore, the in vitro cytocompatibility evaluation results suggest that the obtained CMCMAs-G exhibit good compatibility for cell proliferation. Hence, our strategy provides a facile approach for the preparation of light-sensitive and an injectable CMC-derived polymer to fabricate hydrogels for biomedical applications.

[Application of gelatin microspheres in bone tissue engineering].

Gelatin microspheres were discussed as a scaffold material for bone tissue engineering, with the advantages of its porosity, biodegradability, biocompatibility, and biosafety highlighted. This review discusses how bone regeneration is aided by the three fundamental components of bone tissue engineering-seed cells, bioactive substances, and scaffold materials-and how gelatin microspheres can be employed for in vitro seed cell cultivation to ensure efficient expansion. This review also points out that gelatin microspheres are advantageous as drug delivery systems because of their multifunctional nature, which slows drug release and improves overall effectiveness. Although gelatin microspheres are useful for bone tissue creation, the scaffolds that take into account their porous structure and mechanical characteristics might be difficult to be created. This review then discusses typical techniques for creating gelatin microspheres, their recent application in bone tissue engineering, as well as possible future research directions.

Cervical collar use following anterior cervical hybrid surgery: protocol for a prospective randomized, time-controlled trial.

INTRODUCTION: Cervical hybrid surgery (HS) combines anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) to establish an individualized surgical plan for patients with multiple cervical disc degenerative diseases. In order to maintain the stability of the spine after HS, an external cervical collar is often used. However, there is still controversy regarding the importance of a cervical collar following surgery. This study aims to determine whether the cervical collar is effective and how long it should be worn after surgery. METHODS: This is a randomized, single-center, prospective, parallel-controlled trial. Eligible participants will be selected according to the inclusion and exclusion criteria. The primary outcome is the neck disability index, which will be evaluated before surgery and at one week, 3 weeks, 6 weeks, 3 months, 6 months, and 12 months following surgery. The secondary outcomes consist of the Japanese Orthopedic Association Scores, MOS 36-item short-form health survey (SF-36), visual analog scale, Pittsburgh Sleep Quality Index (PSQI), Bazaz dysphagia scoring system, Falls Efficacy Scale, cervical collar satisfaction score, neck soft tissue assessment, and Braden Scale, as well as radiologic assessments for cervical lordosis, disc height of the operative levels, fusion rate, range of motion (ROM), and complications including anterior bone loss, prosthesis migration, and heterotopic ossification. The clinical and radiologic examinations were performed by investigators with no therapeutic relationship with the individual patient. All radiographs were examined by one independent radiologist. ETHICS AND DISSEMINATION: The results of this study will be published in peer-reviewed journals and presented at conferences. Upon completion of this trial, our findings could provide an appropriate cervical collar-wearing guideline for patients receiving HS. TRIAL REGISTRATION: ChiCTR.org.cn ChiCTR2000033002. Registered on 2020-05-17.

Efficacy and safety comparison of neoadjuvant chemotherapy followed by surgery and upfront surgery for treating intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Currently, surgical resection is the most commonly performed and effective treatment for intrahepatic cholangiocarcinoma (ICC) worldwide. However, the prognosis of ICC is unsatisfactory. This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery and upfront surgery in treating intrahepatic cholangiocarcinoma (ICC). The study also intends to explore whether chemotherapy should be introduced before surgery and which populations should be considered for neoadjuvant chemotherapy. METHOD: Four databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched from their inception dates to January 2022 for relevant articles. The statistical analysis was performed using the Review Manager Software (version5.3). The non-randomized interventions (ROBINS-I) was used to assess the methodological quality of included studies and the overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Moreover, the primary outcomes included 1-year, 3-year and 5-year overall survival (OS), while the secondary outcomes were R0 resection, 1-year, 3-year and 5-year recurrence-free survival (RFS), postoperative complications and ninety-day postoperative mortality. RESULTS: Five studies involving 2412 patients were included in this meta-analysis. There was no significant difference in 1-year OS, 3-year OS, 1-year, 3-year and 5-year RFS, postoperative complications and ninety-day postoperative mortality between the two groups. However, the meta-analysis showed that the neoadjuvant chemotherapy group had a better 5-year OS benefit in ICC patients than the upfront surgery group (OR = 1.27, 95% CI: 1.02-1.58), while the R0 resection rate was lower in neoadjuvant chemotherapy group than that in the upfront surgery group (OR = 0.49, 95% CI: 0.26-0.91). CONCLUSION: Compared with the upfront surgery, neoadjuvant chemotherapy followed by surgery could prolong the 5-year OS without increasing the risk of postoperative complications in ICC patients. Considering that the patients in the neoadjuvant chemotherapy followed by surgery group had more advanced ICC cases, the benefits of neoadjuvant chemotherapy may be more significant in patients with more advanced ICC.

Effect of MBSR, DBT and CBT on the hypertension patients with depression/anxiety: Protocol of a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Hypertension, one of the most common chronic diseases worldwide, usually requires lifetime managing blood pressure (BP) with medications. Due to quite large number of hypertension patients co-exist with depression and/or anxiety, and non-cooperated with medical instruction, consequently management of BP is impaired with serious complications, resulting in compromised quality of life. Consequently quality of life of such patients is impaired with serious complications. Therefore, management of depression and/or anxiety is equally important as the treatment of hypertension. Depression and/or anxiety are independent risk factors of hypertension, which is supported by the finding that there is close correlation between hypertension are depression/or anxiety. Psychotherapy (non-drug treatment) maybe useful for hypertensive patients with depression and/or anxiety to improve their negative emotions. We aim to quantify the effective of psychological therapies in the management of hypertension patients with depression or anxiety, by comparing and ranking a network meta-analysis (NMA). MATERIALS AND METHODS: Literature search for randomized controlled trials (RCTs) will be performed in five electronic databases from inception to December 2021, including PubMed, the Cochrane library, Embase, Web of Science, and China Biology Medicine disc (CBM). The search terms mainly include "hypertension", "mindfulness-based stress reduction" (MBSR), "cognitive behavioral therapy" (CBT) and "dialectical behavior therapy" (DBT). Cochrane Collaboration quality assessment tool will be used for the risk of bias assessment. A Bayesian network meta-analysis will be performed, using WinBUGS 1.4.3, and Stata 14 will be applied to draw the network diagram, while RevMan 5.3.5 will be used to produce funnel plot for assessing the risk of publication bias. Recommended rating, development and grade methodology will also be utilized to assess the quality of evidence. RESULTS: Effect of MBSR, CBT and DBT will be evaluated by traditional meta-analysis directly and Bayesian network meta-analysis indirectly. Our study will provide the evidence on the efficacy and safety of psychological treatments in the hypertension patients with anxiety. There is no research ethical requirement because this is a systematic review of published literature. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Prospero registration number: CRD42021248566.

A squeezed quantum microcomb on a chip.

The optical microresonator-based frequency comb (microcomb) provides a versatile platform for nonlinear physics studies and has wide applications ranging from metrology to spectroscopy. The deterministic quantum regime is an unexplored aspect of microcombs, in which unconditional entanglements among hundreds of equidistant frequency modes can serve as critical ingredients to scalable universal quantum computing and quantum networking. Here, we demonstrate a deterministic quantum microcomb in a silica microresonator on a silicon chip. 40 continuous-variable quantum modes, in the form of 20 simultaneously two-mode squeezed comb pairs, are observed within 1 THz optical span at telecommunication wavelengths. A maximum raw squeezing of 1.6 dB is attained. A high-resolution spectroscopy measurement is developed to characterize the frequency equidistance of quantum microcombs. Our demonstration offers the possibility to leverage deterministically generated, frequency multiplexed quantum states and integrated photonics to open up new avenues in fields of spectroscopy, quantum metrology, and scalable, continuous-variable-based quantum information processing.

Towards high-power, high-coherence, integrated photonic mmWave platform with microcavity solitons.

Millimetre-wave (mmWave) technology continues to draw great interest due to its broad applications in wireless communications, radar, and spectroscopy. Compared to pure electronic solutions, photonic-based mmWave generation provides wide bandwidth, low power dissipation, and remoting through low-loss fibres. However, at high frequencies, two major challenges exist for the photonic system: the power roll-off of the photodiode, and the large signal linewidth derived directly from the lasers. Here, we demonstrate a new photonic mmWave platform combining integrated microresonator solitons and high-speed photodiodes to address the challenges in both power and coherence. The solitons, being inherently mode-locked, are measured to provide 5.8 dB additional gain through constructive interference among mmWave beatnotes, and the absolute mmWave power approaches the theoretical limit of conventional heterodyne detection at 100 GHz. In our free-running system, the soliton is capable of reducing the mmWave linewidth by two orders of magnitude from that of the pump laser. Our work leverages microresonator solitons and high-speed modified uni-traveling carrier photodiodes to provide a viable path to chip-scale, high-power, low-noise, high-frequency sources for mmWave applications.

Vernier frequency division with dual-microresonator solitons.

Microresonator solitons are critical to miniaturize optical frequency combs to chip scale and have the potential to revolutionize spectroscopy, metrology and timing. With the reduction of resonator diameter, high repetition rates up to 1 THz become possible, and they are advantageous to wavelength multiplexing, coherent sampling, and self-referencing. However, the detection of comb repetition rate, the precursor to all comb-based applications, becomes challenging at these repetition rates due to the limited bandwidth of photodiodes and electronics. Here, we report a dual-comb Vernier frequency division method to vastly reduce the required electrical bandwidth. Free-running 216 GHz "Vernier" solitons sample and divide the main soliton's repetition frequency from 197 GHz to 995 MHz through electrical processing of a pair of low frequency dual-comb beat notes. Our demonstration relaxes the instrumentation requirement for microcomb repetition rate detection, and could be applied for optical clocks, optical frequency division, and microwave photonics.

An improved similarity-based approach to predicting and mapping soil organic carbon and soil total nitrogen in a coastal region of northeastern China.

Soil organic carbon (SOC) and soil total nitrogen (STN) are major soil indicators for soil quality and fertility. Accurate mapping SOC and STN in soils would help both managed and natural soils and ecosystem management. This study developed an improved similarity-based approach (ISA) to predicting and mapping topsoil (0-20 cm soil depth) SOC and STN in a coastal region of northeastern China. Six environmental variables including elevation, slope gradient, topographic wetness index, the mean annual temperature, the mean annual temperature, and normalized difference vegetation index were used as predictors. Soil survey data in 2012 was designed based on the clustering of the study area into six climatic vegetation landscape units. In each landscape unit, 20-25 sampling points were determined at different landform positions considering local climate, soil type, elevation and other environmental factors, and finally 126 sampling points were obtained. Soil sampling from the depth of 0-20 cm were used for model prediction and validation. The ISA model performance was compared with the geographically weighted regression (GWR), regression kriging (RK), boosted regression trees (BRT) considering mean absolute prediction error (MAE), root mean square error (RMSE), coefficient of determination (R 2), and maximum relative difference (RD) indices. We found that the ISA method performed best with the highest R2 and lowest MAE, RMSE compared to GWR, RK, and BRT methods. The ISA method could explain 76% and 83% of the total SOC and STN variability, respectively, 12-40% higher than other models in the study area. Elevation had the largest influence on SOC and STN distribution. We conclude that the developed ISA model is robust and effective in mapping SOC and STN, particularly in the areas with complex vegetation-landscape when limited samples are available. The method needs to be tested for other regions in our future research.

Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

PURPOSE: Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). METHODS: In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. RESULTS: For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). CONCLUSIONS: The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson's Disease.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD. METHODS: The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis. RESULTS: Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results. CONCLUSIONS: When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.