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Background: Coffee and tea consumption account for most caffeine intake and 2-3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem., Objectives: To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake., Methodology: We conducted PubMed and Embase searches using the terms "caffeine", "reward", "gene", "polymorphism", "addiction", "dependence" and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included., Results: A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2-5% effect size difference in number of cups of caffeinated drink for each allele per day., Conclusion: Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine., (© 2024. The Author(s).)

In this work, a water droplet impacting superhydrophobic flexible cantilever beams is systematically studied via experimental methods, aimed at recognizing the significance of the system dynamics that arises from the interplay between substrate oscillation and droplet impact. Influences of the substrate stiffness and the impact Weber number on the substrate oscillation and droplet impact dynamic are the focus particularly. For substrate oscillations, the beam deflection increases with the Weber number but decreases with the beam stiffness, while the oscillation period of the beam is not affected by the impact dynamic. For the droplet impact dynamic, the spreading dynamic is independent of beam oscillation, while the retraction dynamic is closely related to the surface elasticity. The effect of the cantilever beams on the droplet (i.e., promoting or inhibiting the rebound behavior) is dependent on the coupling movement of the water drop and the cantilever beam, which is varied by changing the stiffness of the cantilever beam. The findings of this work will provide a theoretical reference for the application of flexible substrates in the fields of anti-icing and self-cleaning.

Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality. Liver resection (LR) is a curative treatment for early-stage HCC, but the prognosis of HCC patients after LR is unsatisfactory because of tumor recurrence. Prognostic prediction models with great performance are urgently needed. The present study aimed to establish a novel prognostic nomogram to predict tumor recurrence in HCC patients after LR., Methods: We retrospectively analyzed 726 HCC patients who underwent LR between October 2011 and December 2016. Patients were randomly divided into the training cohort (n = 508) and the testing cohort (n = 218). The protein expression of 14 biomarkers in tumor tissues was assessed by immunohistochemistry. The nomogram predicting recurrence-free survival (RFS) was established by a multivariate Cox regression analysis model and was evaluated by calibration curves, Kaplan-Meier survival curves, time-dependent areas under the receiver operating characteristic (ROC) curves (AUCs), and decision curve analyses in both the training and testing cohorts., Results: Alpha-fetoprotein [hazard ratio (HR) = 1.013, P = 0.002], portal vein tumor thrombosis (HR = 1.833, P < 0.001), ascites (HR = 2.024, P = 0.014), tumor diameter (HR = 1.075, P < 0.001), E-cadherin (HR = 0.859, P = 0.011), EMA (HR = 1.196, P = 0.022), and PCNA (HR = 1.174, P = 0.031) immunohistochemistry scores were found to be independent factors for RFS. The 1-year and 3-year AUCs of the nomogram for RFS were 0.813 and 0.739, respectively. The patients were divided into the high-risk group and the low-risk group by median value which was generated from the nomogram, and Kaplan-Meier analysis revealed that the high-risk group had a shorter RFS than the low-risk group in both the training (P < 0.001) and testing cohorts (P < 0.001)., Conclusions: Our newly developed nomogram integrated clinicopathological data and key gene expression data, and was verified to have high accuracy in predicting the RFS of HCC patients after LR. This model could be used for early identification of patients at high-risk of postoperative recurrence., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Reducing the contact time of droplet impacts on surfaces is crucial for various applications including corrosion prevention and anti-icing. This study aims to explore a novel strategy that greatly reduces contact time using a superhydrophobic mesh surface with multiple sets of mutually perpendicular ridges while minimizing the influence of the impacting location. The effects of the impact Weber numbers and ridge spacing on the characteristics of the impact dynamics and contact time are studied experimentally. The experimental results reveal that, for the droplet impact on mesh surfaces, ridges can segment the liquid film into independently multiple-retracting liquid subunits. The retracted subunits provide the upward driving force, which may promote the splashing or pancake bouncing of droplets. At this point, the contact time has a negligible sensitivity for the impacting position and is significantly reduced by up to 68%. Furthermore, the time, dynamic pressure, and energy criteria for triggering splashing and pancake bouncing are proposed theoretically. This work provides an understanding of the mechanism and the design guidelines for effectively reducing the contact time of the impacting droplet on superhydrophobic surfaces.

Background: Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined., Objectives: To conduct a systematic review on the interaction between caffeine consumption and genetic susceptibility to PD., Methodology: We conducted PubMed and Embase search using terms "Genetic association studies", "Caffeine", "polymorphism" and "Parkinson's disease", from inception till 2023. Of the initial 2391 studies, 21 case-control studies were included. The demographic, genetic and clinical data were extracted and analyzed., Results: We identified 21 studies which involved a total of 607,074 study subjects and 17 gene loci (SNCA, MAPT, HLA-DRA, NOS1, NOS3, GBA, ApoE, BST1, ESR2, NAT2, SLC2A13, LRRK2, NOS2A, GRIN2A, CYP1A2, ESR1, ADORA2A) have been investigated for the effect of gene-caffeine interaction and PD risk. The genes were identified through PD GWAS or involved in caffeine or related metabolism pathways. Based on the genetic association and interaction studies, only MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A have been shown by at least one study to have a positive caffeine-gene interaction influencing the risk of PD., Conclusion: Studies have shown an interaction between caffeine with genetic variants of MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A in modulating the risk of PD. Due to the potential limitations of these discovery/pilot studies, further independent replication studies are needed. Better designed genetic association studies in multi-ancestry and admixed cohorts to identify potential shared or unique multivariate gene-environmental interactions, as well as functional studies of gene-caffeine interactions will be useful., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Genetic association studies have not produced consistent results in restless legs syndrome (RLS)., Objectives: To conduct a systematic review on genetic association studies in RLS to highlight the common gene variants and ethnic differences., Methodology: We conducted Pubmed, Embase, and Cochrane search using terms "Genetic association studies" and "restless legs syndrome" for candidate gene-based studies. Out of the initial 43 studies, 18 case control studies (from 2012 to 2022) were included. Thirteen studies including 10794 Caucasian subjects (4984 RLS cases and 5810 controls) and five studies involving 2009 Asian subjects (796 RLS cases and 1213 controls) were tabulated and analyzed. In addition, three Genome-Wide Association Studies (GWAS) in Asians and Europeans/Caucasians were included for comparisons., Results: In the Asian population, gene variants in BST1, SNCA Rep1, IL1B, BTBD9, and MAP2K5/SKOR1 increased the risk of RLS (odds ratio range 1.2-2.8). In Caucasian populations, examples of variants that were associated with an increased risk of RLS (odds ratio range 1.1-1.9) include those in GABRR3 TOX3, ADH1B, HMOX1, GLO1, DCDC2C, BTBD9, SKOR1, and SETBP1. Based on the meta-analysis of GWAS studies, the rs9390170 variant in UTRN gene was identified to be a novel genetic marker for RLS in Asian cohorts, whereas rs113851554 in MEIS1 gene was a strong genetic factor among the >20 identified gene variants for RLS in Caucasian populations., Conclusion: Our systemic review demonstrates that multiple genetic variants modulate risk of RLS in Caucasians (such as MEIS1 BTBD9, MAP2K5) and in Asians (such as BTBD9, MAP2K5, and UTRN).

While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW-OR 0.93, 95% CI 0.91-0.96, p = 3.12 × 10 -5 ; MR-Egger-OR 0.93, 95% CI 0.88-0.98, p = 1.45 × 10 -2 ; weighted median-OR 0.93, 95% CI 0.89-0.98, p = 2.76 × 10 -3 ; and weighted mode-OR 0.94, 95% CI 0.9-0.98, p = 1.58 × 10 -2 ). The findings were then replicated with another independent GWAS dataset on T1DM (IVW-OR 0.97, 95% CI 0.95-0.99, p = 3.10 × 10 -3 ; MR-Egger-OR 0.96, 95% CI 0.93-0.99, p = 1.08 × 10 -2 ; weighted median-OR 0.97, 95% CI 0.94-0.99, p = 1.88 × 10 -2 ; weighted mode-OR 0.97, 95% CI 0.94-0.99, p = 1.43 × 10 -2 ). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.