Giant optical second- and third-order nonlinearities at a telecom wavelength.

A material platform that excels in both optical second- and third-order nonlinearities at a telecom wavelength is theoretically and experimentally demonstrated. In this TiN-based coupled metallic quantum well structure, electronic subbands are engineered to support doubly resonant inter-subband transitions for an exceptionally high second-order nonlinearity and provide single-photon transitions for a remarkable third-order nonlinearity within the 1400-1600 nm bandwidth. The second-order susceptibility χ(2) reaches 2840 pm/V at 1440 nm, while the Kerr coefficient n2 arrives at 2.8 × 10-10 cm2/W at 1460 nm. The achievement of simultaneous strong second- and third-order nonlinearities in one material at a telecom wavelength creates opportunities for multi-functional advanced applications in the field of nonlinear optics.

Partial coil embolization before surgical clipping of ruptured intracranial aneurysms.

OBJECTIVE: Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR. METHODS: We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination. RESULTS: We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95-8.7] vs. 4.6 mm [3.3-6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4%, vs. 30/73, 41%; P = 0.001). Inpatient mortality was 14.8% (4/27) in patients with partially-embolized aneurysms and 28.8% (21/73) in patients without embolization (P = 0.20). Discharge to home or inpatient rehabilitation was 74.0% in patients with partially-embolized aneurysms and 56.2% in patients without embolization (P = 0.11). A complication from partial embolization occurred in 2/27 (7.4%) patients. CONCLUSIONS: Preoperative partial endovascular coil embolization of ruptured aneurysms is associated with a reduced frequency of IOR during definitive treatment with surgical clip obliteration. These results and the impact of preoperative partial endovascular coil embolization on functional outcomes should be confirmed with a randomized trial.

Improving cancer immunotherapy in prostate cancer by modulating T cell function through targeting the galectin-1.

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.

ENCAP: Computational prediction of tumor T cell antigens with ensemble classifiers and diverse sequence features.

Cancer immunotherapy enhances the body's natural immune system to combat cancer, offering the advantage of lowered side effects compared to traditional treatments because of its high selectivity and efficacy. Utilizing computational methods to identify tumor T cell antigens (TTCAs) is valuable in unraveling the biological mechanisms and enhancing the effectiveness of immunotherapy. In this study, we present ENCAP, a predictor for TTCA based on ensemble classifiers and diverse sequence features. Sequences were encoded as a feature vector of 4349 entries based on 57 different feature types, followed by feature engineering and hyperparameter optimization for machine learning models, respectively. The selected feature subsets of ENCAP are primarily composed of physicochemical properties, with several features specifically related to hydrophobicity and amphiphilicity. Two publicly available datasets were used for performance evaluation. ENCAP yields an AUC (Area Under the ROC Curve) of 0.768 and an MCC (Matthew's Correlation Coefficient) of 0.522 on the first independent test set. On the second test set, it achieves an AUC of 0.960 and an MCC of 0.789. Performance evaluations show that ENCAP generates 4.8% and 13.5% improvements in MCC over the state-of-the-art methods on two popular TTCA datasets, respectively. For the third test dataset of 71 experimentally validated TTCAs from the literature, ENCAP yields prediction accuracy of 0.873, achieving improvements ranging from 12% to 25.7% compared to three state-of-the-art methods. In general, the prediction accuracy is higher for sequences of fewer hydrophobic residues, and more hydrophilic and charged residues. The source code of ENCAP is freely available at https://github.com/YnnJ456/ENCAP.

Photodynamic and Antibacterial Assessment of Gold Nanoparticles Mediated by Gold (III) Chloride Trihydrate and Sodium Citrate under Alkaline Conditions.

Sodium citrate (SC) is sensitive to violet light illumination (VLI) and acts as a weak reductant. Conversely, gold (III) chloride trihydrate (GC) often acts as an oxidant in a redox reaction. In this study, the influences of colored light on the production of gold nanoparticles (AuNPs) in a mixture of gold (III) ions and citrate via VLI and the antibacterial photodynamic inactivation (aPDI) of Escherichia coli (E. coli) are determined under alkaline conditions. The diameter of AuNPs is within the range of 3-15 nm, i.e., their mean diameter is 9 nm; when citrate is mixed with gold (III) ions under VLI, AuNPs are formed via an electron transfer process. Additionally, GC mixed with SC (GCSC) inhibits E. coli more effectively under VLI than it does under blue, green, or red light. GCSC and SC are shown to inhibit E. coli populations by 4.67 and 1.12 logs, respectively, via VLI at 10 W/m2 for 60 min under alkaline conditions. GCSC-treated E. coli has a more significant photolytic effect on anionic superoxide radical (O2•-) formation under VLI, as more O2•- is formed within E. coli if the GCSC-treated samples are subjected to VLI. The O2•- exhibits a greater effect in a solution of GCSC than that shown by SC alone under VLI treatment. Gold (III) ions in a GCSC system appear to act as an oxidant by facilitating the electron transfer from citrate under VLI and the formation of AuNPs and O2•- via GCSC photolysis under alkaline conditions. As such, the photolysis of GCSC under VLI is a useful process that can be applied to aPDI.

Composite bone graft of CaO-MgO-SiO2 glass-ceramics and CaSO4 ceramics for boosting bone formation rate.

This study develops a composite bone graft of CaO-MgO-SiO2 glass-ceramic and CaSO4 [abbreviated as (CMS)3-x(CS)x] via the sponge replication technique with weight fractions of x = 0, 1, 1.5, 2, and 3. The (CMS)1.5(CS)1.5 composite displays a superior degradability and, a suitable compressive strength of ∼3 MPa, and excellent cell proliferation and differentiation. The in vivo rat femur test in the hybrid-pore (CMS)1.5(CS)1.5 composite granules achieves a higher rate of bone formation, which is ∼2.7 times better than that of the commercial HAP/ß-TCP at 12 weeks. Improved expressions of osteocyte and mature osteocyte marker genes, namely (Spp1, Dmp1, and Fgf23), were observed in the (CMS)1.5(CS)1.5 group, indicating a faster differentiation into mature bone tissue. The ions release of (CMS)1.5(CS)1.5 through the ERK1/2 signaling pathway promotes osteogenic differentiation. The high bone generation rate can be attributed to faster active ions release and modified surface topography. This work highlights an excellent bone graft candidate for clinical applications in orthopedic surgery.

Biological Age, Chronological Age and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.

RATIONALE: Accelerated biological aging has been implicated in the development of interstitial lung disease (ILD) and other diseases of aging but remains poorly understood. OBJECTIVES: To identify plasma proteins that mediate the relationship between chronological age and survival association in patients with ILD. METHODS: Causal mediation analysis was performed to identify plasma proteins that mediated the chronological age-survival relationship in an idiopathic pulmonary fibrosis (IPF) discovery cohort. Proteins mediating this relationship after adjustment for false discovery were advanced for testing in an independent ILD validation cohort and explored in a chronic obstructive pulmonary disease (COPD) cohort. A proteomic-based measure of biological age was constructed and survival analysis performed assessing the impact of biological age and peripheral blood telomere length on the chronological age-survival relationship. RESULTS: Twenty-two proteins mediated the chronological age-survival relationship after adjustment for false discovery in the IPF discovery cohort (n=874), with nineteen remaining significant mediators of this relationship in the ILD validation cohort (n=983) and one mediating this relationship in the COPD cohort. Latent transforming growth factor beta binding protein 2 and ectodysplasin A2 receptor showed the strongest mediation across cohorts. A proteomic measure of biological age completely attenuated the chronological age-survival association and better discriminated survival than chronological age. Results were robust to adjustment for peripheral blood telomere length, which did not mediate the chronological age-survival relationship. CONCLUSIONS: Molecular measures of aging completely mediate the relationship between chronological age and survival, suggesting that chronological age has no direct effect on ILD survival.

Calibration algorithms for continuous glucose monitoring systems based on interstitial fluid sensing.

Continuous glucose monitoring (CGM) is of great importance to the treatment and prevention of diabetes. As a proven commercial technology, electrochemical glucose sensor based on interstitial fluid (ISF) sensing has high sensitivity and wide detection range. Therefore, it has good promotion prospects in noninvasive or minimally-invasive CGM system. However, since there are concentration differences and time lag between glucose in plasma and ISF, the accuracy of this type of sensors are still limited. Typical calibration algorithms rely on simple linear regression which do not account for the variability of the sensitivity of sensors. To enhance the accuracy and stability of CGM based on ISF, optimization of calibration algorithm for sensors is indispensable. While there have been considerable researches on improving calibration algorithms for CGM, they have still received less attention. This article reviews the problem of typical calibration and presents the outstanding calibration algorithms in recent years. Finally, combined with existing research and emerging sensing technologies, this paper makes an outlook on the future calibration algorithms for CGM sensors.

Improved prediction of anti-angiogenic peptides based on machine learning models and comprehensive features from peptide sequences.

Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting angiogenesis, are promising candidates in cancer treatment. We propose AAPL, a sequence-based predictor to identify AAPs with machine learning models of improved prediction accuracy. Each peptide sequence was transformed to a vector of 4335 numeric values according to 58 different feature types, followed by a heuristic algorithm for feature selection. Next, the hyperparameters of six machine learning models were optimized with respect to the feature subset. We considered two datasets, one with entire peptide sequences and the other with 15 amino acids from peptide N-termini. AAPL achieved Matthew's correlation coefficients of 0.671 and 0.756 for independent tests based on the two datasets, respectively, outperforming existing predictors by a range of 5.3% to 24.6%. Further analyses show that AAPL yields higher prediction accuracy for peptides with more hydrophobic residues, and fewer hydrophilic and charged residues. The source code of AAPL is available at https://github.com/yunzheng2002/Anti-angiogenic .

Molecular Endotypes of Idiopathic Pulmonary Fibrosis: A Latent Class Analysis of Two Multicenter Observational Cohorts.

Rationale: Idiopathic pulmonary fibrosis (IPF) causes irreversible fibrosis of the lung parenchyma. While antifibrotic therapy can slow IPF progression, treatment response is variable. There exists a critical need to develop a precision medicine approach to IPF. Objective: To identify and validate biologically driven molecular endotypes of IPF. Methods: Latent class analysis (LCA) was independently performed in prospectively recruited discovery (n=875) and validation (n=347) cohorts. Twenty-five plasma biomarkers associated with fibrogenesis served as class-defining variables. The association between molecular endotype and 4-year transplant-free survival was tested using multivariable Cox regression adjusted for baseline confounders. Endotype-dependent differential treatment response to future antifibrotic exposure was then assessed in a pooled cohort of patients naïve to antifibrotic therapy at time of biomarker measurement (n=555). Results: LCA independently identified two latent classes in both cohorts (p<0.0001). WAP four-disulfide core domain protein 2 (WFDC2) was the most important determinant of class membership across cohorts. Membership in Class 2 was characterized by higher biomarker concentrations and higher risk of death or transplantation (discovery: HR 2.02 [95% CI 1.64-2.48]; p<0.001; validation: HR 1.95 [1.34-2.82]; p<0.001). In pooled analysis, significant heterogeneity in treatment effect was observed between endotypes (pinteraction=0.030), with a favorable antifibrotic response in Class 2 (HR 0.64 [0.45-0.93]; p=0.018) but not in Class 1 (HR 1.19 [0.77-1.84]; p=0.422). Conclusions: In this multicohort study, we identified two novel molecular endotypes of IPF with divergent clinical outcomes and response to antifibrotics. Pending further validation, these endotypes could enable a precision medicine approach for future IPF clinical trials.

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed "cycling M2", which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Comparative Single Vesicle Analysis of Aqueous Humor Extracellular Vesicles before and after Radiation in Uveal Melanoma Eyes.

Small extracellular vesicles (sEVs) have been shown to promote tumorigenesis, treatment resistance, and metastasis in multiple cancer types; however, sEVs in the aqueous humor (AH) of uveal melanoma (UM) patients have never previously been profiled. In this study, we used single particle analysis to characterize sEV subpopulations in the AH of UM patients by quantifying their size, concentration, and phenotypes based on cell surface markers, specifically the tetraspanin co-expression patterns of CD9, CD63, and CD81. sEVs were analyzed from paired pre- and post-treatment (brachytherapy, a form of radiation) AH samples collected from 19 UM patients. In post-brachytherapy samples, two subpopulations, CD63/81+ and CD9/63/81+ sEVs, were significantly increased. These trends existed even when stratified by tumor location and GEP class 1 and class 2 (albeit not significant for GEP class 2). In this initial report of single vesicle profiling of sEVs in the AH of UM patients, we demonstrated that sEVs can be detected in the AH. We further identified two subpopulations that were increased post-brachytherapy, which may suggest radiation-induced release of these particles, potentially from tumor cells. Further study of the cargo carried by these sEV subpopulations may uncover important biomarkers and insights into tumorigenesis for UM.

The Effect of Age on Cerebral Vasospasm and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The association between patient age and cerebral arterial vasospasm (CVS) and delayed cerebral ischemia (DCI) risk following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. This study aims to assess the role of age on aSAH-related complications. METHODS: Single-center retrospective study comprising aSAH patients treated between January 2009 and March 2023. Age was analyzed as continuous and categorical variables (<60 yrs vs. ≥60 yrs and by decade). Outcomes of interest included radiographic CVS, DCI, cerebral infarction, in-hospital mortality, length-of-stay (LOS), ventriculoperitoneal shunt placement, and modified Rankin Scale (mRS) scores at discharge and 3-month follow-up. RESULTS: Nine hundred and twenty-five aSAH patients were included. Most (n = 598; 64.6%) were <60 yrs old (46 ± 9.1 yrs). CVS likelihood was lower in the older cohort (aOR = 0.56 [0.38-0.82]). Patients ≥60 yrs had higher mortality rates (aOR = 2.24 [1.12-4.47]) and worse mRS scores at discharge (aOR = 2.66 [1.91-3.72]) and 3-month follow-up (aOR = 2.19 [1.44-3.32]). Advanced age did not have a significant effect on DCI or cerebral infarction risk. Higher in-hospital mortality was documented with increasing age (P < 0.001). A significant interaction between CVS and age for the outcome of DCI was documented, with a stronger positive effect on poor outcomes (i.e., higher odds of DCI) among patients aged <60 years compared to those aged ≥60. CONCLUSIONS: There is an inverse relationship between patient age and CVS incidence following aSAH. Nonetheless, patients ≥60 yrs had comparable DCI rates, higher in-hospital mortality, and worse functional outcomes than their younger counterparts. Routine screening and reliance on radiographic CVS as primary marker for aSAH-related complications should be reconsidered, particularly in older patients.

Retinoblastoma with MYCN Amplification Diagnosed from Cell-Free DNA in the Aqueous Humor.

Introduction: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling. Methods: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data. Results: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression. Conclusions: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation. Importance: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.

Fully human chitinase-3 like-1 monoclonal antibody inhibits tumor growth, fibrosis, angiogenesis, and immune cell remodeling in lung, pancreatic, and colorectal cancers.

Considering the limited efficacy of current therapies in lung, colorectal, and pancreatic cancers, innovative combination treatments with diverse mechanisms of action are needed to improve patients' outcomes. Chitinase-3 like-1 protein (CHI3L1) emerges as a versatile factor with significant implications in various diseases, particularly cancers, fostering an immunosuppressive tumor microenvironment for cancer progression. Therefore, pre-clinical validation is imperative to fully realize its potential in cancer treatment. We developed phage display-derived fully human monoclonal CHI3L1 neutralizing antibodies (nAbs) and verified the nAbs-antigen binding affinity and specificity in lung, pancreatic and colorectal cancer cell lines. Tumor growth signals, proliferation and migration ability were all reduced by CHI3L1 nAbs in vitro. Orthotopic or subcutaneous tumor mice model and humanized mouse model were established for characterizing the anti-tumor properties of two CHI3L1 nAb leads. Importantly, CHI3L1 nAbs not only inhibited tumor growth but also mitigated fibrosis, angiogenesis, and restored immunostimulatory functions of immune cells in pancreatic, lung, and colorectal tumor mice models. Mechanistically, CHI3L1 nAbs directly suppressed the activation of pancreatic stellate cells and the transformation of macrophages into myofibroblasts, thereby attenuating fibrosis. These findings strongly support the therapeutic potential of CHI3L1 nAbs in overcoming clinical challenges, including the failure of gemcitabine in pancreatic cancer.

In Operando X-ray Spectroscopic and DFT Studies Revealing Improved H2 Evolution by the Synergistic Ni-Co Electron Effect in the Alkaline Condition.

The different electrolyte conditions, e.g., pH value, for driving efficient HER and OER are one of the major issues hindering the aim for electrocatalytic water splitting in a high efficiency. In this regard, seeking durable and active HER electrocatalysts to align the alkaline conditions of the OER is a promising solution. However, the success in this strategy will depend on a fundamental understanding about the HER mechanism at the atomic scale. In this work, we have provided thorough understanding for the electrochemical HER mechanisms in KOH over Ni- and Co-based hollow pyrite microspheres by in operando X-ray spectroscopies and DFT calculations, including NiS2, CoS2, and Ni0.5Co0.5S2. We discovered that the Ni sites in hollow NiS2 microspheres were very stable and inert, while the Co sites in hollow CoS2 microspheres underwent reduction and generated Co metallic crystal domains under HER. The generation of Co metallic sites would further deactivate H2 evolution due to the large hydrogen desorption free energy (-1.73 eV). In contrast, the neighboring Ni and Co sites in hollow Ni0.5Co0.5S2 microspheres exhibited the electronic interaction to elevate the reactivity of Ni and facilitate the stability of Co without structure or surface degradation. The energy barrier in H2O adsorption/dissociation was only 0.73 eV, followed by 0.06 eV for hydrogen desorption over the Ni0.5Co0.5S2 surface, revealing Ni0.5Co0.5S2 as a HER electrocatalyst with higher durability and activity than NiS2 and CoS2 in the alkaline medium due to the synergy of neighboring Ni and Co sites. We believe that the findings in our work offer a guidance toward future catalyst design.

Combining anchoring with financial incentives to increase physical activity: a randomized controlled trial among college students.

The purpose of this study was to: (1) compare the relative efficacy of different combinations of three behavioral intervention strategies (i.e., personalized reminders, financial incentives, and anchoring) for establishing physical activity habits using an mHealth app and (2) to examine the effects of these different combined interventions on intrinsic motivation for physical activity and daily walking habit strength. A four-arm randomized controlled trial was conducted in a sample of college students (N = 161) who had a self-reported personal wellness goal of increasing their physical activity. Receiving cue-contingent financial incentives (i.e., incentives conditional on performing physical activity within ± one hour of a prespecified physical activity cue) combined with anchoring resulted in the highest daily step counts and greatest odds of temporally consistent walking during both the four-week intervention and the full eight-week study period. Cue-contingent financial incentives were also more successful at increasing physical activity and maintaining these effects post-intervention than traditional non-cue-contingent incentives. There were no differences in intrinsic motivation or habit strength between study groups at any time point. Financial incentives, particularly cue-contingent incentives, can be effectively used to support the anchoring intervention strategy for establishing physical activity habits. Moreover, mHealth apps are a feasible method for delivering the combined intervention technique of financial incentives with anchoring.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). METHODS: The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. RESULTS: A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. CONCLUSION: Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.