Maximum likelihood estimation for semiparametric regression models with interval-censored multistate data.

Interval-censored multistate data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We relate potentially time-dependent covariates to multistate processes through semiparametric proportional intensity models with random effects. We study nonparametric maximum likelihood estimation under general interval censoring and develop a stable expectation-maximization algorithm. We show that the resulting parameter estimators are consistent and that the finite-dimensional components are asymptotically normal with a covariance matrix that attains the semiparametric efficiency bound and can be consistently estimated through profile likelihood. In addition, we demonstrate through extensive simulation studies that the proposed numerical and inferential procedures perform well in realistic settings. Finally, we provide an application to a major epidemiologic cohort study.

Efficacy of Low-Dose Scopolamine and Palonosetron in Reducing Immediate Post-Gastrointestinal Endoscopy Nausea and Vomiting: A Prospective, Randomized, Controlled Study.

This study aimed to assess the incidence of post-discharge nausea and vomiting (PDNV) following sedation with nalbuphine and etomidate and to evaluate the prophylactic effects of scopolamine in reducing PDNV. A two-stage prospective clinical trial was conducted. The first part involved an observational study of 77 subjects to assess the PDNV incidence post-sedation with nalbuphine, etomidate, and propofol. The second part compared the effectiveness of palonosetron 0.075 mg (P group), scopolamine 0.1 mg (S group), and their combination (PS group) in reducing PDNV. The primary endpoint was the incidence of PDNV within 8 h post-sedation. Secondary outcomes included PDNV frequency and severity at 8-24, 0-24, and 24-48 h and side effects of medications. The incidence of PDNV within 8 h post-sedation was 37.66% (29/77). The PS group showed a significantly lower PDNV rate of 2.56% within 8 h, compared to the P group (35.71%, P < .001), S group (19.64%, P < .001), and control group (38.39%, P < .001), respectively. The S group (19.64%) also had a lower rate than the P group (35.71%, P = .007) and the control group (38.39%, P = .002). Subgroup analysis suggested a potential differential effect of palonosetron in reducing vomiting among male patients undergoing gastrointestinal procedures. The combination therapy was also associated with fewer cases of mild or no nausea and vomiting. In summary, the incidence of PDNV following sedation with nalbuphine and etomidate was notably high. The combination of scopolamine and palonosetron was more effective in preventing PDNV, with implications for improved post-sedation care.

Changes in Intrinsically Photosensitive Retinal Ganglion Cells, Dopaminergic Amacrine Cells, and Their Connectivity in the Retinas of Lid Suture Myopia.

Purpose: This study investigates alterations in intrinsically photosensitive retinal ganglion cells (ipRGCs) and dopaminergic amacrine cells (DACs) in lid suture myopia (LSM) rats. Methods: LSM was induced in rats by suturing the right eyes for 4 weeks. Double immunofluorescence staining of ipRGCs and DACs in whole-mount retinas was performed to analyze changes in the density and morphology of control, LSM, and fellow eyes. Real-time quantitative PCR and Western blotting were used to detect related genes and protein expression levels. Results: Significant myopia was induced in the lid-sutured eye, but the fellow eye was not different to control. Decreased ipRGC density with paradoxically increased overall melanopsin expression and enlarged dendritic beads was observed in both the LSM and fellow eyes of the LSM rat retinas. In contrast, DAC changes occurred only in the LSM eyes, with reduced DAC density and tyrosine hydroxylase (TH) expression, sparser dendritic processes, and fewer varicosities. Interestingly, contacts between ipRGCs and DACs in the inner plexiform layer (IPL) and the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and vesicular monoamine transporter protein 2 (VMAT2) mRNA were decreased in the LSM eyes. Conclusions: The ipRGCs and DACs in LSM rat retinas undergo multiple alterations in density, morphology, and related molecule expressions. However, the ipRGC changes alone appear not to be required for the development of myopia, given that myopia is only induced in the lid-sutured eye, and they are unlikely alone to drive the DAC changes. Reduced contacts between ipRGCs and DACs in the LSM eyes may be the structural foundation for the impaired signaling between them. PACAP and VMAT2, strongly associated with ipRGCs and DACs, may play important roles in LSM through complex mechanisms.

Servant leadership and employee voice behavior: the role of employee work reflection and employee proactive personality.

Despite the recent proliferation of scholarly investigations on servant leadership, clarity remains elusive regarding the specific mechanisms and conditions underpinning employee cognitive processes and their responses to servant leadership. Drawing upon social cognitive theory, proposes a moderated mediation model tested through a time-lagged field data from 489 employees in Study 1 and an experimental data in Study 2. We found that servant leadership indirectly enhances employee voice behavior through increased employee work reflection. Additionally, we considered employee proactive personality as a boundary condition for the positive effect of servant leadership. Our results show that servant leadership prompts employee work reflection only when the level of employee proactive personality is high, which in turn increases employee voice behavior. This study presents significant theoretical and practical implications through the integration of social cognitive theory with servant leadership research.

Comprehensive Transcriptome Analysis Expands lncRNA Functional Profiles in Breast Cancer.

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention.

Clinicopathological characteristics and oncologic outcomes of patients with gestational trophoblastic neoplasia manifesting as isolated pulmonary lesions.

OBJECTIVE: To elucidate the clinicopathological characteristics and oncological outcomes of a special group of patients with gestational trophoblastic neoplasia (GTN) initially presenting with isolated lung lesions, elevated human chorionic gonadotropin (hCG) levels, and unobserved pelvic lesions. METHODS: Overall, 2358 patients with GTN treated at our hospital between 2000 and 2023 were retrospectively reviewed, and 40 patients were evaluated. The demographic characteristics, clinicopathological features, treatment data, and follow-up information of each patient were collected. The primary outcome was progression free survival. Kaplan-Meier analysis and univariate and multivariate Cox proportional hazard analyses were used to identify the risk factors. RESULTS: Among the 40 patients, 95.0 % had solitary lung lesions, with a median size of 1.9 cm. Moreover, 72.5 % of patients were pathologically confirmed as epithelioid trophoblastic tumors (ETT). During a median follow-up period of 53.5 months (range, 2-143), 11 patients experienced recurrence, including all patients who received chemotherapy alone as the initial treatment, and no death was observed. Relapse treatment involved lung segmentectomy and lobectomy combined with chemotherapy and immunotherapy. Univariate and multivariate Cox analyses identified comparing with surgery±chemotherapy, chemotherapy alone as the initial treatment (hazard ratio [HR] =7.738, 95 % confidence interval [CI] 1.698-35.269, P = 0.008) as independent risk factor for recurrence. CONCLUSIONS: In patients with a history of pregnancy exhibiting isolated pulmonary lesions, elevated hCG levels (mostly <1000 mIU/mL), and unobserved pelvic lesions, ETT should be considered first. Surgical resection of lung lesion is crucial for optimal management. When chemotherapy is considered, multidrug regimen is recommended.

Kinetic understanding of lithium metal electrodeposition for lithium anodes.

Lithium, a representative alkali metal, holds the coveted status of the "holy grail" in the realm of next-generation rechargeable batteries, owing to its remarkable theoretical specific capacity and low electrode potential. However, the inherent reactivity of Li metal inevitably results in the formation of the solid-electrolyte interphase (SEI) on its surface, adding complexity to the Li electrodeposition process compared to conventional metal electrodeposition. Attaining uniform Li deposition is crucial for ensuring stable, long-cycle performance and high Coulombic efficiency in Li metal batteries, which requires a comprehensive understanding of the underlying factors governing the electrodeposition process. This review delves into the intricate kinetics of Li electrodeposition, elucidating the multifaceted factors that influence charge and mass transfer kinetics. The intrinsic relationship between charge transfer kinetics and Li deposition is scrutinized, exploring how parameters such as current density and electrode potential impact Li nucleation and growth, as well as dendrite formation. Additionally, the applicability of classical mass-transfer-controlled electrodeposition models to Li anode systems is evaluated, considering the influence of ionic concentration and solvation structure on Li+ transport, SEI formation, and subsequent deposition kinetics. The pivotal role of SEI compositional structure and physicochemical properties in governing charge and mass transfer processes is underscored, with an emphasis on strategies for regulating Li deposition kinetics from both electrolyte and SEI perspectives. Finally, future directions in Li electrodeposition research are outlined, emphasizing the importance of ongoing exploration from a kinetic standpoint to fully unlock the potential of Li metal batteries.

Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

PURPOSE: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A-rearranged (KMT2Ar) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia. METHODS: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 (NPM1) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar. The separate NPM1 cohort of the trial is ongoing. RESULTS: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% (P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease. CONCLUSION: Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.

IL-2-armored peptide-major histocompatibility class I bispecific antibodies redirect antiviral effector memory CD8+ T cells to induce potent anti-cancer cytotoxic activity with limited cytokine release.

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

Multi-disease X-ray Image Classification of the Chest Based on Global and Local Fusion Adaptive Networks.

BACKGROUND: Chest X-ray image classification for multiple diseases is an important research direction in the field of computer vision and medical image processing. It aims to utilize advanced image processing techniques and deep learning algorithms to automatically analyze and identify X-ray images, determining whether specific pathologies or structural abnormalities exist in the images. OBJECTIVE: We present the MMPDenseNet network designed specifically for chest multi-label disease classification. METHODS: Initially, the network employs the adaptive activation function Meta-ACON to enhance feature representation. Subsequently, the network incorporates a multi-head self-attention mechanism, merging the conventional convolutional neural network with the Transformer, thereby bolstering the ability to extract both local and global features. Ultimately, the network integrates a pyramid squeeze attention module to capture spatial information and enrich the feature space. RESULTS: The concluding experiment yielded an average AUC of 0.898, marking an average accuracy improvement of 0.6% over the baseline model. When compared with the original network, the experimental results highlight that MMPDenseNet considerably elevates the classification accuracy of various chest diseases. CONCLUSION: It can be concluded that the network, thus, holds substantial value for clinical applications.

Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

Phase Transformation and Mechanical Behaviour of Different Heat-Treated Nickel-Titanium Rotary Instruments.

OBJECTIVES: This study evaluated the phase composition, phase transformation behaviour, and mechanical properties of five heat-treated NiTi instruments. METHODS: ProTaper NEXT (M-wire, PTN), ProTaper Gold (Gold-wire, PTG), One Curve (C-wire, OC), EdgeTaper Platinum (Fire-wire, ETP), NeoNiTi (electrical discharge machining-wire, NNA), and ProTaper Universal (conventional wire, PTU, control) with #25-tip size were tested (n = 12/group) for cyclic fatigue resistance (number of cycles to failure; NCF) and torsional resistance (angle of rotation to fracture and maximum torque at fracture [ultimate torsional strength]). The geometry and fracture surfaces of the tested instruments were examined by scanning electron microscopy. The phase transformation temperature and phase composition of the instruments were evaluated using differential scanning calorimetry and X-ray diffraction. Data were statistically analysed using one-way ANOVA and Tukey's post hoc test, with the significance level set at 5%. RESULTS: PTG showed the highest NCF (P < .05) at 37°C, while ETP exhibited the highest angle of rotation to fracture, ultimate torsional strength, and stiffness (P < .05). Scanning electron microscopy demonstrated typical clusters of fatigue striations and numerous cracks after cyclic fatigue fracture, whereas there was a concentric abrasion pattern with a dimple and microvoids at the centre after torsional fracture. In differential scanning calorimetry curves, austenite-finishing temperatures of heat-treated instruments were higher than 37°C, whereas that of PTU was lower than 37°C. PTU showed strong peaks of austenite at 25 and 37°C, whereas ETP showed a strong peak of R-phase at 25°C, but mostly austenite phase at 37°C in X-ray diffraction. CONCLUSIONS: Geometry, alloy type, and phase transformation temperatures of NiTi instruments affected their mechanical behaviour. CLINICAL RELEVANCE: PTG showed the highest NCF, suitable for markedly curved canals. ETP had the highest torsional resistance, appropriate for narrow and constricted canals.

Making Rift Valley Fever Viral Particles Fluorescent.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that represents a significant threat to both human and veterinary public health. Since its discovery in the Great Rift Valley of Kenya in the 1930s, the virus has spread across Africa and beyond, now posing a risk of introduction into Southern Europe and Asia. Despite recent progresses, early RVFV-host cell interactions remain largely uncharacterized. In this method chapter, we delineate the procedure for labeling RVFV particles with fluorescent organic dyes. This approach makes it feasible to visualize single viral particles in both fixed and living cells and study RVFV entry into host cells. We provide additional examples with two viruses closely related to RVFV, namely, Toscana virus and Uukuniemi virus. Furthermore, we illustrate how to utilize fluorescent viral particles to examine and quantify each step of the cell entry program of RVFV, which includes state-of-the-art fluorescence-based detection techniques such as fluorescence microscopy, flow cytometry, and fluorimetry.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

NMR-Based Chiral Discrimination of Bulky Amines with a 19F-Tagged NNO Pincer Complex.

Within pharmaceutical research, ensuring the enantiomeric purity of chiral compounds is critical. Specifically, chiral amines are a crucial category of compounds, due to their extensive therapeutic uses. However, the enantiomeric analysis of these compounds, particularly those with significant steric hindrance, remains a challenge. To address this issue, our research introduces a novel chiral 19F-tagged NNO palladium pincer probe, strategically engineered with an open binding site to accommodate bulky amines. This probe facilitates the enantiodifferentiation of such amines, as evidenced by the distinct 19F NMR signals generated by the enantiomers. Moreover, our findings highlight the probe's applicability in the chiral discrimination of various psychoactive substances, underscoring its potential for the identification of illegal stimulant use and contributing to forensic investigations.

[Analysis of clinical features and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency].

OBJECTIVE: To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ). METHODS: Clinical data of three children diagnosed with late-onset MADD at the Children's Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years. RESULTS: The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c.1211T>C (p.M404T) and a maternal c.488-22T>G variant in child 1, a paternal c.1717C>T (p.Q573X) and a maternal c.250G>A (p.A84T) variant in child 2, and a paternal c.1285+1G>A and maternal c.629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. CONCLUSION: The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Unraveling the energy storage mechanism in graphene-based nonaqueous electrochemical capacitors by gap-enhanced Raman spectroscopy.

Graphene has been extensively utilized as an electrode material for nonaqueous electrochemical capacitors. However, a comprehensive understanding of the charging mechanism and ion arrangement at the graphene/electrolyte interface remain elusive. Herein, a gap-enhanced Raman spectroscopic strategy is designed to characterize the dynamic interfacial process of graphene with an adjustable number of layers, which is based on synergistic enhancement of localized surface plasmons from shell-isolated nanoparticles and a metal substrate. By employing such a strategy combined with complementary characterization techniques, we study the potential-dependent configuration of adsorbed ions and capacitance curves for graphene based on the number of layers. As the number of layers increases, the properties of graphene transform from a metalloid nature to graphite-like behavior. The charging mechanism shifts from co-ion desorption in single-layer graphene to ion exchange domination in few-layer graphene. The increase in area specific capacitance from 64 to 145 µF cm-2 is attributed to the influence on ion packing, thereby impacting the electrochemical performance. Furthermore, the potential-dependent coordination structure of lithium bis(fluorosulfonyl) imide in tetraglyme ([Li(G4)][FSI]) at graphene/electrolyte interface is revealed. This work adds to the understanding of graphene interfaces with distinct properties, offering insights for optimization of electrochemical capacitors.

The association between TLR2/4 and clinical outcome in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Toll-like receptors (TLRs) are involved in innate immunity and inflammatory responses in various diseases. Our study aimed to investigate the association between the levels of soluble TLR4 (sTLR4) and soluble TLR2 (sTLR2) and clinical outcomes following intracerebral hemorrhage (ICH). METHODS: Patients admitted to department of Neurology with acute ICH were included. Plasma levels of sTLR4 and sTLR2 after ICH were measured by enzyme-linked immunosorbent assay. Poor clinical outcome was defined as a modified Rankin score (mRS) of 3-6 at 3-month and 12-month after onset. RESULTS: All 207 patients with ICH and 100 non-stroke controls were included in our analysis. The mean sTLR4 level was 4.53±1.51 ng/ml and mean sTLR2 level was 3.65±0.72 ng/ml. There was significant trend towards worse clinical outcomes with increasing sTLR4 and sTLR2 terciles at 3 and 12 months. According to receiver operating curve (ROC), the sTLR4 was reliable predictor for poor clinical outcome at 3 months (ROC=0.75) and 12 months (ROC=0.74). The sTLR2 was less reliable predictor for poor clinical outcome at 3 months (ROC=0.64) and 12 months (ROC=0.65). The level of sTLR4 was an independent predictor of poor clinical outcome at 12-month (OR 1.24, 95 % CI 1.16-1.80; P=0.019). CONCLUSIONS: The sTLR4 quantification may provide accurate prognostic information after ICH.

Modular access to diarylmethyl sulfonamides via visible light-promoted cross-coupling reactions.

We report a novel and efficient method for the preparation of diarylmethyl sulfonamide derivatives through visible-light-induced sulfamoylation of para-quinone methides with sulfamoyl chlorides under mild, metal-free conditions. This protocol demonstrates excellent tolerance toward a wide range of functional groups, affording the corresponding products in moderate to high yields. Preliminary mechanism studies revealed that the excited photocatalyst rhodamine 6G* was mainly quenched by para-quinone methides and the generated diarylmethyl radical intermediates then underwent radical-radical cross-coupling with sulfamoyl radicals to yield the diarylmethyl sulfonamides.

Low-Dispersity Polymers via Free Radical Alternating Copolymerization: Effects of Charge-Transfer-Complexes.

Alternating copolymers are crucial for diverse applications. While dispersity (Ɖ, also known as molecular weight distribution, MWD) influences the properties of polymers, achieving low dispersities in alternating copolymers poses a notable challenge via free radical polymerizations (FRPs). In this work, we demonstrated an unexpected discovery that dispersities are affected by the participation of charge transfer complexes (CTCs) formed between monomer pairs during free radical alternating copolymerization, which have inspired the successful synthesis of various alternating copolymers with low dispersities (>30 examples, Ɖ = 1.13-1.39) under visible-light irradiation. The synthetic method is compatible with binary, ternary and quaternary alternating copolymerizations and is expandable for both fluorinated and non-fluorinated monomer pairs. DFT calculations combined with model experiments indicated that CTC-absent reaction exhibits higher propagation rates and affords fewer radical terminations, which could contribute to low dispersities. Based on the integration of Monte Carlo simulation and Bayesian optimization, we established the relationship map between FRP parameter space and dispersity, further suggested the correlation between low dispersities and higher propagation rates. Our research sheds light on dispersity control via FRPs and creates a novel platform to investigate polymer dispersity through machine learning.