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Abstract Aims Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain‐derived neurotrophic factor (BDNF) can add to the HF biomarker scenario, allowing for potentiated efficacy in diagnosis, prognostic stratification, and prediction of patient response to a given therapeutic intervention because BDNF is one of the primary rulers of myocardial function. Yet, whether BDNF is a reliable clinical biomarker awaits clinical validation. Hence, we aimed to answer this relevant question via a systematic review and meta‐analysis of existing studies. Methods and results International databases, including PubMed, Scopus, Embase, and the Web of Science, were comprehensively searched for studies assessing BDNF levels in patients with HF versus non‐HF controls or as a prognostic factor for HF complications. Data were extracted and analysed by random‐effect meta‐analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were computed to pool the results of studies. We included 11 studies in the final review, among which six underwent meta‐analysis. These studies analysed 1420 HF patients, with a mean age of 65.4 ± 11.2 years. Meta‐analysis revealed that patients with HF had significantly lower circulating BDNF levels than healthy controls (SMD −2.47, 95% CI −4.39 to −0.54, P‐value = 0.01). Moreover, patients with higher New York Heart Association functional classification had lower levels of BDNF. Adverse clinical outcomes such as all‐cause mortality and HF rehospitalization were also associated with lower levels of BDNF in individual studies. Conclusions BDNF levels are decreased in patients with HF. Most importantly, we observed an association between lower BDNF levels and poor prognosis in patients with HF. Our study supports BDNF as an easy‐to‐dose diagnostic and prognostic biomarker to be implemented in clinical practice for HF. Further studies are warranted to address this ability specifically.

Abstract An outdoor reduced-scale canyon street was set-up in Angers, France, to study the impact of well-watered trees on urban microclimate and human comfort, with an integrated approach of the soil-plant-atmosphere continuum. Data were acquired during 26 days in summer 2020. The street is oriented north-south, with an aspect ratio of 1. It is organized in three zones: two zones with a central alignment of 5 ornamental apple trees, and one zone without trees. The water inputs are controlled through a drip-irrigation system. Each zone is instrumented to characterise the local microclimate and energy fluxes, the soil water status, and tree leaf temperature. To allow a better understanding of the physical mechanisms at stake in tree services, tree transpiration as well as crown light interception are also quantified, and the trees are characterised in terms of leaf area and crown dimensions. The data can benefit to researchers in urban meteorology and environmental physics. It can also provide reference data to run and evaluate microclimate models, especially regarding plant-atmosphere interactions.

Abstract Background Peripheral artery disease (PAD) is a common disease associated with atherosclerosis, leading to significant mortality and morbidity worldwide. Our study focuses on the association between insulin resistance (IR) and PAD, specifically investigating the triglyceride-glucose index (TyG) as a potential surrogate marker of IR in the context of PAD by pooling the existing studies on this topic. Methods Online databases, including PubMed, Embase, Scopus, and the Web of Science, were searched to find the studies comparing the TyG index in PAD vs. control, reporting the TyG index among PAD severities, and assessing the association of increase in TyG with PAD prevalence. Random-effect meta-analysis was performed to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for TyG level comparison and to calculate pooled odds ratio (ORs) for a 1-unit increase in TyG and higher vs. lower quartile/tertile of TyG association with PAD. Results In the final review, 22 studies comprising 73,168 cases were included. Random-effect meta-analysis showed that patients with PAD had significantly higher levels of the TyG index compared with controls (SMD 0.76, 95%CI 0.65–0.88, P

Abstract The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3′-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.

Abstract Aluminum, due to its high abundance, very attractive theoretical capacity, low cost, low (de−) lithiation potential, light weight, and effective suppression of dendrite growth, is considered as a promising anode candidate for lithium‐ion batteries (LIBs). However, its practical application is hindered due to multiple detrimental challenges, including the formation of an amorphous surface oxide layer, pulverization, and insufficient lithium diffusion kinetics in the α‐phase. These outstanding intrinsic challenges need to be addressed to facilitate the commercial production of Al‐based batteries. The native passivation layer, Al2O3, plays a critical role in the nucleation and reversibility of lithiating aluminum and is thoroughly investigated in this study using high precision electrochemical micro calorimetry. The enthalpy of crystallization of β‐LiAl is found to be 40.5 kJ mol−1, which is in a strong agreement with the value obtained by calculation using Nernst equation (40.04 kJ mol−1). Surface treatment of the active material by the addition of 25 nm of alumina increases the nucleation energy barrier by 83 % over the native oxide layer. After the initial nucleation, the added alumina does not negatively impact the reversibility at 0.1 C rate, suggesting the removal of alumina is not necessary for improving the cyclability of aluminum anode based lithium‐ion batteries. Moreover, the coulombic efficiencies are also found to be slightly higher in the alumina treated samples compared to the untreated ones.

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG’s) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3–30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Abstract DNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, DSB repair pathway choice occurs at the level of DNA end resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate end resection and repair by homologous recombination (HR). However, inability of CDK phospho-mimetic mutants to bypass this cell cycle regulation, suggests that additional cell cycle regulators may be important. Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that end resection and HR require activation by DDK. Mechanistically, DDK phosphorylates at least two resection nucleases in budding yeast: the Mre11 activator Sae2, which promotes resection initiation, as well as the Dna2 nuclease, which promotes resection elongation. Notably, synthetic activation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair pathway selection.

Sex differences are consistently identified in determining the prevalence, manifestation, and response to therapies in several systemic disorders, including those affecting the cardiovascular (CV), skeletal muscle, and nervous system. Interestingly, such differences are often more noticeable as we age. For example, premenopausal women experience a lower risk of CV disease than men of the same age. While at an advanced age, with menopause, the risk of cardiovascular diseases and adverse outcomes increases exponentially in women, exceeding that of men. However, this effect appears to be reversed in diseases such as pulmonary hypertension, where women are up to seven times more likely than men to develop an idiopathic form of the disease with symptoms developing ten years earlier than their male counterparts. Explaining this is a complex question. However, several factors and mechanisms have been identified in recent decades, including a role for sex hormones, particularly estrogens and their related receptors. Furthermore, an emerging role in these sex differences has also been suggested for β-adrenergic receptors (βARs), which are essential regulators of mammalian physiology. It has in fact been shown that βARs interact with estrogen receptors (ER), providing further demonstration of their involvement in determining sexual differences.Based on these premises, this review article focused on the β3AR subtype, which shows important activities in adipose tissue but with new and interesting roles in regulating the function of cardiomyocytes and vascular cells. In detail, we examined how β3AR and ER signaling are intertwined and whether there would be sex- and age-dependent specific effects of these receptor systems.

Abstract Background An essential relationship between insulin resistance (IR) and atrial fibrillation (AF) has been demonstrated. Among the methods used to assess IR, the triglyceride-glucose (TyG) index is the more straightforward, dimensionless, and low-cost tool. However, the possible usage of this index in clinical practice to predict and diagnose AF has yet to be determined and consolidated. Objective and rationale Herein, we performed a systematic review and meta-analysis to assess the association between the TyG index and AF. Methods Databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched for studies evaluating the TyG index in AF. The inclusion criteria were observational studies investigating AF and TyG index correlation in individuals older than 18 years, while preclinical studies and those without the relevant data were excluded. Random effect meta-analyses comparing TyG levels between AF and non-AF cases, AF recurrence after radiofrequency ablation, and post-procedural AF were performed using standardized mean differences (SMD) with their matching 95% confidence intervals (CIs). Results Our screening identified nine studies to be analyzed, including 6,171 participants including 886 with AF. The meta-analysis demonstrated that the TyG index resulted higher in patients with AF than non-AF counterparts (SMD 1.23, 95% CI 0.71 to 1.75, I 2 98%, P

Abstract Background Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index. Methods Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index. Results Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P

Abstract Background Insulin resistance (IR) is a major metabolic disorder observed in heart failure (HF) and is tightly associated with patients’ poor prognosis. The triglyceride-glucose index (TyG) has been proposed as a surrogate marker of IR in HF. Yet, whether TyG is a reliable clinical marker is still under debate. Hence, we aimed to respond to this relevant question via a systematic review and meta-analysis of existing studies. Methods A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science to find studies investigating the TyG index in patients with HF or its association with the incidence of HF. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were pooled through random-effect meta-analysis. HRs were calculated using TyG as a continuous variable (1 unit increase) and by comparing the group with the highest TyG to the lowest TyG group. Results Thirty studies, involving 772,809 participants, were included in this systematic review. Meta-analysis of seven studies comparing the highest-TyG to the lowest-TyG group showed a significantly increased risk of HF in the former group (HR 1.21, 95% CI 1.14 to 1.29, P

Objective To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.Methods The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (