Universal relation between the conditional auto-correlation function and the cross-correlation function of biphotons.

We systematically studied the relation between the conditional auto-correlation function (CACF) and cross-correlation function (CCF) of biphotons or pairs of single photons. The biphotons were generated from a heated atomic vapor via the spontaneous four-wave mixing (SFWM) process. In practical usage, one single photon of a pair is utilized as the heralding photon, and another is employed as the heralded photon. Motivated by the data of CACF of the heralded photons versus CCF, we proposed a universal formula to predict the CACF. The derived formula was based on general theory and is also valid for the biphoton generation process of spontaneous parametric down-conversion (SPDC). With the formula, we utilized the experimentally determined parameters to predict CACFs, which can well agree with the measured CACFs. The proposed formula enables one to quantitatively know the CACF of heralded single photons without the measurement of Hanbury-Brown-Twiss-type three-fold coincidence count. This study provides a better understanding of biphoton generation using the SFWM or SPDC process. Our work demonstrates a valuable tool for analyzing a vital property of how the heralded photons are close to Fock-state single photons.

Effect of Cu Film Thickness on Cu Bonding Quality and Bonding Mechanism.

In the hybrid bonding process, the final stage of chemical mechanical polishing plays a critical role. It is essential to ensure that the copper surface is recessed slightly from the oxide surface. However, this recess can lead to the occurrence of interfacial voids between the bonded copper interfaces. To examine the effects of copper film thickness on bonding quality and bonding mechanisms in this study, artificial voids were intentionally introduced at the bonded interfaces at temperatures of 250 °C and 300 °C. The results revealed that as the thickness of the copper film increases, there is an increase in the bonding fraction and a decrease in the void fraction. The variations in void height with different copper film thicknesses were influenced by the bonding mechanism and bonding fraction.

Serotypes, virulence factors and multilocus sequence typing of Glaesserella parasuis from diseased pigs in Taiwan.

Background: Glaesserella parasuis (G. parasuis) belongs to the normal microbiota of the upper respiratory tract in the swine, but virulent strains can cause systemic infections commonly known as Glässer's disease that leads to significant economic loss in the swine industry. Fifteen serotypes of G. parasuis have been classified by gel immunodiffusion test while the molecular serotyping based on variation within the capsule loci have further improved the serotype determination of unidentified field strains. Serovar has been commonly used as an indicator of virulence; however, virulence can be significantly differ in the field isolates with the same serotype. To date, investigations of G. parasuis isolated in Taiwan regarding antimicrobial resistance, serotypes, genotypes and virulence factors remain unclear. Methods: A total of 276 G.parasuis field isolates were collected from 263 diseased pigs at the Animal Disease Diagnostic Center of National Chiayi University in Taiwan from January 2013 to July 2021. Putative virulence factors and serotypes of the isolates were identified by polymerase chain reaction (PCR) and antimicrobial susceptibility testing was performed by microbroth dilution assay. Additionally, the epidemiology of G. parasuis was characterized by multilocus sequence typing (MLST). Results: Serotype 4 (33.3%) and 5 (21.4%) were the most prevalent, followed by nontypable isolates (15.9%), serotype 13 (9.4%), 12 (6.5%), 14 (6.2%), 7 (3.3%), 1 (1.8%), 9 (1.1%), 11 (0.7%) and 6 (0.4%). Nine out of 10 putative virulence factors showed high positive rates, including group 1 vtaA (100%), fhuA (80.4%), hhdA (98.6%), hhdB (96.0%), sclB7 (99.6%), sclB11 (94.9%), nhaC (98.2%), HAPS_0254 (85.9%), and cirA (99.3%). According to the results of antimicrobial susceptibility testing, ceftiofur and florfenicol were highly susceptible (>90%). Notably, 68.8% isolates showed multidrug resistance. MLST revealed 16 new alleles and 67 new sequence types (STs). STs of these isolated G. parasuis strains were classified into three clonal complexes and 45 singletons by Based Upon Related Sequence Types (BURST) analysis. All the G. parasuis strains in PubMLST database, including strains from the diseased pigs in the study, were defined into two main clusters by Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Most isolates in this study and virulent isolates from the database were mainly located in cluster 2, while cluster 1 included a high percentage of nasal isolates from asymptomatic carriers. In conclusion, this study provides current prevalence and antimicrobial susceptibility of G. parasuis in Taiwan, which can be used in clinical diagnosis and treatment of Glässer's disease.

Experimental Demonstration of Stationary Dark-State Polaritons Dressed by Dipole-Dipole Interaction.

Dark-state polaritons (DSPs) based on the effect of electromagnetically induced transparency are bosonic quasiparticles, representing the superpositions of photons and atomic ground-state coherences. It has been proposed that stationary DSPs are governed by the equation of motion closely similar to the Schrödinger equation and can be employed to achieve Bose-Einstein condensation (BEC) with transition temperature orders of magnitude higher than that of the atomic BEC. The stationary-DSP BEC is a three-dimensional system and has a far longer lifetime than the exciton-polariton BEC. In this Letter, we experimentally demonstrated the stationary DSP dressed by the Rydberg-state dipole-dipole interaction (DDI). The DDI-induced phase shift of the stationary DSP was systematically studied. Notably, the experimental data are consistent with the theoretical predictions. The phase shift can be viewed as a consequence of elastic collisions. In terms of thermalization to achieve BEC, the µm^{2}-size interaction cross section of the DDI can produce a sufficient elastic collision rate for the stationary DSPs. This Letter makes a substantial advancement toward the realization of the stationary-DSP BEC.

Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention: A Meta-analysis and Meta-Regression.

Importance: The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated. Objective: To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA). Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022. Study Selection: Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events. Main Outcomes and Measures: The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events. Results: Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, -0.06; 95% CI, -0.08 to -0.03; DBP: regression slope, -0.17; 95% CI, -0.26 to -0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events. Conclusions and Relevance: More intensive blood pressure-lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.

Targeting the Phosphatidylserine-Immune Checkpoint with a Small-Molecule Maytansinoid Conjugate.

Ligand-targeting drug delivery systems have made significant strides for disease treatments with numerous clinical approvals in this era of precision medicine. Herein, we report a class of small molecule-based immune checkpoint-targeting maytansinoid conjugates. From the ligand targeting ability, pharmacokinetics profiling, in vivo anti-pancreatic cancer, triple-negative breast cancer, and sorafenib-resistant liver cancer efficacies with quantitative mRNA analysis of treated-tumor tissues, we demonstrated that conjugate 40a not only induced lasting regression of tumor growth, but it also rejuvenated the once immunosuppressive tumor microenvironment to an "inflamed hot tumor" with significant elevation of gene expressions that were not accessible in the vehicle-treated tumor. In turn, the immune checkpoint-targeting small molecule drug conjugate from this work represents a new pharmacodelivery strategy that can be expanded with combination therapy with existing immune-oncology treatment options.

Feasibility and Potential Effects of Robot-Assisted Passive Range of Motion Training in Combination with Conventional Rehabilitation on Hand Function in Patients with Chronic Stroke.

OBJECTIVE: To assess the effects of exoskeleton robot-assisted passive range of motion for induction training in combination with conventional hand rehabilitation in patients with chronic stroke. DESIGN: Single-cohort feasibility study. SUBJECTS: Chronic stroke with severe upper extremity hemiparesis. METHODS: Thirty sessions of therapy over a period of 10 weeks. Each session started with 30 min robot-assisted passive range of motion for the hand, followed by 30 min conventional hand rehabilitation. The Fugl-Meyer Assessment for upper extremity, arm subscore of Motricity Index, Functional Independence Measure and Fugl-Meyer assessment for sensation (Fugl-Meyer assessment-sensory) were conducted at pre-intervention (pre) and after the 16th (16-post) and 30th (30-post) sessions of interventions. RESULTS: Twelve patients with chronic stroke were recruited. The Fugl-Meyer assessment for upper extremity (16-post vs 30-post, p = 0.011), arm subscore of Motricity Index (pre vs 30-post, p = 0.012) and Functional Independence Measure (pre vs 30-post, p = 0.007; 16- post vs 30-post, p = 0.016) improved significantly after the therapy. However, FMA-sensory did not change significantly. CONCLUSION: Exoskeleton robot-assisted passive range of motion of the hand using an exoskeleton can be considered as an induction therapy before starting conventional therapy for hand rehabilitation in patients with chronic stroke. Further randomized control trials are needed to verify the therapeutic benefits.

Synthesis and Evaluation of Small Molecule Drug Conjugates Harnessing Thioester-Linked Maytansinoids.

Ligand-targeting drug conjugates are a class of clinically validated biopharmaceutical drugs constructed by conjugating cytotoxic drugs with specific disease antigen targeting ligands through appropriate linkers. The integrated linker-drug motif embedded within such a system can prevent the premature release during systemic circulation, thereby allowing the targeting ligand to engage with the disease antigen and selective accumulation. We have designed and synthesized new thioester-linked maytansinoid conjugates. By performing in vitro cytotoxicity, targeting ligand binding assay, and in vivo pharmacokinetic studies, we investigated the utility of this new linker-drug moiety in the small molecule drug conjugate (SMDC) system. In particular, we conjugated the thioester-linked maytansinoids to the phosphatidylserine-targeting small molecule zinc dipicolylamine and showed that Zn8_DM1 induced tumor regression in the HCC1806 triple-negative breast cancer xenograft model. Moreover, in a spontaneous sorafenib-resistant liver cancer model, Zn8_DM1 exhibited potent antitumor growth efficacy. From quantitative mRNA analysis of Zn8_DM1 treated-tumor tissues, we observed the elevation of gene expressions associated with a "hot inflamed tumor" state. With the identification and validation of a plethora of cancer-associated antigens in the "omics" era, this work provided the insight that antibody- or small molecule-based targeting ligands can be conjugated similarly to generate new ligand-targeting drug conjugates.

Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: The aim of the meta-analysis of randomized controlled trials (RCTs) was to compare the effectiveness of glycemic control and hypoglycemia risk of combination therapy (metformin plus a low hypoglycemic risk antidiabetic drug) vs. standard metformin monotherapy, in patients with untreated type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through October 31, 2021 to find relevant RCTs. Efficacy outcomes were changes in hemoglobulin A1c (HbA1c) and fast plasma glucose (FPG) from baseline as well as proportion of patients achieving HbA1c < 7%; the safety outcome was hypoglycemia risk. RESULTS: We identified 14 RCTs comprising 5326 patients with untreated T2DM. Mean treatment duration was 28.1 weeks. Pooled results showed that compared to metformin monotherapy, combination therapy was associated with a reduction in HbA1c (mean difference: -0.48 %, -0.58 to - 0.38) and FPG (mean difference: -0.92 mmol/L, -1.14 to - 0.69), and more patients achieving HbA1c < 7% (odds ratio: 2.21, 1.87 to 2.60). Hypoglycemic events and people experiencing hypoglycemia were not different between 2 groups. CONCLUSIONS: Initial combination of metformin plus a low hypoglycemic risk antidiabetic drug may achieve better glycemic control, without a rise in hypoglycemia, in patients with untreated T2DM.

Respiratory Arousals in Patients with Very Severe Obstructive Sleep Apnea and How They Change after a Non-Framework Surgery.

Respiratory arousal is the change from a state of sleep to a state of wakefulness following an apnea or hypopnea. In patients with obstructive sleep apnea (OSA), it could have a helpful role to activate upper airway muscles and the resumption of airflow and an opposing role to contribute to greater ventilatory instability, continue cycling, and likely exacerbate OSA. Patients with very severe OSA (apnea-hypopnea index (AHI) ≥ 60 events/h) may have specific chemical (e.g., possible awake hypercapnic hypoxemia) and mechanical (e.g., restricted dilator muscles) stimuli to initiate a respiratory arousal. Little was reported about how respiratory arousal presents in this distinct subgroup, how it relates to AHI, Epworth Sleepiness Scale (ESS), body mass index (BMI), and oxygen saturation, and how a non-framework surgery may change it. Here, in 27 patients with very severe OSA, we show respiratory arousal index was correlated with each of AHI, mean oxyhemoglobin saturation of pulse oximetry (SpO2), mean desaturation, and desaturation index, but not in BMI or ESS. The mean (53.5 events/h) was higher than other reports with less severe OSAs in the literature. The respiratory arousal index can be reduced by about half (45.3%) after a non-framework multilevel surgery in these patients.

Ultrasound in postresuscitation care: a narrative review.

The efficacy of ultrasound (US) in real-time differential diagnosis and guiding further treatment decisions has been well demonstrated in prearrest conditions and during resuscitation. Evidence is limited regarding the application of US in postresuscitation care. Most of the patients following resuscitation remain comatose, and the requirement for transportation to other examination rooms increases their risk of injury. US can be performed at the bedside with high accessibility and timeliness without radiation. This narrative review provides an overview of current evidence regarding the application of US in identifying the cause of cardiac arrest (CA), hemodynamic monitoring, and prognostication in postresuscitation care. For identifying the cause of CA, cardiac US is mainly used to detect regional wall motion abnormality. However, postarrest myocardial dysfunction would confound the sonographic findings that a combination of electrocardiograms and biomarkers besides the cardiac US could improve the positive predictive value of coronary artery disease. For hemodynamic monitoring, left ventricular outlet tract velocity time integral has the best performance in predicting fluid responsiveness in conjunction with the passive leg raising test. The RUSH protocol assists in determining the subtypes of shock with high sensitivity and specificity in hypovolemic, cardiogenic, or obstructive shock. Evidence regarding the application of US for prognostication is still limited, and further evaluation should be needed.

Negative impact of the hypopnea index or duration increase after a non-frame work surgery in patients with very severe obstructive sleep apnea.

A non-framework surgery could change the postoperative components of breathing disturbances and increase the frequency or duration of hypopnea in patients with very severe obstructive sleep apnea (OSA). Either an increase of hypopnea index, which increases apnea-hypopnea index (AHI), or an increase of its duration raises the concern of worsening the oxygen desaturation and so morbidity and mortality associated with OSA. It is unclear how the oxygen saturation would change in those having increased frequency or duration of hypopneas after the surgery. Here in 17 patients with AHI ≥ 60 events/h, having increased frequency or duration of hypopneas after the non-framework surgery, the results show that the surgery improved oxygen saturation by reducing obstructive-apnea index (36.1 events/h) and duration (8.6 s/event), despite it increased hypopnea index (16.8 events/h) and duration (9.8 s/event). The surgery improved the average of the mean oxyhemoglobin saturation of pulse oximetry (SpO2) by 2.8% (toward a ceiling mean of 94.3%), mean minimal SpO2 by 7.5%, and mean desaturation by 5%. The results suggest sufficient apnea reduction and shift from apnea to hypopnea may mask the negative impact of the increase of hypopnea index or duration and improve postoperative mean SpO2, minimal SpO2, and mean desaturation.

Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention: A Meta-analysis of Randomized Clinical Trials.

IMPORTANCE: The benefits and risks associated with intensive low-density lipoprotein cholesterol (LDL-C)-lowering statin-based therapies to lessen the risk of recurrent stroke have not been established. OBJECTIVE: To conduct a meta-analysis of randomized clinical trials to evaluate the association of more intensive vs less intensive LDL-C-lowering statin-based therapies with outcomes for patients with ischemic stroke. DATA SOURCES: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1970, to July 31, 2021. STUDY SELECTION: This meta-analysis included randomized clinical trials that compared more intensive vs less intensive LDL-C-lowering statin-based therapies and recorded the outcome of recurrent stroke among patients with stroke. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Relative risk (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive LDL-C lowering with primary and secondary outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent stroke, and the secondary outcomes were major cardiovascular events and hemorrhagic stroke. RESULTS: The final analysis included 11 randomized clinical trials with 20 163 patients (13 518 men [67.0%]; mean [SD] age, 64.9 [3.7] years) with stroke. The mean follow-up was 4 years (range, 1-6.1 years). Pooled results showed that more intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke compared with less intensive LDL-C-lowering statin-based therapies (absolute risk, 8.1% vs 9.3%; RR, 0.88; 95% CI, 0.80-0.96) and that the benefit associated with these LDL-C-lowering therapies was not different among LDL-C-lowering strategies (statins vs no statins: RR, 0.90; 95% CI, 0.81-1.01; more statins or ezetimibe vs less statins or ezetimibe: RR, 0.77; 95% CI, 0.62-0.96; and proprotein convertase subtilisin/kexin type 9 inhibitors plus statins vs placebo plus statins: RR, 0.90; 95% CI, 0.71-1.15; P = .42 for interaction). More intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of major cardiovascular events, but with an increased risk of hemorrhagic stroke, compared with less intensive LDL-C-lowering statin-based therapies. More intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke in trials with all patients having evidence of atherosclerosis (RR, 0.79; 95% CI, 0.69-0.91), but not in trials with most patients not having evidence of atherosclerosis (RR, 0.95; 95% CI, 0.85-1.07; P = .04 for interaction), compared with less intensive LDL-C-lowering statin-based therapies. CONCLUSIONS AND RELEVANCE: This study suggests that the benefits and risks of more intensive LDL-C-lowering statin-based therapies for recurrent stroke risk reduction might be more favorable than the benefits and risks of less intensive LDL-C-lowering statin-based therapies, especially for patients with evidence of atherosclerosis.

The Beneficial Effects of Combining Anti-Aß Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer's Disease in APP/PS1 Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aß antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aß and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aß levels, and insoluble forms of Aß were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aß phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aß pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

[Factors Influencing Patient Decisions Regarding Cancer Clinical Trial Participation: A Systematic Review].

BACKGROUND: Cancer is the top cause of death in Taiwan. Cancer clinical trials are crucial for developing new treatments. Understanding the motivations and barriers related to the factors of influence on patient decisions regarding participation in cancer clinical trials may help clinical researchers improve patients' understanding of clinical trials and improve their ability to make autonomous decisions regarding informed consent. PURPOSE: This study was designed to explore the factors affecting patient decisions regarding cancer clinical trial participation using a systematic review of the literature. METHODS: A systematic review was used. Articles were retrieved from electronic databases including Cochrane Library, Embase, PubMed, CINAHLE, and Scopus. The following keywords and MeSH terms were used to search for articles on cancer, clinical trials, participation, factors or motivations, and decision making. A total of 9353 articles published from 2011 to January 2021 that matched the search criteria were extracted. After screening the topics, deleting repetitions, and doing critical appraisals, 40 articles were selected for analysis. Research quality was assessed using Joanna Briggs Institute Levels of Evidence criteria. RESULTS: Eight motivations and nine barriers were found to significantly influence patient participation in cancer clinical trials. These motivations were: (1) trust in health professionals, (2) hope for therapeutic benefits, (3) the last treatment option, (4) altruism, (5) family support, (6) extra care, (7) patients' or others' past therapy experience, and (8) other demographic factors. The barriers to participation identified were: (1) fear of side effects or treatment efficacy, (2) concerns about trial requirements and randomization, (3) heavy financial burden, (4) inability to maintain quality of life, (5) inability to participate due to disease progression, (6) having treatment preferences, (7) health professionals' negative attitudes toward clinical trials, (8) family opposition, and (9) providing trial information at an inappropriate time. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Eight motivational factors and nine barriers influencing patient decisions regarding cancer clinical trial participation were extracted from the selected articles. In addition to personal and situational factors, family and health professionals were found to influence patient decisions regarding cancer clinical trial participation. The authors hope that the findings of this study help clinical researchers further improve patient understanding of clinical trials and help patients make autonomous decisions with regard to informed consent.

Associations between urinary cysteine-rich protein 61 excretion and kidney function decline in outpatients with chronic kidney disease: a prospective cohort study in Taiwan.

OBJECTIVES: To examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline. DESIGN: An observational cohort study. SETTING: In the nephrology outpatient clinics of a tertiary hospital in Taiwan. PARTICIPANTS: We enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women. PRIMARY OUTCOME MEASURES: Urinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m2/year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables. RESULTS: The urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up. CONCLUSIONS: Elevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning.

Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan.

OBJECTIVE: We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). PATIENTS AND METHODS: We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. RESULTS: Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06-2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. CONCLUSIONS: Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

The risk of cardiac mortality in patients with status epilepticus: A 10-year study using data from the Centers for Disease Control and Prevention (CDC).

OBJECTIVE: To explore whether status epilepticus affected cardiac mortality. METHODS: We used the 2008-2017 multicause mortality data of the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiological Research. The status epilepticus group included patients whose death certificates mentioned status epilepticus as contributing to death. The non-status epilepticus group included patients whose death certificates mentioned epilepsy, other and unspecified convulsions, febrile convulsions, or post-traumatic seizures, as contributing to death. The outcomes for evaluation were death certificates that indicated that myocardial infarction, arrhythmia, heart failure, or cardiac arrest (CA) was the immediate cause of death. The numbers of deaths and population sizes by categorical demographics were recorded and subjected to multiple logistic regression analysis. RESULTS: Among the 14,487 death certificates in status epilepticus group; 3080 patients (21.3%) died of CA. When clinical records were compared to autopsy data, females were at a lower risk of myocardial infarction (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.51-0.61). Patients aged 45-65 years and older than 65 years were at a higher risk of developing all four cardiac complications. Status epilepticus was associated with higher risks of arrhythmia (OR: 1.55, 95% CI: 1.11-2.15) and CA (OR: 4.34, 95% CI: 3.49-5.39) but a reduced risk of myocardial infarction (OR: 0.42, 95% CI: 0.30-0.57) as the cause of immediate death. CONCLUSION: The frequency of CA in patients with status epilepticus increased between 2008 and 2017. Male and elderly patients were at a higher risk of cardiogenic mortality.

Generation of sub-MHz and spectrally-bright biphotons from hot atomic vapors with a phase mismatch-free scheme.

We utilized the all-copropagating scheme, which maintains the phase-match condition, in the spontaneous four-wave mixing (SFWM) process to generate biphotons from a hot atomic vapor. The linewidth and spectral brightness of our biphotons surpass those of the biphotons produced with the hot-atom SFWM in the previous works. Moreover, the generation rate of the sub-MHz biphoton source in this work can also compete with those of the sub-MHz biphoton sources of the cold-atom SFWM or cavity-assisted spontaneous parametric down conversion. Here, the biphoton linewidth is tunable for an order of magnitude. As we tuned the linewidth to 610 kHz, the generation rate per linewidth is 1,500 pairs/(s·MHz) and the maximum two-photon correlation function, gs,as(2), of the biphotons is 42. This gs,as(2) violates the Cauchy-Schwarz inequality for classical light by 440 folds, and demonstrates that the biphotons have a high purity. By increasing the pump power by 16 folds, we further enhanced the generation rate per linewidth to 2.3×104 pairs/(s·MHz), while the maximum gs,as(2) became 6.7. In addition, we are able to tune the linewidth down to 290±20 kHz. This is the narrowest linewidth to date among all single-mode biphoton sources of room-temperature and hot media.