Population Pharmacokinetics of Nirmatrelvir in Chinese Patients with COVID-19: Therapeutic Drug Monitoring and Dosing Regimen Selection in Clinical Practice.

OBJECTIVES: To establish a population pharmacokinetics (PopPK) model of nirmatrelvir in Chinese COVID-19 patients and provide reference for refining the dosing strategy of nirmatrelvir in patients confirmed to be infected with SARS-CoV-2. METHODS: A total of 80 blood samples were obtained from 35 mild moderate COVID-19 patients who were orally administered nirmatrelvir/ritonavir tablets. The PopPK model of nirmatrelvir was developed using a nonlinear mixed effects modeling approach. The stability and prediction of the final model were assessed through a combination of goodness-of-fit and bootstrap method. The exposure of nirmatrelvir across various clinical scenarios was simulated using Monte Carlo simulations. RESULTS: The pharmacokinetics of nirmatrelvir were well characterized by a one-compartment model with first-order absorption, and with creatinine clearance (Ccr) as the significant covariate. Typical population parameter estimates of apparent clearance and distribution volume for a patient with a Ccr of 95.5 mL·min-1were 3.45 L·h-1 and 48.71 L, respectively. The bootstrap and visual predictive check procedures demonstrated satisfactory predictive performance and robustness of the final model. CONCLUSION: The final model was capable of offering an early prediction of drug concentration ranges for different nirmatrelvir dosing regimens and optimize the dose regimen of nirmatrelvir in individuals with confirmed SARS-CoV-2 infection.

Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.

Single cell transcriptome profiling of infrapatellar fat pad highlights the role of interstitial inflammatory fibroblasts in osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a whole-joint disease in which the role of the infrapatellar fat pad (IFP) in its pathogenesis is unclear. Our study explored the cellular heterogeneity of IFP to understand OA and identify therapeutic targets. METHODS: Single-cell and single-nuclei RNA sequencing were used to analyze 10 IFP samples, comprising 5 from OA patients and 5 from healthy controls. Analyses included differential gene expression, enrichment, pseudotime trajectory, and cellular communication, along with comparative studies with visceral and subcutaneous fats. Key subcluster and pathways were validated using multiplex immunohistochemistry. RESULTS: The scRNA-seq performed on the IFPs of the OA and control group profiled the gene expressions of over 49,674 cells belonging to 11 major cell types. We discovered that adipose stem and progenitor cells (ASPCs), contributing to the formation of both adipocytes and synovial-lining fibroblasts (SLF). Interstitial inflammatory fibroblasts (iiFBs) were a subcluster of ASPCs that exhibit notable pro-inflammatory and proliferative characteristics. We identified four adipocyte subtypes, with one subtype showing a reduced lipid synthesis ability. Furthermore, iiFBs modulated the activities of macrophages and T cells in the IFP. Compared to subcutaneous and visceral adipose tissues, iiFBs represented a distinctive subpopulation of ASPCs in IFP that regulated cartilage proliferation through the MK pathway. CONCLUSION: This study presents a comprehensive single-cell transcriptomic atlas of IFP, uncovering its complex cellular landscape and potential impact on OA progression. Our findings highlight the role of iiFBs in OA, especially through MK pathway, opening new avenues for understanding OA pathogenesis and developing novel targeted therapies.

Sensitive, Robust, Wide-Range, and High-Consistency Capacitive Tactile Sensors with Ordered Porous Dielectric Microstructures.

Flexible capacitive tactile sensors show great promise in personalized healthcare monitoring and human-machine interfaces, but their practical application is normally hindered because they rarely possess the required comprehensive performance, that is, high pressure sensitivity and fast response within a broad pressure range, high structure robustness, performance consistency, etc. This paper aims to engineer flexible capacitive pressure sensors with highly ordered porous dielectric microstructures and a 3D-printing-based fully solution-processable fabrication process. The proposed dielectric layer with uniformly distributed interior microporous can not only increase its compressibility and dynamic response within an extended pressure range but also enlarge its contact area with electrodes, contributing to a simultaneous improvement in the sensitivity, response speed, detection range, and structure robustness. Meanwhile, owing to its superior abilities in complex structure manufacturing and dimension controlling, the proposed 3D-printing-based fabrication process enables the consistent fabrication of the porous microstructure and thus guarantees device consistency. As a result, the prepared pressure sensors exhibit a high sensitivity of 0.21 kPa-1, fast response and relaxation times of 112 and 152 ms, an interface bonding strength of more than 455.2 kPa, and excellent performance consistency (≤5.47% deviation among different batches of sensors) and tunability. Encouraged by this, the pressure sensor is further integrated with a wireless readout circuit and realizes wireless wearable monitoring of various biosignals (pulse waves and heart rate) and body movements (from slight finger touch to large knee bending). Finally, the influence law of the feature parameters of the porous microstructure on device performance is established by the finite element method, paving the way for sensor optimization. This study motivates the development of flexible capacitive pressure sensors toward practical application.

Effect of Continuous Positive Airway Pressure on Incident Frailty in Elderly Patients with Obstructive Sleep Apnea: A Study Based on Propensity Score Matching.

Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Nanotoxicity of tungsten trioxide nanosheets containing oxygen vacancy to human umbilical vein endothelial cells.

Because of the excellent performance in photochemistry, WO3 is increasingly applied in the field of biology and medicine. However, little is known about the mechanism of WO3 cytotoxicity. In this work, WO3 nanosheets with oxygen vacancy are synthesized by solvothermal method, then characterized and added to culture medium of human umbilical vein endothelial cells (HUVECs) with different concentrations. We characterized and analyzed the morphology of nano-WO3 by transmission electron microscopy and calculated the specific data of oxygen vacancy by XPS. It is the first time the effect of WO3-x on cells that WO3-x can cause oxidative stress in HUVEC cells, resulting in DNA damage and thus promoting apoptosis. Transcriptome sequencing is performed on cells treated with low and high concentrations of WO3-x, and a series of key signals affecting cell proliferation and apoptosis are detected in differentially expressed genes, which indicates the research direction of nanotoxicity. The expression levels of key genes are also verified by quantitative PCR after cell treatment with different concentrations of WO3-x. This work fills the gap between the biocompatibility of nano WO3-x materials and molecular cytology and paves the way for investigating the mechanism and risks of oxygen vacancy in cancer therapy.

Highly Stretchable, Knittable, Wearable Fiberform Hydrovoltaic Generators Driven by Water Transpiration for Portable Self-Power Supply and Self-Powered Strain Sensor.

The development of excellently stretchable, highly mobile, and sustainable power supplies is of great importance for self-power wearable electronics. Transpiration-driven hydrovoltaic power generator (HPG) has been demonstrated to be a promising energy harvesting strategy with the advantages of negative heat and zero-carbon emissions. Herein, this work demonstrates a fiber-based stretchable HPG with the advantages of high output, portability, knittability, and sustainable power generation. Based on the functionalized micro-nano water diffusion channels constructed by the discarded mask straps (MSs) and oxidation-treated carbon nanomaterials, the applied water can continuously produce electricity during the spontaneous flow and diffusion. Experimentally, when a tiny 0.1 mL of water encounters one end of the proposed HPG, the centimeter-length device can yield a peak voltage of 0.43 V, peak current of 29.5 µA, and energy density of 5.833 mW h cm-3. By efficiently integrating multiple power generation units, sufficient output power can be provided to drive commercial electronic devices even in the stretched state. Furthermore, due to the reversibility of the electrical output during dynamic stretching-releasing, it can passively convert physiological activities and motion behaviors into quantifiable and processable current signals, opening up HPG's application in the field of self-powered wearable sensing.

The phonological congruency modulated long-term form priming of Chinese characters.

Elucidating the interaction between lexical processing and word learning is essential for a complete understanding of the underlying mechanisms of each of them. Long-term priming for words reflects an interplay between lexical processing and word learning. Although robust long-term priming effects have been found between two occurrences of the same word and between semantically similar words, it remains unclear whether long-term priming between orthographically similar words (i.e., long-term form priming) is a reliable effect. Following the theoretical analysis based on the connectionist framework, we articulated the possibility that long-term form priming might be modulated by the phonological congruency between the prime and target words, and that if this modulator was under control, reliable effects of long-term form priming would emerge. However, this hypothesis has not been adequately tested empirically. The present study tested this hypothesis by using Chinese phonograms and the phonetic radicals embedded in them as the prime and target items. In three experiments that varied in the types of stimuli and testing tasks, we consistently found that when the prime and target had the same phonology, naming the prime facilitated later processing of the target, while when they had different phonologies, the priming effect was inhibitory. These observations were consistent with the connectionist account of long-term priming for words. Our findings help confirm the reliability, generalizability, and robustness of long-term form priming and elucidate its underlying mechanisms, and suggesting promising future directions on the interactions between lexical processing and word learning.

SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke.

BACKGROUND AND OBJECTIVE: Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase-9 (MMP-9), Tissue inhibitor metalloproteinase-1 (TIMP-1), Monocyte Chemoattractant Protein-1 (MCP-1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features. METHOD: The concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS). RESULTS: The mean age was 69.0 ± 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (ß = 0.14; 95% confidence interval [CI], 0.04-0.24 ; p = 0.008 ). Restricted cubic spline regression demonstrated a dose-response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features. CONCLUSION: In summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction.

Clinical, Imaging Characteristics and Outcome of Intracerebral Hemorrhage Caused by Structural Vascular Lesions.

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

SAH and SAM/SAH ratio associate with acute kidney injury in critically ill patients: A case-control study.

BACKGROUND: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression and poor prognosis, which has high morbidity and mortality in hospitalized patients. DNA methylation plays an important role in the occurrence and progression of kidney disease, and aberrant methylation and certain altered methylation-related metabolites have been reported in AKI patients. However, the specific alterations of methylation-related metabolites in the AKI patients were not investigated clearly. METHOD: In this study, 61 AKI and 61 matched non-AKI inpatients were recruited after propensity score matching the age and hypertension. And 11 methylation-related metabolites in the plasma and urine of the two groups were quantified by using UHPLC-MS/MS method. RESULTS: Certain methylation-relate intermediates were up-regulated in the plasma (choline, trimethylamine N-oxide (TMAO), trimethyl lysine (TML), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)) and down-regulated in the urine of AKI inpatients (choline, betaine, TMAO, dimethylglycine (DMG), SAM and taurine). The correlation analysis revealed a relatively strong correlation between plasma SAH, SAM/SAH ratio and renal function index (serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), r = 0.523-0.616), and the correlation of urinary intermediates with renal function index was weaker than that in the plasma. Furthermore, receiver operating characteristic (ROC) analysis showed that plasma SAH and urinary SAM/SAH ratio represented the best distinguishing efficiency with AUC 0.844 and 0.794, respectively. Moreover, the findings of binary regression analysis demonstrated plasma choline, TMAO, TML, SAM and SAH were the risk markers of AKI (up-regulation in plasma, OR > 1), urinary choline, betaine, TMAO, DMG and SAM were protective markers of AKI (down-regulation in urine, OR < 1), and SAM/SAH ratio was a protective marker in plasma and urine (down-regulation in both two biofluids, OR = 0.510, 0.383-0.678 in plasma, OR = 0.904, 0.854-0.968 in urine), indicating the increased risk of AKI when combined with the alteration of plasma and urinary levels. CONCLUSION: The comprehensive analysis of plasma and urine samples from AKI inpatients offers a more extensive assessment of methylated metabolic alterations, suggesting a close relationship between AKI stress and altered methylation ability. The plasma level of SAH and SAM/SAH ratio and urinary SAM/SAH ratio both showed a strong correlation with renal function (SCr and eGFR) and good accuracy for distinguishing AKI in the two biomatrices, which exhibited promising prospects in predicting renal function decline and providing further information for the pathogenesis of AKI.

Association of Depression with Long-Term Cardiovascular Risks in Older Patients with Obstructive Sleep Apnea.

Introduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Depression is a crucial factor among the various factors that are associated with OSA and CVD. Purpose: This study was conducted with an aim to assess the prognostic significance of depression on the MACE in older patients with OSA. Patients and Methods: 1106 older patients with OSA, without myocardial infarction (MI), history of hospitalization for unstable angina, or heart failure at baseline were enrolled and followed up prospectively. Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were major adverse cardiovascular events (MACE). Each patient underwent polysomnography (PSG) and GDS-12 scale assessment. Those with an apnea-hypopnea index (AHI) greater than 5 were diagnosed with OSA, while those with a scale score greater than 3 were diagnosed with depression. Results: Among the 1106 older patients with OSA, depression was found in 133(12.0%) patients, 96(8.7%) patients experienced MACE during the follow-up. Depression was associated with a higher cumulative incidence of MACE in older patients with OSA. Multivariate analysis revealed that depression independently increased the risk of MACE (adjusted hazard ratio [aHR] = 2.29; 95% confidence interval [CI]: 1.34-3.90; P = 0.002). Subgroup analyses showed that male patients (aHR = 2.96; 95% CI: 1.52-5.77; P = 0.001), overweight-obese individuals (aHR = 2.98; 95% CI: 1.49-6.00; P = 0.002), and those with moderate-severe OSA (aHR = 2.82; 95% CI: 1.55-5.14; P = 0.001) and concurrent depression were at a higher risk for MACE. Conclusion: Depression is common in older patients with OSA in the absence of MI, hospitalization for unstable angina, or heart failure, and confers an independent, increased risk of MACE.

Efficacy and safety of transesophageal ultrasound-guided patent foramen ovale closure for migraine in adolescents.

Objective: This retrospective analysis aims to assess the efficacy of transesophageal ultrasound-guided patent foramen ovale (PFO) closure in treating migraine in adolescents and compare the therapeutic outcomes of PFO closure for migraine with and without aura. Methods: We conducted a retrospective analysis of 86 cases of adolescents (12-20 years old) who underwent PFO closure for migraine at our institution over the past 3 years. The efficacy was evaluated using the visual analogue scale (VAS), headache impact test (HIT)-6, and pediatric migraine disability assessment (PedMIDAS) scores, as well as by assessing the monthly frequency of migraine attacks, duration of each attack, and overall migraine burden. The patients were divided into two groups: an aura group (55 cases) and a non-aura group (31 cases) to investigate difference in therapeutic efficacy between the groups. The effect of residual shunt on migraine burden was assessed. Results: Among the 86 patients, 46 (54%) experienced complete remission of migraine, while 71 (83%) achieved a >50% reduction in migraine burden during the one-year follow-up period. Patients in the aura group showed more significant improvements in VAS, HIT-6, and PedMIDAS scores, as well as in monthly migraine attack frequency, duration of each attack, and overall migraine burden, than patients in the non-aura group. Moreover, patients with residual shunt did not exhibit statistically significant differences in therapeutic efficacy compared to patients with complete closure. Conclusion: PFO closure can effectively alleviate migraine symptoms in adolescents with migraine with concomitant PFO. The therapeutic efficacy is particularly pronounced for migraine with aura. Furthermore, minor levels of residual shunt have no effect on the improvement in migraine symptoms.

Advances in high-performance MEMS pressure sensors: design, fabrication, and packaging.

Pressure sensors play a vital role in aerospace, automotive, medical, and consumer electronics. Although microelectromechanical system (MEMS)-based pressure sensors have been widely used for decades, new trends in pressure sensors, including higher sensitivity, higher accuracy, better multifunctionality, smaller chip size, and smaller package size, have recently emerged. The demand for performance upgradation has led to breakthroughs in sensor materials, design, fabrication, and packaging methods, which have emerged frequently in recent decades. This paper reviews common new trends in MEMS pressure sensors, including minute differential pressure sensors (MDPSs), resonant pressure sensors (RPSs), integrated pressure sensors, miniaturized pressure chips, and leadless pressure sensors. To realize an extremely sensitive MDPS with broad application potential, including in medical ventilators and fire residual pressure monitors, the "beam-membrane-island" sensor design exhibits the best performance of 66 µV/V/kPa with a natural frequency of 11.3 kHz. In high-accuracy applications, silicon and quartz RPS are analyzed, and both materials show ±0.01%FS accuracy with respect to varying temperature coefficient of frequency (TCF) control methods. To improve MEMS sensor integration, different integrated "pressure + x" sensor designs and fabrication methods are compared. In this realm, the intercoupling effect still requires further investigation. Typical fabrication methods for microsized pressure sensor chips are also reviewed. To date, the chip thickness size can be controlled to be <0.1 mm, which is advantageous for implant sensors. Furthermore, a leadless pressure sensor was analyzed, offering an extremely small package size and harsh environmental compatibility. This review is structured as follows. The background of pressure sensors is first presented. Then, an in-depth introduction to MEMS pressure sensors based on different application scenarios is provided. Additionally, their respective characteristics and significant advancements are analyzed and summarized. Finally, development trends of MEMS pressure sensors in different fields are analyzed.

In Situ Study of the Magnetic Field Gradient Produced by a Miniature Bi-Planar Coil for Chip-Scale Atomic Devices.

The miniaturization of quantum sensors is a popular trend for the development of quantum technology. One of the key components of these sensors is a coil which is used for spin modulation and manipulation. The bi-planar coils have the advantage of producing three-dimensional magnetic fields with only two planes of current confinement, whereas the traditional Helmholtz coils require three-dimensional current distribution. Thus, the bi-planar coils are compatible with the current micro-fabrication process and are quite suitable for the compact design of the chip-scale atomic devices that require stable or modulated magnetic fields. This paper presents a design of a miniature bi-planar coil. Both the magnetic fields produced by the coils and their inhomogeneities were designed theoretically. The magnetic field gradient is a crucial parameter for the coils, especially for generating magnetic fields in very small areas. We used a NMR (Nuclear Magnetic Resonance) method based on the relaxation of 131Xe nuclear spins to measure the magnetic field gradient in situ. This is the first time that the field inhomogeneities of the field of such small bi-planar coils have been measured. Our results indicate that the designed gradient caused error is 0.08 for the By and the Bx coils, and the measured gradient caused error using the nuclear spin relaxation method is 0.09±0.02, suggesting that our method is suitable for measuring gradients. Due to the poor sensitivity of our magnetometer under a large Bz bias field, we could not measure the Bz magnetic field gradient. Our method also helps to improve the gradients of the miniature bi-planar coil design, which is critical for chip-scale atomic devices.

Factors influencing new-onset hypertension in elderly patients with obstructive sleep apnea: A multicenter cohort study.

Investigating the influencing factors of new-onset hypertension in the elderly with obstructive sleep apnea (OSA). 450 Chinese older patients with OSA who were non-hypertensive at baseline were enrolled. All patients had undergone polysomnography monitoring in the multicenter study. The primary endpoint was incident hypertension. Kaplan-Meier survival analysis was performed, and multivariate Cox proportional hazards models were generated to determine the factors influencing new-onset hypertension. A total of 176 (39.1%) patients developed hypertension. The hypertension group had older age, higher hemoglobin (Hb) level and apnea-hypopnea index (AHI) values than the non-hypertension group (all p < 0.05). During the median 33-month follow-up period, multivariate Cox analysis showed age (hazard ratio (HR) = 1.039, 95% confidence interval (95% CI): 1.016-1.062), AHI (HR = 1.015, 95% CI: 1.007-1.023) and Hb level (HR = 1.016, 95% CI: 1.008-1.025) were independent predictors of new-onset hypertension. However, continuous positive airway pressure (CPAP; HR = 0.508, 95% CI: 0.271-0.951) reduced the risk of developing hypertension. Notably, the subgroup analysis demonstrated that the plasma glucose level (HR = 1.168, 95% CI: 1.029-1.326) was a risk factor for male patients. Besides length of time with the pulse oxygen saturation less than 90% (Tsat90; HR = 1.005, 95% CI: 1.003-1.007), body mass index (BMI; HR = 1.170, 95% CI: 1.043-1.311), and dyslipidemia (HR = 2.335, 95% CI: 1.144-4.766) had statistically significant effects on the incidence of hypertension in certain subgroups. Although this study lacked analysis of items such as living habits and medication, it did show age, AHI, Hb and CPAP affected the development of hypertension in elderly OSA patients. These findings suggested that targeted interventions in specific populations may be more effective in preventing hypertension.