Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Adaptive spline surface fitting with arbitrary topological control mesh.

Reconstructing a spline surface from a given arbitrary topological triangle mesh is a fundamental and challenging problem in computer-aided design and engineering. This paper introduces a novel surface fitting method utilizing G-NURBS capable of handling control meshes with arbitrary topologies. This method employs adaptive control point adjustment, guided by the geometric attributes of the input model, ensuring precise representation of sharp features such as edges and corners. Two primary strategies are employed: a parameter correspondence approach designed for sharp features and a control mesh iterative refinement technique that incorporates geometrical feature information. The proposed method has been tested and evaluated on various CAD models to demonstrate its effectiveness. This method can achieve higher fitting accuracy while faithfully preserving the geometrical features with fewer control points.

Peripheral arterial rather than venous blood is a better source of circulating tumor cells in early lung cancer.

BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in the early diagnosis and prognosis of lung cancer. Identification of a more suitable sample source could be a breakthrough towards enhancing CTC detectability in early-stage lung cancer. We investigated the differences in detectable CTCs between peripheral arterial and venous blood in early- and mid-stage lung cancer patients undergoing surgery and analyzed the association between clinicopathological factors and detectable CTCs in peripheral arterial and venous blood. METHODS: Peripheral arterial and venous blood was collected in 5-mL samples from 56 patients with surgically resected and pathologically clear at early- or mid-stage lung cancer. Blood specimens were enriched for CTCs based on isolation by size of epithelial tumor cells. The CTCs were identified using Swiss Giemsa staining and immunohistochemistry for CD45/CD31. RESULTS: In stage I lung cancer, CTC-positive rate was significantly higher in peripheral arterial than in venous blood (45.45% vs. 17.39%). There was no significant difference in the number of detectable CTCs between peripheral arterial and venous blood. A low degree of differentiation was associated with a high positive rate of CTCs in peripheral venous blood. The number of circulating tumor microemboli was significantly higher in patients with tumor size >3 cm compared with ≤3 cm. CONCLUSION: CTC levels in peripheral arterial and venous blood differed little in lung cancer patients.Compared to peripheral venous blood, peripheral arterial blood had a higher CTC positivity rate in early-stage lung cancer.This study was favorable for early detection and monitoring of lung cancer.

Patching Non-Uniform Extraordinary Points.

Smooth surfaces from an arbitrary topological control grid have been widely studied, which are mostly generalized from splines with uniform knot intervals. These methods fail to work well on extraordinary points (EPs) whose edges have varying knot intervals. This paper presents a patching solution for arbitrary topological 2-manifold control grid with non-uniform knots that defines one bi-cubic Bézier patch per control grid face except those faces with EPs. Experimental results demonstrate that the new solution can improve the surface quality for non-uniform parameterization. Applications in surface reconstruction, arbitrary sharp features on the complex surface and tool path planning for the new surface representation are also provided in the paper.

A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

A framework from point clouds to workpieces.

Combining computer-aided design and computer numerical control (CNC) with global technical connections have become interesting topics in the manufacturing industry. A framework was implemented that includes point clouds to workpieces and consists of a mesh generation from geometric data, optimal surface segmentation for CNC, and tool path planning with a certified scallop height. The latest methods were introduced into the mesh generation with implicit geometric regularization and total generalized variation. Once the mesh model was obtained, a fast and robust optimal surface segmentation method is provided by establishing a weighted graph and searching for the minimum spanning tree of the graph for extraordinary points. This method is easy to implement, and the number of segmented patches can be controlled while preserving the sharp features of the workpiece. Finally, a contour parallel tool-path with a confined scallop height is generated on each patch based on B-spline fitting. Experimental results show that the proposed framework is effective and robust.

Comparison of short-term outcomes between laparoscopic-assisted and open complete mesocolic excision (CME) for the treatment of transverse colon cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Although laparoscopic-assisted complete mesocolic excision (LCME) is a superior treatment, there are few studies available on it owe to the low incidence and technical difficulty of LCME in transverse colon cancer. METHODS: The clinical data of 78 patients with transverse colon cancer who were treated by LCME and open complete mesocolic excision (OCME) were retrospectively analyzed. A total of 39 cases had been treated by LCME, compared with 39 cases treated by OCME. The patient characteristics and short-term outcomes including operation time, intra-operative blood loss, length of incision, time to first flatus, first postoperative ambulation, postoperative hospitalization time, number of harvested lymph nodes, length of resected specimen and incidence of complications were evaluated. RESULTS: There was no case converted to OCME in LCME group. LCME had significantly shorter length of incision, shorter operation time, less intra-operative blood loss, shorter postoperative hospitalization time (P<0.05). The length of resected specimen and the numbers of harvested lymph nodes were (26.5±5.4 cm) and (16.2±3.1) in LCME group, and (24.8±4.9 cm) and (15.1±3.5) in OCME group, with no differences between two groups. The incidence of wound infection was lower while the incidence of lymphatic leakage, anastomotic leakage, urinary tract infection and wound dehiscence had no significant differences between two groups. None of patients in these two groups developed urinary retention, anastomotic bleeding and postoperative intestinal obstruction. CONCLUSIONS: Our findings suggested that LCME is a safe, feasible and effective treatment method for the treatment of transverse colon cancer due to it can provide superior short-term outcomes including less intra-operative blood loss, faster recovery and lower incidence of wound infection.

[Effects of galectin-3 on proliferation and apoptosis of hepatic stellate cells].

OBJECTIVE: To observe the effects of galectin-3 on proliferation and apoptosis of hepatic stellate cells. METHODS: RT-PCR and Western blot were used to detect the expression of galectin-3 in hepatic stellate cells. Short hairpin DNA targeting galectin-3 of rat was was ligated into the recombinant vector pGCsilencer U6/Neo/GFP/shRNA plasmid. Then the plasmid was transfected into rat hepatic stellate cells. RT-PCR and Western blot were used to detect the interfering efficiency. Cell proliferation level was observed by CCK8 method at 24, 48 and 72 hours after transfection. Cell apoptosis was measured by Annexin V/PI-labeled flow cytometric analysis. RESULTS: Expression of galectin-3 in HSC was verified by both RT-PCR and Western blot. The recombinant vector was successfully constructed and verified, and was transfected into rat hepatic stellate cells. Western Blot and RT-PCR results demonstrated that the expression level of Galectin-3 was significantly down-regulated in galectin-3 shRNA transfected cells compared to control vector transferred cells. CCK8 assay indicated that proliferation of Galectin-3 knockdown cells was lower than that of control cells 48 and 72 hours post-transfection. Apoptotic cells in shRNA-interfering group were higher than those in control group both in early stage and advanced stage. CONCLUSION: Hepatic stellate cells can express galectin-3. Inhibition of galectin-3 using RNAi technique can suppress proliferation and induce apoptosis in HSC.