Intense electric field optical sensor based on Fabry-Perot interferometer utilizing LiNbO3 crystal.

A novel intense electric field optical sensor based on Fabry-Perot interferometer utilizing LiNbO3 crystal is proposed and demonstrated. Compared to the traditional bulk-type electric field optical sensors, this sensor unit requires only a LiNbO3 and two collimators, eliminating the need for quarter wave-plate and allowing for measurement of electric field without limitation by half wave voltage. The Vernier effect, generated by birefringence of LiNbO3, is utilized to enhance the sensitivity of electric field measurement, which does not require additional reference cavity. Both theoretical and experimental results illustrate that the wavelength shift of the sensor is linear function of the measured electric field. In the range of 0∼1010 kV/m, the sensor's measurement sensitivity is 2.22 nm/E (V/µm) with detection limit of 1.27 × 10-2 E. Additionally, an MZI is proposed for temperature compensation, resulting in a standard deviation of spectrum variation after compensation of only 5.01 × 10-3. Applications using this sensor confirmed that it is expected to find widespread use in measurements of intense transient electric fields.

Enhanced toluene gas-sensing properties of MEMS sensor based on Pt-loaded SnO2nanoparticles.

Rapid detection of low concentration toluene is highly desirable in environment monitoring, industrial processes, medical diagnosis, etc. In this study, we prepared Pt-loaded SnO2monodispersed nanoparticles through hydrothermal method and assembled a sensor based on micro-electro-mechanical system (MEMS) to detect toluene. Compared with the pure SnO2, the 2.92 wt% Pt-loaded SnO2sensor exhibits a 2.75 times higher gas sensitivity to toluene at about 330 °C. Meanwhile, the 2.92 wt% Pt-loaded SnO2sensor also has a stable and good response to 100 ppb of toluene. Its theoretical detection limit is calculated as low as 12.6 ppb. Also, the sensor has a short response time of ∼10 s to different gas concentrations, as well as the excellent dynamic response-recovery characteristics, selectivity, and stability. The improved performance of Pt-loaded SnO2sensor can be explained by the increase of oxygen vacancies and chemisorbed oxygen species. The electronic and chemical sensitization of Pt to SnO2-based sensor, together with small size and fast gas diffusion of the MEMS design ensured fast response and ultra-low toluene detection. This provides new ideas and decent prospect for developing miniaturized, low-power-consumption, and portable application of gas sensing devices.

Increased EEG gamma power under exposure to drug-related cues: a translational index for cue-elicited craving in METH-dependent individuals.

BACKGROUND: This study explored the feasibility of using EEG gamma-band (30-49 Hz) power as an index of cue-elicited craving in METH-dependent individuals. METHODS: Twenty-nine participants dependent on methamphetamine (METH) and 30 healthy participants were instructed to experience a METH-related virtual reality (VR) social environment. RESULTS: Individuals with METH dependence showed significantly stronger self-reported craving and higher gamma power in a VR environment than healthy individuals. In the METH group, the VR environment elicited a significant increase in gamma power compared with the resting state. The METH group then received a VR counterconditioning procedure (VRCP), which was deemed useful in suppressing cue-induced reactivity. After VRCP, participants showed significantly lower self-reported craving scores and gamma power when exposed to drug-related cues than the first time. CONCLUSIONS: These findings suggest that the EEG gamma-band power may be a marker of cue-induced reactivity in patients with METH dependence.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method: Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (p < 0.001), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p=0.18). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion: Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Neural Stochastic Differential Equations with Neural Processes Family Members for Uncertainty Estimation in Deep Learning.

Existing neural stochastic differential equation models, such as SDE-Net, can quantify the uncertainties of deep neural networks (DNNs) from a dynamical system perspective. SDE-Net is either dominated by its drift net with in-distribution (ID) data to achieve good predictive accuracy, or dominated by its diffusion net with out-of-distribution (OOD) data to generate high diffusion for characterizing model uncertainty. However, it does not consider the general situation in a wider field, such as ID data with noise or high missing rates in practice. In order to effectively deal with noisy ID data for credible uncertainty estimation, we propose a vNPs-SDE model, which firstly applies variants of neural processes (NPs) to deal with the noisy ID data, following which the completed ID data can be processed more effectively by SDE-Net. Experimental results show that the proposed vNPs-SDE model can be implemented with convolutional conditional neural processes (ConvCNPs), which have the property of translation equivariance, and can effectively handle the ID data with missing rates for one-dimensional (1D) regression and two-dimensional (2D) image classification tasks. Alternatively, vNPs-SDE can be implemented with conditional neural processes (CNPs) or attentive neural processes (ANPs), which have the property of permutation invariance, and exceeds vanilla SDE-Net in multidimensional regression tasks.

PAPD5/7 Are Host Factors That Are Required for Hepatitis B Virus RNA Stabilization.

RG7834 is a potent, orally bioavailable small-molecule inhibitor of hepatitis B virus (HBV) gene expression that belongs to the dihydroquinolizinone (DHQ) chemical class and uniquely blocks production of both viral DNA and antigens. In this study, we used DHQ compounds as tools in a compound-based adaptation version of the yeast three-hybrid screen to identify the cognate cellular protein targets, the non-canonical poly(A) RNA polymerase associated domain containing proteins 5 and 7 (PAPD5 and PAPD7). Interaction with RG7834 was mapped to the catalytic domains of the two cellular enzymes. The role of PAPD5 and PAPD7 in HBV replication was confirmed by oligonucleotide-mediated knockdown studies that phenocopied the result seen with RG7834-treated HBV-infected hepatocytes. The greatest effect on HBV gene expression was seen when PAPD5 and PAPD7 mRNAs were simultaneously knocked down, suggesting that the two cellular proteins play a redundant role in maintaining HBV mRNA levels. In addition, as seen previously with RG7834 treatment, PAPD5 and PAPD7 knockdown led to destabilization and degradation of HBV mRNA without impacting production of viral RNA transcripts. Conclusion: We identify PAPD5 and PAPD7 as cellular host factors required for HBV RNA stabilization and as therapeutic targets for the HBV cure.

Monitoring Strain Response of Epoxy Resin during Curing and Cooling Using an Embedded Strain Gauge.

The present work describes the monitoring system of the real-time strain response on the curing process of epoxy resin from the initial point of curing to the end, and the change in strain during temperature changes. A simple mould was designed to embed the strain gauge, thermometer, and quartz standard sample into the epoxy resin, so that the strain and the temperature were simultaneously measured and recorded. A cryogenic-grade epoxy resin was tested and the Differential Scanning Calorimetry (DSC) was used to analyse the curing process. Based on the DSC results, three curing processes were adopted to investigate their influence on strain response as well as residual strain of the epoxy resin. Moreover, impact strength of the epoxy resin with various curing temperatures were tested and the results indicate that the curing plays a crucial role on the mechanical properties. The method will find cryogenic application of epoxy adhesives and epoxy resin based composites to monitor the strain during the curing process as well as the cryogenic service.

Selective impairments of alerting and executive control in HIV-infected patients: evidence from attention network test.

BACKGROUND: Attention ability can be subdivided into three functionally independent networks, i.e., alerting network, orienting network, and executive network. Previous literature has documented that deficits in attention are a common consequence of HIV infection. However, the precise nature of deficits of attention in HIV-infected patients is poorly understood. Accordingly, the aim of the study was to identify whether the HIV-infected patients showed a specific attention network deficit or a general attentional impairment. METHODS: We investigated 27 HIV-infected patients and 31 normal controls with the Attention Network Test (ANT). RESULTS: The patients exhibited less efficient alerting network and executive network than controls. No significant difference was found in orienting network effect between groups. Our results also indicate a tendency for poorer efficiency on alerting attention and executive attention in patients with CD4 ≤ 200. CONCLUSIONS: Our findings suggest that HIV-infected patients exhibited selective impairments of attention network of alerting and executive control. The link between lower CD4 T cell count and poorer attention network function imply the importance of starting antiretroviral therapy earlier to avoid irreversible neurocognitive impairment.

Stress and hope distinguish individuals with suicidal plan from suicide ideators among Chinese college students.

Background: Suicide among college students is a significant public health concern in China. While suicidal ideation serves as a crucial predictor of subsequent suicidal plans and behaviors, it is important to recognize that most instances of suicidal ideation may only be fleeting thoughts that do not progress to an actual plan. Therefore, it is imperative to identify the factors associated with the transition from suicidal ideation to a concrete plan. Consequently, this study aims to investigate whether certain frequently cited factors can differentiate individuals who have formulated a specific suicidal plan from those who have experienced suicidal thoughts without planning, based on data obtained through a cross-sectional survey. Materials and methods: This survey was conducted as part of routine mental health assessments among second-year college students in October 2023. Data from a total of 4,858 second-year college students were utilized for the final analyses. Two survey questions were employed to identify past-year suicidal ideation and past-year suicidal plan. All participants were required to complete various assessments, including the Chinese version of Depression Anxiety Stress Scale 21 items (DASS-21), the Chinese version of Gratitude Questionnaire-six items (GQ-6), the Chinese version of Meaning in Life Questionnaire (MLQ), and the Chinese version of State Hope Scale (SHS). Results: Among 4,858 participants, a total of 134 individuals (2.8%) were confirmed to have experienced past-year suicidal ideation. Out of these, 53 (1.1% overall) reported having a past-year suicidal plan, accounting for approximately 39.6% of those with suicidal ideation. Logistic regression analyses revealed that while most potential variables differentiated between students with and without suicidal ideation, only two factors stood out in distinguishing individuals with a suicidal plan from those who had not made such plans despite experiencing suicidal thoughts-presence of stress (OR=2.49, 95% CI: 1.04-5.96) and lower scores of hope agency (OR=0.84, 95% CI: 0.72-0.98). Conclusion: These findings suggest that the stress may contribute to susceptibility for transitioning from mere thoughts to actual planning regarding suicide; conversely, hope agency appears to offer protection against this transition process. Therefore, we advocate for targeted interventions aimed at fostering hope among individuals who have encountered adverse and stressful life events.

Diminished representational momentum for physical states in patients with depressive disorder.

The representational momentum for physical state changes refers to the fact that we remember objects as more changed in physical state than they actually were. It has been well documented that depressive disorder is associated with impairment of time perception. Thus, the present work was conducted with the aim to investigate the representational momentum for physical state changes in patients with depressive disorder, firstly. Forty patients with depressive disorder and forty-two healthy controls were administrated with the task of representational momentum for physical state changes and task of time perception. The stimulus comprises 10 videos showing object state changes (e.g., ice melting). During playing, the video would stop and immediately be obscured by mosaics at a specific point. Participants select from three detection images (the exact frame of the video just be masked, the frame after that, and the frame before that) to test representational momentum and estimate the duration of the video in seconds to test time perception. The depressive group showed diminished representational momentum (i.e., lower scores on the task of representational momentum) than normal controls (U = 215.00, Z = -5.83, p < 0.001). In addition, the scores on the task of representational momentum were significantly positively related with the scores on the task of time perception among depressive group (r = 0.446, p = 0.004). The findings indicate that patients with depressive disorder may exhibit diminished representational momentum for physical states, which may be correlated with their impairment of time perception.

Effect of Tranexamic Acid on Hidden Blood Loss in Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion: A Retrospective Study.

Purpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss. Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events. Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group. Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.

Unraveling the relationship between serum parathyroid hormone levels and trabecular bone score: a cross-sectional study.

The TBS is a new method for clinicians to assess the bone quality. It is directly related to the mechanical strength of bone and helps predict fracture risk. The present analysis aimed to investigate the associations between serum PTH levels and TBS by analyzing data from the National Health and Nutrition Examination Survey (NHANES). A total of 3516 participants from the NHANES 2005-2006 were included in this cross-sectional study. The independent variable was serum PTH, and the outcome variable was TBS. The associations of serum PTH levels with TBS were examined using multivariable linear regression models. After adjusting for covariates, there was a negative association between serum PTH level and TBS (ß = - 0.0034; 95% confidence interval, - 0.0050 to - 0.0017). However, in the subgroup analysis stratified by gender, race, and age, this association became negative only in Non-Hispanic White (ß = - 0.0047, 95% CI: -  0.0071 to -  0.0048) and young people (age < 60) (ß = - 0.0036, 95% CI: - 0.0057, - 0.0016), regardless of gender. In addition, the association of serum PTH with TBS was an U-shaped curve, with a point of inflection at 6.71 pmol/L. This study showed that serum PTH level was negatively associated with TBS. Maintaining PTH levels in a lower reasonable clinical range may be beneficial to bone health, especially for young non-Hispanic white.

The genetic causal association between hip or knee osteoarthritis and frailty: a two-sample Mendelian randomization analysis.

Introduction: Osteoarthritis of the hip or knee has been reported to be linked to an increased risk of frailty. However, a definitive conclusion about whether hip or knee osteoarthritis increases susceptibility to frailty remains elusive. Material and methods: The instrumental variables (IVs) used in this analysis were sourced from publicly available genome-wide association study (GWAS) datasets. We used a two-sample Mendelian randomization analysis to evaluate the plausible causal nexus between hip or knee osteoarthritis and frailty. Results: We included a total of 25 single-nucleotide polymorphisms (SNPs) as instrumental variables through rigorous and comprehensive screening. The results of this analysis suggested that hip or knee osteoarthritis is associated with an elevated risk of frailty. These results remained robust and consistent across multiple calculation methods, including inverse variance weighted (OR = 1.082, 95% CI: 1.0532-1.1125, p = 1.36 × 10-8), MR-Egger regression (OR = 1.175, 95% CI: 1.0162-1.3604, p = 0.040), weighted median estimation (OR = 1.078, 95% CI: 1.0365-1.1219, p = 1.831 × 10-4), weighted mode analysis (OR = 1.089, 95% CI: 1.0078-1.1771, p = 0.041) and simple mode analysis (OR = 1.093, 95% CI: 1.0112-1.1830, p = 0.034). Cochran's Q test showed no evidence of heterogeneity among the IV estimates derived from individual variants, and the MR-Egger regression analysis indicated that the presence of horizontal pleiotropy was unlikely to introduce bias into the results (intercept: -0.0044, p = 0.549). Conclusions: Two-sample Mendelian randomization analysis effectively identified hip or knee osteoarthritis as a contributing risk factor for frailty.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis.

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

Deficit of theory of mind after temporal lobe cerebral infarction.

BACKGROUND: Previous studies have indicated that the temporal lobe is involved in theory of mind (ToM). However, little attention has been paid to ToM in patients with cerebral infarction. In this study, we investigated the ability of ToM in patients with temporal lobe cerebral infarction (TLCI) using a variety of tests. METHODS: In the study, 19 patients with TLCI and 20 healthy controls (HC) were examined using the Recognition of faux pas and the Reading the Mind in the Eyes (RME) tasks, to assess their ability of ToM. RESULTS: The results of the study indicated that the TLCI group performed significantly worse compared with the HC group as revealed in the total faux pas-related score and in emotion recognition (Mind Reading). CONCLUSIONS: Our results implied that patients with TLCI had difficulty in ToM. Our data provided new evidence that the temporal lobe may be involved in processing ToM inferences.

Chlorine dioxide inactivation of enterovirus 71 in water and its impact on genomic targets.

To control the waterborne transmission of enterovirus 71(EV71), which is associated with hand foot and mouth disease (HFMD), it is essential to know the inactivation effectiveness of disinfectants on EV71 in water. In this article, we present a comparative analysis of the effects on EV71 following exposure to chlorine dioxide (ClO2) under different doses, pH, and temperature conditions. We show that the EV71 exhibited strong resistance to ClO2 (more than the MS2 standard) and that Ct value ranges required for a 4-log reduction of EV71 in buffered, disinfectant demand-free water at pH 7.2 and 20 °C by ClO2 were 4.24-6.62 mg/L·min according to the efficiency factor Hom model. ClO2 inactivation of the virus was temperature- and pH-dependent. The virucidal efficiency was higher at pH 8.2 than at pH 5.6 and pH 7.2 and higher at 36 °C than at 4 and 20 °C. In addition, we also observed the impact of ClO2 on the entire viral genome using RT-PCR, which indicated that the 5' noncoding region (5'-NCR) within the EV71 genome, specifically the 1-118 nt region, was the most easily damaged by ClO2 and correlated with viral infectivity. Our study has not only provided guidelines for EV71 disinfection strategies of waste and drinking water, but also confirmed the importance of the 5'-NCR for EV71 infectivity and may demonstrate a general inactivation by ClO2 of enteric virus by damaging the 5'-NCR. Furthermore, 5'-NCR can be used as a target region for PCR to investigate infectious virus contamination in environmental water and evaluate the inactivation effects of ClO2.

Dissociation of understanding from applying others' false beliefs in remitted schizophrenia: evidence from a computerized referential communication task.

BACKGROUND: In research on theory of mind (ToM), false belief paradigms are commonly used. Previous studies have reported that there is heterogeneity in the magnitude of impairment on false belief tasks. Moreover, intact ability to attribute others' false beliefs has been widely reported in patients with remitted schizophrenia. Increasingly, evidence suggests that there may be different cognitive mechanisms underlying the understanding others' false beliefs versus applying one's knowledge of others' false beliefs. Since the role of psychotic symptoms in ToM impairments is an important issue in the study of ToM deficits in schizophrenia, we examined both remitted schizophrenia and non-remitted schizophrenia, with the aim to investigate whether psychotic symptoms in schizophrenia are associated with deficits in understanding others' mental states or difficulties in applying this understanding. METHODS: The present study investigated 29 patients with non-remitted schizophrenia, 19 patients with remitted schizophrenia, and 22 healthy controls with a revised computerized referential communication task. The ability to understand others' false beliefs and the ability to apply others' false beliefs were measured separately. RESULTS: Patients with non-remitted schizophrenia performed significantly worse than patients with remitted schizophrenia and healthy controls on a task of understanding others' false beliefs, whereas no significant difference was found between the patients with remitted schizophrenia and healthy controls. Both the patients with non-remitted schizophrenia and patients with remitted schizophrenia performed significantly worse than healthy controls on a task of applying others' false beliefs. CONCLUSIONS: Our findings suggested a dissociation of understanding others' false beliefs from applying others' false beliefs in remitted schizophrenia. We preliminarily conclude that deficits in the ToM ability of applying knowledge of others' mental states might be state-dependent.

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition.

Katsumadain A, a naturally occurring influenza virus neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner-Wadsworth-Emmons/oxa Michael addition.