P2y12 inhibitor monotherapy after 1–3 months dual antiplatelet therapy in patients with coronary artery disease and chronic kidney disease undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

IntroductionIn patients with coronary artery disease (CAD) and chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI), whether short-term dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitors confers benefits compared with standard DAPT remains unclear. This study aimed to assess the efficacy and safety of 1–3 months of DAPT followed by P2Y12 monotherapy in patients with CAD and CKD undergoing PCI.MethodsPubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials (RCTs) comparing the P2Y12 inhibitor monotherapy after a 1–3 months DAPT vs. DAPT in patients with CAD and CKD after PCI. The primary outcome was the incidence of major adverse cardiovascular events (MACEs), defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, target-vessel revascularization, and stroke. The safety outcome was the major bleeding events, defined as a composite of TIMI major bleeding or Bleeding Academic Research and Consortium (BARC) type 2, 3, or 5 bleeding. The pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated with a fixed- or random-effects model depending on the heterogeneity among studies.ResultsFour RCTs including 20,468 patients (2,833 patients with CKD and 17,635 without CKD) comparing P2Y12 inhibitor monotherapy with DAPT were included in our meta-analysis. Patients with CAD and CKD had higher risk of ischemic and bleeding events. P2Y12 inhibitor monotherapy after 1–3 months of DAPT significantly reduced the risk of major bleeding compared to DAPT in CKD patients (RR: 0.69, 95% CI: 0.51–0.95, P = 0.02) and non-CKD patients (RR: 0.66, 95% CI: 0.49–0.89, P = 0.01). No significant difference regarding MACEs between P2Y12 inhibitor monotherapy and DAPT was found in CKD patients (RR: 0.88, 95% CI: 0.59–1.31, P = 0.53) and non-CKD (RR: 0.91, 95% CI: 0.79–1.04, P = 0.17).ConclusionP2Y12 inhibitor monotherapy after 1–3 months of DAPT was an effective strategy for lowering major bleeding complications without increasing the risk of cardiovascular events in patients with CAD and CKD undergoing PCI as compared with DAPTSystematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42022355228

SciBench: Evaluating College-Level Scientific Problem-Solving Abilities of Large Language Models

Recent advances in large language models (LLMs) have demonstrated notable progress on many mathematical benchmarks. However, most of these benchmarks only feature problems grounded in junior and senior high school subjects, contain only multiple-choice questions, and are confined to a limited scope of elementary arithmetic operations. To address these issues, this paper introduces an expansive benchmark suite SciBench that aims to systematically examine the reasoning capabilities required for complex scientific problem solving. SciBench contains two carefully curated datasets: an open set featuring a range of collegiate-level scientific problems drawn from mathematics, chemistry, and physics textbooks, and a closed set comprising problems from undergraduate-level exams in computer science and mathematics. Based on the two datasets, we conduct an in-depth benchmark study of two representative LLMs with various prompting strategies. The results reveal that current LLMs fall short of delivering satisfactory performance, with an overall score of merely 35.80%. Furthermore, through a detailed user study, we categorize the errors made by LLMs into ten problem-solving abilities. Our analysis indicates that no single prompting strategy significantly outperforms others and some strategies that demonstrate improvements in certain problem-solving skills result in declines in other skills. We envision that SciBench will catalyze further developments in the reasoning abilities of LLMs, thereby ultimately contributing to scientific research and discovery.Comment: Work in progress, 18 page

Simulation and Validation of Droplet Generation Process for Revealing Three Design Constraints in Electrohydrodynamic Jet Printing

Droplet generation process can directly affect process regulation and output performance of electrohydrodynamic jet (E-jet) printing in fabricating micro-to-nano scale functional structures. This paper proposes a numerical simulation model for whole process of droplet generation of E-jet printing based on the Taylor-Melcher leaky-dielectric model. The whole process of droplet generation is successfully simulated in one whole cycle, including Taylor cone generation, jet onset, jet break, and jet retraction. The feasibility and accuracy of the numerical simulation model is validated by a 30G stainless nozzle with inner diameter ~160 μm by E-jet printing experiments. Comparing numerical simulations and experimental results, period, velocity magnitude, four steps in an injection cycle, and shape of jet in each step are in good agreement. Further simulations are performed to reveal three design constraints against applied voltage, flow rate, and nozzle diameter, respectively. The established cone-jet numerical simulation model paves the way to investigate influences of process parameters and guide design of printheads for E-jet printing system with high performance in the future

Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease

Objective: Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated. Methods: Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined. Results: The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation. Conclusions: Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD

Efficacy and safety of weekly nab-paclitaxel plus gemcitabine in Chinese patients with metastatic adenocarcinoma of the pancreas: a phase II study

Abstract Background This phase II bridging study assessed the safety and efficacy of nab-paclitaxel/gemcitabine (Metastatic Pancreatic Adenocarcinoma Clinical Trial [MPACT] regimen) in Chinese patients with metastatic pancreatic cancer (MPC). Methods This 3-part sequential study evaluated nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. Part 1 evaluated safety. Part 2 evaluated efficacy using Simon’s optimal 2-stage design: if >2 responses were observed in Stage 1 (n = 28), 54 additional patients would be enrolled in Stage 2. If >9 responses were observed, the study was complete. Otherwise, nab-paclitaxel/gemcitabine would be compared with gemcitabine alone in Part 3. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Results Eighty-three patients were treated. The prespecified primary endpoint was met: the independently assessed ORR in Stages 1 + 2 was 35% (95% CI, 24.8–46.2); therefore, Part 3 was not initiated. The median DOR was 8.9 months (95% CI, 6.01–8.94). The median OS and progression-free survival were 9.2 (95% CI, 7.6–11.1) and 5.5 (95% CI, 5.29–7.16) months, respectively. The 12-month OS rate was 30%. In an updated analysis, the median OS was 9.3 months and the 12-month OS rate was 32%. Longer OS was observed in patients with baseline neutrophil-to-lymphocyte ratio ≤ 5 vs > 5. The most common grade ≥ 3 adverse events were leukopenia (35%), neutropenia (34%), anemia (15%), thrombocytopenia (10%), and fatigue (13%). Grade 3 peripheral neuropathy occurred in 7% of patients (no grade 4 reported). Conclusions The MPACT regimen of nab-paclitaxel/gemcitabine is efficacious in Chinese patients with MPC. No new safety signals were observed. Trial registration NCT02135822 , May 8, 2014

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition)

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases