Establishment and verification of a nomogram that predicts the risk for coronary slow flow.

Background: Coronary slow flow (CSF) has gained significance as a chronic coronary artery disease, but few studies have integrated both biological and anatomical factors for CSF assessment. This study aimed to develop and validate a simple-to-use nomogram for predicting CSF risk by combining biological and anatomical factors. Methods: In this retrospective case-control study, 1042 patients (614 CSF cases and 428 controls) were randomly assigned to the development and validation cohorts at a 7:3 ratio. Potential predictive factors were identified using least absolute shrinkage and selection operator regression and subsequently utilized in multivariate logistic regression to construct the nomogram. Validation of the nomogram was assessed by discrimination and calibration. Results: N-terminal pro brain natriuretic peptide, high density lipoprotein cholesterol, hemoglobin, left anterior descending artery diameter, left circumflex artery diameter, and right coronary artery diameter were independent predictors of CSF. The model displayed high discrimination in the development and validation cohorts (C-index 0.771, 95% CI: 0.737-0.805 and 0.805, 95% CI: 0.757-0.853, respectively). The calibration curves for both cohorts showed close alignment between predicted and actual risk estimates, demonstrating improved model calibration. Decision curve analysis suggested high clinical utility for the predictive nomogram. Conclusion: The constructed nomogram accurately and individually predicts the risk of CSF for patients with suspected CSF and may be considered for use in clinical care.

Major Adverse Cardiovascular Events and Prognosis in Patients With Coronary Slow Flow.

This study aimed to investigate its clinical implications, risk factors, prognosis, and overall long-term outcomes. Demographic profiles, various clinical characteristics, and clinical outcomes were compared between 614 patients with coronary slow flow (CSF) and 428 patients with normal coronary artery. The incidence of CSF was found to be 2.65%. Significant differences were observed between patients with CSF and control subjects in terms of sex, chest tightness, hyperlipidemia, smoking history, alcohol consumption, age, height, weight, body mass index, diastolic blood pressure, heart rate, and body surface area (P < 0.05). CSF (hazard ratio: 1.531; 95% confidence interval: 1.064-2.202; p = 0.022) proved to be independent prognostic predictors of major adverse cardiovascular events (MACEs). Kaplan-Meier survival evaluations for MACEs presented a worser outcome for patients with CSF. Patients with CSF are at high risk for cardiovascular events and experience generally poor clinical outcomes.

Habenula functional connectivity variability increases with disease severity in individuals with major depression.

BACKGROUND: Increasing evidence has suggested the significant relationships between major depressive disorder (MDD) and the neural abnormalities of the Habenula (Hb). Yet, previous research on the relationships between Hb and MDD mainly focuses on the static descriptions of their functional connectivity. However, recent work suggests that the connectivity patterns are indeed dynamic, though related analysis and interpretation remain scarce. METHODS: Using seed-based resting-state fMRI, the static (sFC) and dynamic functional connectivity (dFC) between the Hb and whole-brain were calculated, including 51 clinical participants (MDDs) and 45 healthy controls (HCs). Association between the aberrant connectivity patterns and depressive symptomatology was also analyzed. RESULTS: Compared with the HCs, MDDs exhibited increased sFC from the left Hb to the right inferior temporal gyrus and left superior frontal gyrus (SFG), while sFC to the right calcarine gyrus decreased. Notably, we observed that dFC between the left Hb and the right supplementary motor area, right postcentral gyrus (PoCG), left inferior frontal gyrus as well as left occipital gyrus was weak in MDDs. Furthermore, sFC between the Hb and SFG correlated positively with the measured attention-related cognitive deficits. Importantly, there was a positive correlation between dFC between the Hb and PoCG and depressive severity. CONCLUSIONS: The findings indicate that the anomalous neural circuitry of Hb may underpin impaired attention disengagement, emotional modulation and motor inhibition associated with depressive symptoms such as rumination disposition and psychomotor retardation. This may open new avenues for studying the neuropathology mechanisms and guiding new treatment strategies for MDD.

Machine learning-based combined nomogram for predicting the risk of pulmonary invasive fungal infection in severely immunocompromised patients.

Background: Early and accurate diagnosis of invasive fungal infection (IFI) is pivotal for the initiation of effective antifungal therapy for patients with hematologic malignancies. Methods: This retrospective study involved 235 patients with hematologic malignancies and pulmonary infections diagnosed as IFIs (n=118) or bacterial pneumonia (n=117). Patients were randomly divided into training (n=188) and validation (n=47) datasets. Four feature selection methods with nine classifiers were implemented to select the optimal machine learning (ML) model using five-fold cross-validation. A radiomic signature was constructed using a linear ML algorithm, and a radiomic score (Radscore) was calculated. The combined model was developed with the Radscore, the significant clinical and radiologic factors were selected using multivariable logistic regression, and the results were presented as a clinical radiomic nomogram. A prospective pilot study was also conducted to compare the classification performance of the combined nomogram with practicing radiologists. Results: Significant differences were found in the Radscore between IFI and bacterial pneumonia patients in the training (0.683 vs. -0.724, P<0.001) and validation set (0.353 vs. -0.717, P=0.002). The combined model showed good discrimination performance in the validation cohort [area under the curve (AUC) =0.844] and outperformed the clinical (AUC =0.696) and radiomics (AUC =0.767) model alone (both P<0.05). Conclusions: The clinical radiomic nomogram can serve as a promising predictive tool for IFI in patients with hematologic malignancies.

Adding CuCo2O4-GO to inhibit bromate formation and enhance sulfamethoxazole degradation during the ozone/peroxymonosulfate process: Efficiency and mechanism.

In this work, a new type of catalyst CuCo2O4-GO was synthesized as a heterogeneous catalyst, and its control effect on bromate (BrO3-)generation and sulfamethoxazole (SMX) degradation in O3/PMS process was studied. When 100 mg/L CuCo2O4-GO was added to the reaction system, the BrO3- concentration generated was 0.25 µM at pH = 7.0, 100 µM PMS addition and 1.30 mg/min ozone injection after 30 min reaction. Compared with the 6.58 µM BrO3- produced in the control group, the addition of CuCo2O4-GO prominently inhibited the generation of BrO3- and the inhibition efficiency reached 96.17 %. The addition of CuCo2O4-GO inhibited the conversion of hypobromous acid, thereby inhibiting the formation of BrO3-. Meanwhile, the first-order kinetic constant of the degradation of SMX by O3/PMS and O3/PMS/CuCo2O4-GO was 0.163 and 0.422 min-1, respectively. The addition of CuCo2O4-GO promoted the degradation of SMX and the removal efficiency was reached above 98 % after 10 min reaction. According to the optimization of the GO loading ratio, it was found that CuCo2O4-GO with 20 % GO loading had the best promotion effect on the degradation of SMX, and almost completely inhibited the formation of BrO3-. Finally, in the repeated cycle experiment, CuCo2O4-GO could maintain its high catalytic activity and still had a high removal effect on SMX after three repeated uses. Besides, the BrO3- inhibition efficiency was above 80 % after two repeated uses. Therefore, adding synthetic CuCo2O4-GO is an effective way to control the formation of BrO3- and enhance the degradation of SMX in the O3/PMS process.

Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides.

This article describes studies on the regioselective acetal protection of monosaccharide-based diols using chiral phosphoric acids (CPAs) and their immobilized polymeric variants, (R)-Ad-TRIP-PS and (S)-SPINOL-PS, as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various d-glucose-, d-galactose-, d-mannose-, and l-fucose-derived 1,2-diols and could be carried out in a regiodivergent fashion depending on the choice of chiral catalyst. The polymeric catalysts were conveniently recycled and reused multiple times for gram-scale functionalizations with catalytic loadings as low as 0.1 mol %, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 32 regioisomerically pure differentially protected mono- and disaccharide derivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (R)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected d-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated substrates revealed that low-temperature acetalizations happen via a syn-addition mechanism and that the reaction regioselectivity exhibits strong dependence on the temperature. The computational studies indicate a complex temperature-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and another via concerted asynchronous formation of an acetal, that results in syn-addition products. The computational models also explain the steric factors responsible for the observed C2 selectivities and are consistent with experimentally observed selectivity trends.

Experimental and Computational Studies on Regiodivergent Chiral Phosphoric Acid Catalyzed Cycloisomerization of Mupirocin Methyl Ester.

This article presents a new strategy for achieving regiocontrol over the endo versus exo modes of cycloisomerizations of epoxide-containing alcohols, which leads to the formation of five- or six-membered cyclic ethers. Unlike traditional methods relying on achiral reagents or enzymes, this approach utilizes chiral phosphoric acids to catalyze the regiodivergent selective formations of either tetrahydrofuran- or tetrahydropyran-containing products. By using methyl ester of epoxide-containing antibiotic mupirocin as the substrate, it is demonstrated that catalytic chiral phosphoric acids (R)-TCYP and (S)-TIPSY could be used to achieve the selective formation of either the six-membered endo product (95:5 r.r.) or the five-membered exo product (77:23 r.r.), correspondingly. This cyclization was found to be unselective under the standard conditions involving various achiral acids, bases, or buffers. The subsequent mechanistic studies using state-of-the-art quantum chemical solutions provided the description of the potential energy surface, which is fully consistent with the experimental observations. Based on these results, highly detailed reaction paths are obtained and a concerted and highly synchronous mechanism is proposed for the formation of both exo and endo products.

Regioselective single pot C3-glycosylation of strophanthidol using methylboronic acid as a transient protecting group.

This manuscript describes a single pot protocol for the selective introduction of unprotected sugars to the C3 position of the cardiotonic steroid strophanthidol. These reactions proceed with high levels of regiocontrol (>20:1 rr) in the presence of three other hydroxyl functionalities including the C19 primary hydroxyl group and could be applied to different sugars to provide the deprotected cardiac glycosides upon work up (5 examples, 77-69% yield per single operation). The selective glycosylation of the less reactive C3 position is accomplished by the use of traceless protection with methylboronic acid that blocks the C5 and C19 hydroxyls by forming a cyclic boronic ester, followed by in situ glycosylation and a work up with ammonia in methanol to remove the boronic ester and the carbohydrate ester protecting groups.

Copper(II)-Catalyzed Tandem Decarboxylative Michael/Aldol Reactions Leading to the Formation of Functionalized Cyclohexenones.

This work describes the development of a new single-pot copper(II)-catalyzed decarboxylative Michael reaction between ß-keto acids and enones, followed by in situ aldolization, which results in highly functionalized chiral and achiral cyclohexenones. The achiral version of this Robinson annulation features a hitherto unprecedented Michael reaction of ß-keto acids with sterically hindered ß,ß'-substituted enones and provides access to all carbon quaternary stereocenter-containing cyclohexenones (11 examples, 43-83% yield). In addition, an asymmetric chiral bis(oxazoline) copper(II)-catalyzed single-pot Robinson annulation has been devised for preparing chiral cyclohexenones, including some products that contain vicinal stereocenters (5 examples, 65-85% yield, 84-94% ee). This latter protocol has been successfully applied to the enantioselective formation of the oxygenated 10-nor-steroid core from readily available starting materials.