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.

Contribution of protein conformational heterogeneity to NMR lineshapes at cryogenic temperatures.

While low-temperature Nuclear Magnetic Resonance (NMR) holds great promise for the analysis of unstable samples and for sensitizing NMR detection, spectral broadening in frozen protein samples is a common experimental challenge. One hypothesis explaining the additional linewidth is that a variety of conformations are in rapid equilibrium at room temperature and become frozen, creating an inhomogeneous distribution at cryogenic temperatures. Here, we investigate conformational heterogeneity by measuring the backbone torsion angle (Ψ) in Escherichia coli Dihydrofolate Reductase (DHFR) at 105 K. Motivated by the particularly broad N chemical shift distribution in this and other examples, we modified an established NCCN Ψ experiment to correlate the chemical shift of Ni+1 to Ψi. With selective 15N and 13C enrichment of Ile, only the unique I60-I61 pair was expected to be detected in 13C'-15N correlation spectrum. For this unique amide, we detected three different conformation basins based on dispersed chemical shifts. Backbone torsion angles Ψ were determined for each basin: 114 ± 7° for the major peak and 150 ± 8° and 164 ± 16° for the minor peaks as contrasted with 118° for the X-ray crystal structure (and 118° to 130° for various previously reported structures). These studies support the hypothesis that inhomogeneous distributions of protein backbone torsion angles contribute to the lineshape broadening in low-temperature NMR spectra.

Keeping patients safe through medication review and management in the community.

BACKGROUND: There are numerous publications on inpatient medication errors. However, little focus is given to medication errors that occur at home. AIMS: To describe and analyse the types of medication errors among community-dwelling patients following their discharge from an acute care hospital in Singapore. METHOD: This is a retrospective review of a 'good catch' reporting system from December 2018 to March 2022. Medication-related errors were extracted and analysed. FINDINGS: A total of 73 reported medication-related error incidents were reviewed. The mean age of the patients was 78 years old (SD=9). Most patients managed their medications independently at home (45.2%, n=33). The majority of medications involved were cardiovascular medications (51.5%, n=50). Incorrect dosing (41.1%, n=39) was the most common medication error reported. Poor understanding of medication usage (35.6%, n=26) and lack of awareness of medication changes after discharge (24.7%, n=18) were the primary causes of the errors. CONCLUSION: This study's findings provide valuable insights into reducing medication errors at home. More attention must be given to post-discharge care, especially to preventable medication errors. Medication administration and management education can be emphasised using teach-back methods.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Neutrophils as potential therapeutic targets for breast cancer.

Breast cancer (BC) remains the foremost cause of cancer mortality globally, with neutrophils playing a critical role in its pathogenesis. As an essential tumor microenvironment (TME) component, neutrophils are emerging as pivotal factors in BC progression. Growing evidence has proved that neutrophils play a Janus- role in BC by polarizing into the anti-tumor (N1) or pro-tumor (N2) phenotype. Clinical trials are evaluating neutrophil-targeted therapies, including Reparixin (NCT02370238) and Tigatuzumab (NCT01307891); however, their clinical efficacy remains suboptimal. This review summarizes the evidence regarding the close relationship between neutrophils and BC, emphasizing the critical roles of neutrophils in regulating metabolic and immune pathways. Additionally, we summarize the existing therapeutic approaches that target neutrophils, highlighting the challenges, and affirming the rationale for continuing to explore neutrophils as a viable therapeutic target in BC management.

Deep learning enables automatic adult age estimation based on CT reconstruction images of the costal cartilage.

OBJECTIVE: Adult age estimation (AAE) is a challenging task. Deep learning (DL) could be a supportive tool. This study aimed to develop DL models for AAE based on CT images and compare their performance to the manual visual scoring method. METHODS: Chest CT were reconstructed using volume rendering (VR) and maximum intensity projection (MIP) separately. Retrospective data of 2500 patients aged 20.00-69.99 years were obtained. The cohort was split into training (80%) and validation (20%) sets. Additional independent data from 200 patients were used as the test set and external validation set. Different modality DL models were developed accordingly. Comparisons were hierarchically performed by VR versus MIP, single-modality versus multi-modality, and DL versus manual method. Mean absolute error (MAE) was the primary parameter of comparison. RESULTS: A total of 2700 patients (mean age = 45.24 years ± 14.03 [SD]) were evaluated. Of single-modality models, MAEs yielded by VR were lower than MIP. Multi-modality models generally yielded lower MAEs than the optimal single-modality model. The best-performing multi-modality model obtained the lowest MAEs of 3.78 in males and 3.40 in females. On the test set, DL achieved MAEs of 3.78 in males and 3.92 in females, which were far better than the MAEs of 8.90 and 6.42 respectively, for the manual method. For the external validation, MAEs were 6.05 in males and 6.68 in females for DL, and 6.93 and 8.28 for the manual method. CONCLUSIONS: DL demonstrated better performance than the manual method in AAE based on CT reconstruction of the costal cartilage. CLINICAL RELEVANCE STATEMENT: Aging leads to diseases, functional performance deterioration, and both physical and physiological damage over time. Accurate AAE may aid in diagnosing the personalization of aging processes. KEY POINTS: • VR-based DL models outperformed MIP-based models with lower MAEs and higher R2 values. • All multi-modality DL models showed better performance than single-modality models in adult age estimation. • DL models achieved a better performance than expert assessments.

Inhibiting α1-adrenergic receptor signaling pathway ameliorates AD-type pathologies and behavioral deficits in APPswe/PS1 mouse model.

The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer's disease (AD) has rarely been investigated. Clarifying the pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic targets of AD. This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (α1-ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or an equal volume of saline for 6 months. SH-SY5Y cell lines bearing human amyloid precursor protein were treated with terazosin or saline for investigating possible mechanisms. α1-ARs knockdown mice exhibited improved behavioral performances in comparison with control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aß species, compact and total Aß plaques, than control mice. α1-ARs inhibitor terazosin substantially reduced Aß deposition, attenuated downstream pathologies including tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction et al., and rescued behavioral deficits in APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3ß, thus reducing Aß production. This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

Comparison of Medical Dispute Resolution Mechanisms in China and Abroad.

Medical disputes are one of the common problems concerned by the whole world. All countries and regions have established their own medical dispute resolution mechanisms, in accordance with their own national conditions. Medical dispute identification opinions, as one of the important bases for identifying the responsibilities of both doctors and patients, play a pivotal role in the process of dispute settlement. A reasonable medical dispute resolution mechanism and standardized medical dispute identification model can help resolve disputes flexibly and reduce the conflict between doctors and patients. This paper briefly compares the medical dispute resolution mechanism and identification mode of China and several other representative countries (the United States, Britain, France, Germany, Italy, Japan, etc.), and discusses their respective characteristics and shortcomings, to bring some enlightenment to the medical dispute resolution and identification in our country.

Changes in empathy of nurses from 2009 to 2018: A cross-temporal meta-analysis.

The empathy of nurses is associated with self-care and self-compassion, which may enhance the quality of the nurse-patient relationship. Yet, research on the empathy of nursing staff has mostly used cross-sectional designs, which cannot capture the degree of empathy changes over time. To explore changes in empathy among nurses in China from 2009 to 2018. A cross-temporal meta-analysis was used to examine continuous changes in the empathy of nurses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to conduct this cross-temporal meta-analysis of 57 samples of nurses in China who completed the three subscales (perspective-taking, compassionate care, and walking in the patient's shoes) of the Jefferson Scale of Empathy-Health Professionals from 2009 to 2018 (N = 13,825). This meta-analysis was conducted following good scientific practice in every phase, and approval by ethics committees was not required according to the local regulations in China. The findings suggest that the nurses' mean total scores of empathy and perspective-taking on the Jefferson Scale of Empathy-Health Professionals declined significantly over time, but the trend in compassionate care and walking in the patient's shoes was not significant. No significant changes were found in the overall empathy or the three dimensions of empathy of the nurses in the Eastern region across time, whereas a significant decline was found on the total empathy and perspective-taking scores of the nurses in other regions (i.e. the Central and Western regions). The mean total score of empathy and walking in the patient's shoes of the nurses who worked in the intensive care units showed a significant decrease over time. Furthermore, these findings indicate that the empathy of Chinese nurses has decreased steadily over the past 10 years. High levels of empathy can effectively reduce healthcare risks, errors, and disputes among nursing staff and enhance patient satisfaction and well-being.

Crossed cerebellar diaschisis after stroke detected noninvasively by arterial spin-labeling MR imaging.

BACKGROUND: As a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT). RESULTS: 17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829. CONCLUSIONS: CBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.

Community nursing services during the COVID-19 pandemic: the Singapore experience.

Community nurses in Singapore support vulnerable older persons with chronic health condition(s). In the situation of scaled-down community health and social services during the COVID-19 outbreak, the community nursing team adopted measures for pandemic preparedness. This report is to share the Singapore General Hospital community nursing experience, preparation and transforming efforts during the pandemic. Team segregation, active screening and triage before visits and other precautionary measures were executed to minimise the risk of exposure to COVID-19. There was a shift from face-to-face to teleconsultation to meet the requirement of safe social-distancing. Community nursing teams continued to play an active role in supporting older persons during the pandemic, despite the challenges. Moving to the lockdown phase ('circuit breaker'), teleconsultation, virtual meetings and integrated partnerships were essential to ensure healthcare accessibility and continuity of care. The experience gleaned was valuable to advance future community nursing services in the evolving healthcare landscape. Structured teleconsultation and technology advancement are useful to complement the service.

Universal isocontours for dissipative Kerr solitons.

Dissipative Kerr solitons can be generated within an existence region defined on a space of normalized pumping power versus cavity-pump detuning frequency. The contours of constant soliton power and constant pulse width in this region are studied through measurement and simulation. Such isocontours impart structure to the existence region and improve understanding of soliton locking and stabilization methods. As part of the study, dimensionless, closed-form expressions for soliton power and pulse width are developed (including Raman contributions). They provide isocontours in close agreement with those from the full simulation, and, as universal expressions, can simplify the estimation of soliton properties across a wide range of systems.

The Influence of Abdominal and Ectopic Fat Accumulation on Carotid Intima-Media Thickness: A Chongqing Study.

BACKGROUND: To investigate the effects of abdominal obesity (AO) and nonalcoholic fatty liver disease (NAFLD) with or without AO on carotid arteries by determining carotid intima-media thickness (CIMT). METHODS: A total of 2745 Chinese Han adults (aged between 40 and 50 years old) were recruited and divided into 4 groups: (1) NW-no NAFL group: the normal body weight without NAFLD (n = 1888); (2) AO-no NAFL group: AO without NAFLD (n = 259); (3) NW-with NAFL group: NAFLD without AO (n = 93); and (4) AO-with NAFL group: AO with NAFLD (n = 505). The CIMT rate of each group was compared among 4 groups and the regression analysis was further used to correct confounders. RESULTS: We found that the NW-with NAFL group had a significantly higher CIMT rate than the AO-no NAFL group ([.87 ± .31] versus [.72 ± .29] P < .01) and the AO-with NAFL group ([.87 ± .31] versus [.79 ± .26], P < .01). CONCLUSIONS: The ectopic liver fat accumulation may increase the risk of atherosclerosis. Therefore, screening NAFLD in the population with normal weight may be beneficial for the prevention of atherosclerosis at an early stage.

Sudden Death From Ruptured Intracranial Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.

Smothering and manual strangulation are not uncommon in domestic violence against women; however, no report on the combination of mechanical asphyxia and intracranial vascular malformations has been previously published. We report a middle-aged woman who was smothered and manually strangled by her husband and subsequently died from subarachnoid hemorrhage due to ruptured intracranial vascular malformations, rather than direct mechanical asphyxiation. Smothering and manual strangulation are considered provocative conditions for rupture and contributory causes of death. In this case study, we underline the importance of meticulous autopsy in cases of mechanical asphyxia and intracranial hemorrhage. Exclusion of underlying diseases that may have caused or contributed to death is also required, despite serious asphyxiation signs and neck injuries. Postmortem angiography is a valuable complement to autopsy to detect vascular pathology, with good prospects for further development in China.

High-Tech Versus High-Touch: Components of Hospital Costs Vary Widely.

EXECUTIVE SUMMARY: The recent release by the Centers for Medicare & Medicaid Services of hospital charge and payment data to the public has renewed a national dialogue on hospital costs and prices. However, to better understand the driving force of hospital pricing and to develop strategies for controlling expenditures, it is important to understand the underlying costs of providing hospital services. We use Medicare Provider and Analysis Review inpatient claims data and Medicare cost report data for fiscal years 2008 and 2012 to examine variations in the contribution of "high-tech" resources (i.e., technology/medical device-intensive resources) versus "high-touch" resources (i.e., labor-intensive resources) to the total costs of providing two common services, as well as assess how these costs have changed over time. We found that high-tech inputs accounted for a greater proportion of the total costs of surgical service, whereas medical service costs were primarily attributable to high-touch inputs. Although the total costs of services did not change significantly over time, the distribution of high-tech, high-touch, and other costs for each service varied considerably across hospitals. Understanding resource inputs and the varying contribution of these inputs by clinical condition is an important first step in developing effective cost control strategies.

All-Inorganic Perovskite Solar Cells.

The research field on perovskite solar cells (PSCs) is seeing frequent record breaking in the power conversion efficiency (PCE). However, organic-inorganic hybrid halide perovskites and organic additives in common hole-transport materials (HTMs) exhibit poor stability against moisture and heat. Here we report the successful fabrication of all-inorganic PSCs without any labile or expensive organic components. The entire fabrication process can be operated in ambient environment without humidity control (e.g., a glovebox). Even without encapsulation, the all-inorganic PSCs present no performance degradation in humid air (90-95% relative humidity, 25 °C) for over 3 months (2640 h) and can endure extreme temperatures (100 and -22 °C). Moreover, by elimination of expensive HTMs and noble-metal electrodes, the cost was significantly reduced. The highest PCE of the first-generation all-inorganic PSCs reached 6.7%. This study opens the door for next-generation PSCs with long-term stability under harsh conditions, making practical application of PSCs a real possibility.

Theory and measurement of the soliton self-frequency shift and efficiency in optical microcavities.

Dissipative Kerr cavity solitons experience a so-called self-frequency shift (SFS) as a result of Raman interactions. The frequency shift has been observed in several microcavity systems. The Raman process has also been shown numerically to influence the soliton pumping efficiency. Here, a perturbed Lagrangian approach is used to derive simple analytical expressions for the SFS and the soliton efficiency. The predicted dependences of these quantities on soliton pulse width are compared with measurements in a high-Q silica microcavity. The Raman time constant in silica is also inferred. Analytical expressions for the Raman SFS and soliton efficiency greatly simplify the prediction of soliton behavior over a wide range of microcavity platforms.

Active capture and stabilization of temporal solitons in microresonators.

Soliton mode locking and femtosecond pulse generation have recently been demonstrated in high-Q optical microcavities and provide a new way to miniaturize frequency comb systems, as well as create integrated comb systems on a chip. However, triggering the mode-locking process is complicated by a well-known thermal hysteresis that can destabilize the solitons. Moreover, on a longer time scale, thermal drifting of the cavity resonant frequency relative to the pumping frequency causes loss of mode locking. In this Letter, an active feedback method is used both to capture specific soliton states and to stabilize the states indefinitely. The capture and stabilization method provides a reliable way to overcome thermal effects during soliton formation and to excite a desired number of circulating cavity solitons. It is also used to demonstrate a low pumping power of 22 mW for generation of microwave-repetition-rate solitons on a chip.

Theory and measurement of the soliton self-frequency shift and efficiency in optical microcavities: publisher's note.

This note points out two corrections that were omitted from the published version of the article [Opt. Lett.41, 3419 (2016)OPLEDP0146-959210.1364/OL.41.003419].

Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics.

NMR chemical shifts provide a sensitive probe of protein structure and dynamics but remain challenging to predict and interpret. We examine the effect of protein conformational distributions on 15N chemical shifts for dihydrofolate reductase (DHFR), comparing QM/MM predicted shifts with experimental shifts in solution as well as frozen distributions. Representative snapshots from MD trajectories exhibit variation in predicted 15N chemical shifts of up to 25 ppm. The average over the fluctuations is in significantly better agreement with room temperature solution experimental values than the prediction for any single optimal conformations. Meanwhile, solid-state NMR (SSNMR) measurements of frozen solutions at 105 K exhibit broad lines whose widths agree well with the widths of distributions of predicted shifts for samples from the trajectory. The backbone torsion angle ψi-1 varies over 60° on the picosecond time scale, compensated by φi. These fluctuations can explain much of the shift variation.