Picosecond alexandrite laser treatment of nevus of Ota in children.

BACKGROUND: The picosecond alexandrite laser has been safely and effectively used to treat the nevus of Ota in adults. However, limited data are available for children. OBJECTIVE: To investigate the efficacy, safety, and correlative influencing factors of a 755nm picosecond alexandrite laser in the treatment of nevus of Ota in children. METHODS: We retrospectively analyzed Chinese children with nevus of Ota who received a 755nm picosecond alexandrite laser treatment in a tertiary dermatological hospital. RESULT: A total of 305 pediatric patients received an average of two treatments achieving an average of 79% pigment clearance. After the first treatment, 22 patients achieved complete clearance (95%-100%), and 72 patients achieved excellent response (75%-94%), with an average initial efficacy of 63% lesion clearance. Treatment at an early age achieved better initial efficacy (0- to 12-month group >1- to 6-year group, 6- to 12-year group). And 0- to 12-month group achieved better final efficacy. More treatment sessions also increased the final efficacy. Both initial efficacy and final efficacy were better when treating a darker lesion. The incidence of complications was 12.1%, with 10.8% being post-inflammatory hyperpigmentation and 1.3% being hypopigmentation. The rate of recurrence was 6.6%. LIMITATION: Retrospective study. CONCLUSION: A 755nm picosecond alexandrite laser is safe and effective in treating nevus of Ota in children. Younger to initiate treatment, darker lesions, and more treatments are positively associated with better pigmentation clearance.

Investigation of folate-modified EGCG-loaded thermosensitive nanospheres inducing immunogenic cell death and damage-associated molecular patterns in hepatocellular carcinoma.

BACKGROUND: The systemic treatment of advanced hepatocellular carcinoma is currently facing a bottleneck. EGCG, the primary active compound in green tea, exhibits anti-tumor effects through various pathways. However, there is a lack of study on EGCG-induced immunogenic cell death (ICD) in hepatocellular carcinoma. METHODS: In a previous study, we successfully synthesized folate-modified thermosensitive nano-materials, encapsulated EGCG within nanoparticles using a hydration method, and established the EGCG nano-drug delivery system. The viability of HepG2 cells post-EGCG treatment was assessed via the MTT and EdU assays. Cell migration and invasion were evaluated through wound healing experiments, Transwell assays, and Annexin V-FITC/PI assay for apoptosis detection. Additionally, the expression levels of damage-associated molecular patterns (DAMPs) were determined using immunofluorescence, ATP measurement, RT-qPCR, and Western Blot. RESULTS: The drug sensitivity test revealed an IC50 value of 96.94 µg/mL for EGCG in HepG2 cells after 48 h. EGCG at a low concentration (50 µg/mL) significantly impeded the migration and invasion of HepG2 cells, showing a clear dose-dependent response. Moreover, medium to high EGCG concentrations induced cell apoptosis in a dose-dependent manner and upregulated DAMPs expression. Immunofluorescence analysis demonstrated a notable increase in CRT expression following low-concentration EGCG treatment. As EGCG concentration increased, cell viability decreased, leading to CRT exposure on the cell membrane. EGCG also notably elevated ATP levels. RT-qPCR and Western Blot analyses indicated elevated expression levels of HGMB1, HSP70, and HSP90 following EGCG intervention. CONCLUSION: EGCG not only hinders the proliferation, migration, and invasion of hepatocellular carcinoma cells and induces apoptosis, but also holds significant clinical promise in the treatment of malignant tumors by promoting ICD and DAMPs secretion.

Could a low-dose definitive radiation therapy be the optimal treatment for choroidal hemangioma?

PURPOSE: To determine the efficacy of low-dose intensity-modulated radiation therapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) in the treatment of symptomatic choroidal hemangioma (CH). MATERIALS AND METHODS: Fifty-three consecutive patients with CH were retrospectively reviewed. All the patients underwent IMRT/VMAT as a unique treatment. Resolution of subretinal fluid (SRF), improvement of best-corrected visual acuity (BCVA), and reduction in tumor thickness were compared before and after radiotherapy. RESULTS: After definitive radiotherapy, 100 % of SRF and 76.7 % of exudative retinal detachment were resolved. 56.6 % of BCVA improvement in more than two lines was observed. The mean best-corrected visual acuity was 20/280 (range, 20/1200-20/40) at diagnosis and 20/100 (range, 20/1200-20/20) after treatment. The mean tumor thickness decreased significantly from 3.8 mm initially to 1.2 mm after treatment (p < 0.01). 66.0 % of patients were delivered with 21.6 Gy (range, 21.6-42 Gy), 84.9 % of fractional dose was 1.8 Gy (range, 1.8-2 Gy). No radiation-induced keratitis, retinopathy, or optic neuropathy were observed. Initial vision (p = 0.042), duration time of vision (p = 0.004), and tumor thickness (p = 0.049) were prognostic factors for vision recovery. CONCLUSION: Low-dose IMRT/VMAT could effectively induce involution of the CH, with reduction of subretinal fluid and relief of damage to the neurosensory retina, which is an effective treatment mode for CH.

Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children's Oncology Group Study.

Background: Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab. Methods: Patients ≥ 3 and < 22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54-59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy. Results: Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%), and 59.3% (±9.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P = .03), whereas H3.3 K27M mutations (P = .0045) and alterations in PIK3CA or PTEN (P = .025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n = 4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P = .002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P = .0012). Conclusions: Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.

Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

PURPOSE: To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). METHODS: A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50 min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. RESULTS: The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. CONCLUSION: The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

Design of target specific peptide inhibitors using generative deep learning and molecular dynamics simulations.

We introduce a computational approach for the design of target-specific peptides. Our method integrates a Gated Recurrent Unit-based Variational Autoencoder with Rosetta FlexPepDock for peptide sequence generation and binding affinity assessment. Subsequently, molecular dynamics simulations are employed to narrow down the selection of peptides for experimental assays. We apply this computational strategy to design peptide inhibitors that specifically target ß-catenin and NF-κB essential modulator. Among the twelve ß-catenin inhibitors, six exhibit improved binding affinity compared to the parent peptide. Notably, the best C-terminal peptide binds ß-catenin with an IC50 of 0.010 ± 0.06 µM, which is 15-fold better than the parent peptide. For NF-κB essential modulator, two of the four tested peptides display substantially enhanced binding compared to the parent peptide. Collectively, this study underscores the successful integration of deep learning and structure-based modeling and simulation for target specific peptide design.

Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007-2012).

BACKGROUND: Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet. METHODS: Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations. RESULTS: This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman's rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (ß = 1.979 ppb and ß = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The ß coefficient for serum Klotho was 0.002 ppb/pg/ml. CONCLUSIONS: Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors.

PURPOSE: The objectives of this study were to develop a population pharmacokinetic model of methotrexate (MTX) and its primary metabolite 7-hydroxymethotrexate (7OHMTX) in children with brain tumors, to identify the sources of pharmacokinetic variability, and to assess whether MTX and 7OHMTX systemic exposures were related to toxicity. METHODS: Patients received 2.5 or 5 g/m2 MTX as a 24-hour infusion and serial samples were analyzed for MTX and 7OHMTX by an LC-MS/MS method. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Demographics, laboratory values, and genetic polymorphisms were considered as potential covariates to explain the pharmacokinetic variability. Association between MTX and 7OHMTX systemic exposures and MTX-related toxicities were explored using random intercept logistic regression models. RESULTS: The population pharmacokinetics of MTX and 7OHMTX were adequately characterized using two-compartment models in 142 patients (median 1.91 y; age range 0.09 to 4.94 y) in 513 courses. The MTX and 7OHMTX population clearance values were 4.6 and 3.0 l/h/m2, respectively. Baseline body surface area and estimated glomerular filtration rate were significant covariates on both MTX and 7OHMTX plasma disposition. Pharmacogenetic genotypes were associated with MTX pharmacokinetic parameters but had only modest influence. No significant association was observed between MTX or 7OHMTX exposure and MTX-related toxicity. CONCLUSIONS: MTX and 7OHMTX plasma disposition were characterized for the first time in young children with brain tumors. No exposure-toxicity relationship was identified in this study, presumably due to aggressive clinical management which led to a low MTX-related toxicity rate.

The treatment efficacy of radiotherapy for optic nerve sheath meningioma.

OBJECTIVES: Optic nerve sheath meningioma (ONSM) is a rare benign tumour that accounts for approximately 2% of all orbital tumours. Radiotherapy has gradually become an important treatment for ONSM because of its good effect in preserving or improving vision. We aimed to explore the effect of radiotherapy on tumour control and vision preservation/improvement in patients with ONSM. METHODS: Forty-three patients with primary ONSM treated in our institution from 2015 to 2021 were enrolled. The irradiation dose was from 50.4 to 54 Gy with 28-30 fractions. We evaluated the tumour volume on MRI or CT, and visual acuity before and after the radiotherapy. RESULTS: Thirty-four patients (79%) experienced a vision decrease at diagnosis. The mean duration of follow-up was 54.1 months (ranges: 18-93, median: 56). Among 25 patients who had tumour evaluation using MRI, 16 patients (37.2%) showed stable tumours, 7 patients (16.3%) had tumour shrinkage, but 2 patients (4.7%) experienced tumour progression. Among the 39 patients performing vision acuity evaluation, 16 patients (37.2%) had vision improvement or recovery. 16 of the 23 patients without vision improvement demonstrated severe visual loss at diagnosis. Two patients had evidence of tumour progression during the follow-up. Additionally, 4 (10.2%) patients had dry eyes, 7 (17.9%) patients experienced watery eyes, and 3 (7.7%) patients had eye swelling. Patients with vision loss for more than 12 months had a lower possibility of vision recovery than those with vision loss for less than 12 months. CONCLUSIONS: Radiotherapy such as IMRT, VMAT, and 3D-CRT plays an important role in the treatment of ONSM. The probability of vision recovery is lower in patients with severe vision loss at diagnosis or the duration of vision loss is more than 12 months.

RAD54B inhibits vascular endothelial senescence via suppression of CHK1/p53/p21 pathway.

RAD54B belongs to the SNF2/SWI2 superfamily, participating in homologous recombination repair. DNA damage is the central driver of aging, but there is no direct evidence of an association between RAD54B and vascular aging. The present study sought to investigate the role and mechanisms of RAD54B in endothelial senescence. In senescent animal models, including spontaneously hypertensive rats, normal aging mice, and D-gal-induced senescent mice, and senescent cell models induced by H2O2, D-gal, and culture, RAD54B was remarkably downregulated. Knockdown of RAD54B increased the expression of p53 and p21, increased the ratio of SA-ß-gal-positive cells, and decreased the proportion of EdU-positive cells. Conversely, overexpression of RAD54B reversed the senescent phenotypes stimulated by H2O2 and delayed replicative endothelial senescence. Mechanistically, silencing RAD54B compensatorily increased the expression of RAD51/XRCC4, which remained unchanged in H2O2-induced senescence. RAD54B lacking the SNF2 domain could still reverse the increasing expression of p53/p21 induced by H2O2. RAD54B reduced γH2A.X expression and inhibited the expression and phosphorylation of CHK1. In conclusion, RAD54B exerts a direct protective effect against DNA damage through enhancing homologous recombination repair in endothelial senescence, resulting in inhibition of the downstream CHK1/p53/p21 pathway, suggesting that RAD54B may be a potential therapeutic target for vascular aging-associated diseases.

The role of robotic surgery in neurological cases: A systematic review on brain and spine applications.

The application of robotic surgery technologies in neurological surgeries resulted in some advantages compared to traditional surgeries, including higher accuracy and dexterity enhancement. Its success in various surgical fields, especially in urology, cardiology, and gynecology surgeries was reported in previous studies, and similar advantages in neurological surgeries are expected. Surgeries in the central nervous system with the pathology of millimeters through small working channels around vital tissue need especially high precision. Applying robotic surgery is therefore an interesting dilemma for these situations. This article reviews various studies published on the application of brain and spine robotic surgery and discusses the current application of robotic technology in neurological cases.

Narrow-Band Intense Pulsed Light as Treatment for Erythematotelangiectatic Rosacea: A Retrospective Study.

BACKGROUND: Erythematotelangiectatic rosacea can be successfully treated using various laser and light-based devices. However, the use of narrow-band intense pulsed light for the treatment of erythematotelangiectatic rosacea has not been investigated in detail. This retrospective study aimed to analyze the clinical efficacy of narrow-band intense pulsed light (500-600 nm) for the treatment of erythematotelangiectatic rosacea among Chinese individuals.  Methods: Patients with erythematotelangiectatic rosacea who had completed 3 sessions of treatment with narrow-band intense pulsed light and follow-up from July 2016 to December 2018 were retrospectively evaluated. Clinical improvement was assessed by 2 blinded dermatologists based on photographs obtained at each follow-up visit using the clinician erythema assessment scale and 5-grade scale. RESULTS: Forty-five patients with erythematotelangiectatic rosacea treated with narrow-band intense pulsed light were included in this study. The effectiveness and excellent rates after 3 treatment sessions were 68.9% and 35.6%, respectively. An average of 2 treatment sessions was required among patients who achieved good or excellent clearance of erythema and telangiectasia. Except for transient erythema and edema, no severe adverse effects were observed. CONCLUSIONS: Narrow-band intense pulsed light is a safe and effective treatment for erythematotelangiectatic rosacea. Even with a small number of treatment sessions, narrow-band intense pulsed light can deliver a significant therapeutic effect, which may be applicable in clinical practice. J Drugs Dermatol. 2023;22(11):1095-1098     doi:10.36849/JDD.4920.

CDK5 promotes apoptosis and attenuates chemoresistance in gastric cancer via E2F1 signaling.

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

Treatment of nasal squamous cell carcinoma with combination of surgery and photodynamic therapy.

Cutaneous squamous cell carcinoma (cSCC) is a common malignant skin tumor. Some invasive cSCC can cause severe cosmetic damage; therefore, comprehensive measures should be taken. Here, we present a case of a 48-year-old male patient with invasive cSCC on the nose. The lesion recurred twice after excision in the other hospital. After admission, the patient underwent surgical excision; however, the tumor remained because of its deep infiltration, and we left the wound exposed without repair. During the period of open-wound, the patient received 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) to completely clear the residual tumors, and multipoint biopsies were performed to monitor the tumor remission process. We reconstructed the defect by using bilateral flaps after complete remission. The tumor did not recur in 63 months of follow-up after reconstruction. Open-wound treatment should be considered for tumors that occur at high-risk sites such as the nose. Surgery combined with PDT may be an efficient method for treating cSCC.

Lnc-PKNOX1-1 inhibits tumor progression in cutaneous malignant melanoma by regulating NF-κB/IL-8 axis.

Cutaneous malignant melanoma is one of the most lethal cutaneous malignancies. Accumulating evidence has demonstrated the potential influence of long non-coding RNAs (lncRNAs) in biological behaviors of melanoma. Herein, we reported a novel lncRNA, lnc-PKNOX1-1 and systematically studied its functions and possible molecular mechanisms in melanoma. Reverse transcription-quantitative PCR assay showed that lnc-PKNOX1-1 was significantly decreased in melanoma cells and tissues. Low lnc-PKNOX1-1 expression was significantly correlated with invasive pathological type and Breslow thickness of melanoma. In vitro and in vivo experiments showed lnc-PKNOX1-1 dramatically inhibited melanoma cell proliferation, migration and invasion. Mechanically, protein microarray analysis suggested that interleukin-8 (IL-8) was negatively regulated by lnc-PKNOX1-1 in melanoma, which was confirmed by western blot and ELISA. Western blot analysis also showed that lnc-PKNOX1-1 could promote p65 phosphorylation at Ser536 in melanoma. Subsequent rescue assays proved IL-8 overexpression could partly reverse the tumor-suppressing function of lnc-PKNOX1-1 overexpression in melanoma cells, indicating that lnc-PKNOX1-1 suppressed the development of melanoma by regulating IL-8. Taken together, our study demonstrated the tumor-suppressing ability of lnc-PKNOX1-1 in melanoma, suggesting its potential as a novel diagnostic biomarker and therapeutic target for melanoma.

Opportunities and challenges for ribosome-inactivating proteins in traditional Chinese medicine plants.

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

Vitamin D and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

BACKGROUND: A prospective study of multiple small samples found that idiopathic pulmonary fibrosis (IPF) is often accompanied by a deficiency in Vitamin D levels. However, the causal relationship between the two remains to be determined. Therefore, our study aims to investigate the causal effect of serum 1,25-hydroxyvitamin D (25(OH)D) on the risk of IPF through a two-sample Mendelian randomization (MR) analysis. METHODS: Through data analysis from two European ancestry-based genome-wide association studies (GWAS), including 401,460 individuals for 25(OH)D levels and 1028 individuals for IPF, we primarily employed inverse-variance weighted (IVW) to assess the causal effect of 25(OH)D levels on IPF risk. MR-Egger regression test was used to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis was conducted to examine the robustness of the results. RESULTS: 158 SNPs related to serum 25(OH)D were used as instrumental variables (IVs). The MR analyses revealed no evidence supporting a causal association between the level of circulating 25(OH)D and the risk of IPF. The IVW method [OR 0.891, 95%CI (0.523-1.518), P = 0.670]; There was no significant level of heterogeneity, pleiotropy and bias in IVs. Cochran's Q test for heterogeneity (MR Egger P = 0.081; IVW P = 0.089); MR-Egger regression for pleiotropy (P = 0.774). CONCLUSIONS: This MR Study suggests that genetically predicted circulating vitamin D concentrations in the general population are not causally related to IPF.

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study.

The phase III GALLIUM trial assessed the safety and efficacy of obinutuzumab-based versus rituximab-based immunochemotherapy in patients with previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL). At the primary analysis, the trial met its primary end point, demonstrating improvement in investigator-assessed progression-free survival (PFS) with obinutuzumab-based versus rituximab-based immunochemotherapy in patients with FL. We report the results of the final analysis in the FL population, with an additional exploratory analysis in the MZL subgroup. Overall, 1202 patients with FL were randomized 1:1 to obinutuzumab- or rituximab-based immunochemotherapy followed by maintenance with the same antibody for up to 2 years. After a median 7.9 (range, 0.0-9.8) years of follow-up, PFS remained improved with obinutuzumab- versus rituximab-based immunochemotherapy, with 7-year PFS rates of 63.4% versus 55.7% (P = 0.006). Time-to-next antilymphoma treatment was also improved (74.1% versus 65.4% of patients had not started their next antilymphoma treatment at 7 y; P = 0.001). Overall survival was similar between the arms (88.5% versus 87.2%; P = 0.36). Irrespective of the treatment received, PFS and OS were higher in patients with a complete molecular response (CMR) versus those with no CMR (P < 0.001). Serious adverse events were reported in 48.9% and 43.4% of patients in the obinutuzumab and rituximab arms, respectively; there was no difference in the rate of fatal adverse events (4.4% and 4.5%, respectively). No new safety signals were reported. These data demonstrate the long-term benefit of obinutuzumab-based immunochemotherapy and confirm its role as a standard-of-care for the first-line treatment of advanced-stage FL, taking into account patient characteristics and safety considerations.

Comparison of the efficacy and safety of a 730 nm picosecond titanium sapphire laser and a 755 nm picosecond alexandrite laser for the treatment of freckles in Asian patients: A two-center randomized, split-face, controlled trial.

OBJECTIVE: The 730 nm picosecond titanium sapphire laser is a novel laser that shows promising results in treating freckles. This study aimed to further investigate the efficacy and safety of the 730 nm picosecond titanium sapphire laser for treating freckles in Asian patients compared with those of the 755 nm picosecond alexandrite laser. METHODS: Each face of 86 participants was split into two parts and randomly assigned either one session of 730 or 755 nm picosecond-laser treatment each. Efficacy and safety were determined based on blinded visual evaluations and self-reports at each follow-up visit. RESULTS: The treatment outcomes of the 730 nm picosecond laser for the treatment of freckles were comparable to those of the 755 nm picosecond laser, with 68.99 ± 7.42% and 69.27 ± 7.75% clearance, respectively (p > 0.05). Participants achieved similar Global Aesthetic Improvement Scale scores (4.04 ± 0.31 vs. 4.02 ± 0.30, respectively [p > 0.05]). Additionally, the 730 nm picosecond laser was perceived to be less painful than the 755 nm picosecond laser (4.69 ± 1.63 vs. 5.65 ± 1.80 nm, p < 0.0001). CONCLUSION: The 730 nm picosecond laser is safe and effective for the treatment of freckles in Asian patients. Besides, the 730 nm picosecond laser is less painful than the 755 nm picosecond laser.

Intimately tracking NO2 pollution over the New York City - Long Island Sound land-water continuum: An integration of shipboard, airborne, satellite observations, and models.

Nitrogen dioxide (NO2) pollution remains a serious global problem, particularly near highly populated urbanized coasts that face increasing challenges with climate change. Yet, the combined impact of urban emissions, pollution transport, and complex meteorology on the spatiotemporal dynamics of NO2 along heterogeneous urban coastlines remains poorly characterized. Here, we integrated measurements from different platforms - boats, ground-based networks, aircraft, and satellites - to characterize total column NO2 (TCNO2) dynamics across the land-water continuum in the New York metropolitan area, the most populous area in the United States that often experiences the highest national NO2 levels. Measurements were conducted during the 2018 Long Island Sound Tropospheric Ozone Study (LISTOS), with a main goal to extend surface measurements beyond the coastline - where ground-based air-quality monitoring networks abruptly stop - and over the aquatic environment where peaks in air pollution often occur. Satellite TCNO2 from TROPOMI correlated strongly with Pandora surface measurements (r = 0.87, N = 100) both over land and water. Yet, TROPOMI overall underestimated TCNO2 (MPD = -12%) and missed peaks in NO2 pollution caused by rush hour emissions or pollution accumulation during sea breezes. Aircraft retrievals were in excellent agreement with Pandora (r = 0.95, MPD = -0.3%, N = 108). Stronger agreement was found between TROPOMI, aircraft, and Pandora over land, while over water satellite, and to a lesser extent aircraft, retrievals underestimated TCNO2 particularly in the highly dynamic New York Harbor environment. Combined with model simulations, our shipborne measurements uniquely captured rapid transitions and fine-scale features in NO2 behavior across the New York City - Long Island Sound land-water continuum, driven by the complex interplay of human activity, chemistry, and local scale meteorology. These novel datasets provide critical information for improving satellite retrievals, enhancing air quality models, and informing management decisions, with important implications for the health of diverse communities and vulnerable ecosystems along this complex urban coastline.