Assessing the effect of bovine MSTN variants on pre‐m RNA splicing

Abstract The myostatin protein is a potent negative regulator of skeletal muscle growth encoded by the MSTN gene. MSTN loss‐of‐function variants lead to a particular cattle phenotype characterized by an increase in skeletal muscle mass, known as “double muscling” or “double muscled”. However, most of the MSTN causal variants that have been linked to this phenotype lack experimental validation. This is the case, for example, for the five missense MSTN variants reported to be causal according to the Online Mendelian Inheritance in Animals. RNA splicing plays a major role in regulating gene expression; therefore, exploring the effects of variants on RNA splicing may provide relevant information on their functional impact. Here, we have set up a full‐length gene assay (FLGA) to functionally assess MSTN splicing variants, and we have used it to test the five missense variants plus a well‐described deep intronic splicing variant as a positive control. We also evaluated the performances of SpliceAI and Pangolin, two deep learning‐based splice predictors, to identify potential splicing effects of these six variants. Our FLGA system performed well and showed that none of the missense variants has an effect on splicing, unlike the positive control. For each variant, splicing program predictions were perfectly concordant with the effect observed in the FLGA. We have produced a relevant and powerful assay to analyze MSTN splicing variants in cattle. SpliceAI and Pangolin may be efficiently used to screen large datasets of MSTN variants and sort the best candidates prior to experimental validation using an FLGA.

Process intensification of CO 2 chemical absorption in a conjugated double‐helix cross minichannel absorber

Abstract This paper presents a novel design of miniaturized absorber for carbon capture, featuring a conjugated double‐helix cross (Codohec) multi‐minichannel structure. A lab‐scale Codohec module with four minichannels was fabricated, andCO 2chemical absorption experiments were conducted using monoethanolamine (MEA) aqueous solution under varied gas and liquid flowrates and MEA concentration conditions. Flow visualization revealed that the unique Codohec design induces diverse bubble morphologies (e.g., swirling, splitting, switching, collision, and recombination), significantly enhancing the two‐phase mass transfer. Results also demonstrated that the Codohec module achieves aCO 2processing capacity of up to 6.57 × 10 − 6kg s −1 while maintaining a high overall mass transfer coefficient of 2.75 s −1 , and with an energy consumption below 4.24 W kg −1 . These findings highlight the potential of miniaturized devices for efficient carbon capture with enhanced mass transfer, high throughput and energy efficiency, offering a promising solution for large‐scale industrial applications.

Use of cimetidine to enhance systemic acyclovir concentrations in patients with ineffective suppressive therapy for recurring herpes simplex virus infections: A novel purpose for an old drug

Herpes simplex virus (HSV) may cause recurring oral or genital ulcers. We report a series of patients nonresponsive to suppressive valacyclovir therapy, explained by subtherapeutic acyclovir plasma levels. After a dose increase, or in some patients only after concomitant prescription of cimetidine, adequate levels were reached associated with significant clinical improvement.

Risk of major congenital anomalies and beta‐blockers: A comparative study from the EFEMERIS database

Aims To evaluate if exposure to beta‐blockers during the first trimester of pregnancy increases the risk of congenital anomaly. Methods An observational comparative study was carried out. This study was conducted using EFEMERIS, a medico‐administrative database. We included women who had a pregnancy between 2004 and 2021 registered in EFEMERIS. Comparison of women receiving beta‐blockers during the first trimester of pregnancy with those receiving calcium channel blockers and with women unexposed to antihypertensive medications. Logistic regression models adjusted for relevant confounders were used to estimate the adjusted odds ratios (ORa) for major congenital anomalies. We calculated the ajusted Odds Ratio (ORa) and its 95% confidence intervals (CI) for major congenital anomalies. Results Data from 1813 pregnant women (1%) exposed to beta‐blockers, 2903 (1.6%) exposed to calcium channel blockers and 172 284 unexposed to any antihypertensive medication were compared. Multivariate analyses showed a statistically significant increased risk of major congenital anomalies in fetuses/children exposed to beta‐blockers (ORa[95% CI] = 1.56 [1.07–2.18]) compared with unexposed group. However, this increased risk was not observed when comparing with women exposed to calcium channel blockers (ORa[95% CI] = 0.71 [0.29–2.15]). An increased risk of major congenital anomalies was also observed in fetuses/children exposed to labetalol compared with those unexposed to antihypertensive medications (ORa [95% CI] = 2.00 [1.06–3.40]), but not when compared with those exposed to calcium channel blockers (ORa [95% CI] = 1.06 [0.37–3.48]). Conclusions This study found no increased risk of major congenital anomalies in women exposed to beta‐blockers compared with those exposed to calcium channel blockers in early pregnancy.

Epidemiology of Colorectal Cancer in French Guiana From 2003 to 2017

ABSTRACT Background Colorectal cancer (CRC) is a major global public health issue, with 1.9 million new cases and 904,000 deaths in 2022. French Guiana is an overseas territory located in the Amazon region with many unique features, but data on CRC in this area remains limited. The objective of this work was to evaluate the prognosis of CRC and the associated factors in French Guiana. Methods We used the French Guiana Cancer Registry database for the period 2003 to 2017. A survival analysis was conducted. Additionally, standardized incidence and mortality rates were calculated and mapped using QGIS. Results During this period, 457 patients were included, with a male predominance (54.7%). The median age was 62 years. One‐third of the population was born abroad. The 5‐year overall survival rate was 47.4% (95% CI [42.1–53.5]). Female sex was associated with better 5‐year survival: 55% [47.2–64.0] vs. 41% [35.0–50.0] for males ( p  = 0.03). In the multivariate analysis, sex and place of birth were independently associated with overall survival (HR = 0.7 [0.5–0.9], p  = 0.002 for females; HR = 1.5 [1.1–2.1], p  = 0.005 for those born abroad). The age‐standardized incidence rate, adjusted to the world population, was 22.6 per 100,000 in men and 17.2 per 100,000 in women. Standardized mortality was 14 per 100,000 for men and 8.5 per 100,000 for women. Conclusion In French Guiana, the 5‐year survival rate for CRC was lower than in mainland France. Being born abroad was associated with poorer survival, reflecting health inequalities linked to socio‐economic vulnerability in this territory, despite a lower overall incidence of CRC.

Isolation, RP‐UHPLC‐ESI‐LIT‐Orbitrap‐MS/MS‐Based Metabolic Profiling and Anticandidal Activity of the Root and Leaf Secondary Metabolites of Monotes Kerstingii Gilg (Dipterocarpaceae)

ABSTRACT The anticandidal activity of Monotes kerstingii leaf and root crude extracts was evaluated against five clinical Candida isolates: C. albicans , C. parapsilosis , C. krusei , C. glabrata and C. tropicalis . Extracts from both organs displayed Minimal Inhibitory Concentrations (MICs) ranging from 3.9 to 2000 µg/mL. Out of the five Candida species, the leaf hydroethanolic extract (EMKL) was the most active with MIC values of 3.9, 15.6 and 31.5 µg/mL on C. krusei, C. parapsilosis and C. albicans , respectively. The chemical investigation of these extracts led to the characterization of six previously undescribed metabolites, including a glycosylated stilbene: kerstingioside ( 1 ), three cis stilbene‐coumarins: cis ‐kerstilbcoumarin A–C ( 2–4 ) among which two as inseparable cis / trans ‐mixtures, one flavanone: kerstingiiflavanone ( 5 ) and one fatty acid glycoside, monestoside B ( 6 ), alongside with 22 known compounds. The distribution of the annotated metabolites in the roots and leaves was confirmed by comprehensive RP‐UHPLC‐Orbitrap‐MS and MS/MS analysis. In addition, all the isolated compounds were screened for their anticandidal activity. Stilbene 7 was the most active constituent, with MICs of 7.8, 15.6, and 15.6 µg/mL against C. albicans , C. krusei , and C. parapsilosis , respectively, while compounds 14 and 15 exhibited only moderate activity.

Staphylococcal SplA and SplB Serine Protease Allelic Variants Exhibit Different Substrate Specificities

Staphylococcus aureus is an opportunistic pathogen that is persistently colonizing nearly 30% of the human population and can cause life‐threatening infections. S. aureus secretes a variety of virulence factors, such as a set of extracellular serine protease‐like proteins (Spls). Spls are expressed by most clinical isolates of S. aureus , but their pathophysiological substrates and role during infection are largely unknown. Pathogens use allelic variation of virulence factors to allow an adaption to different host cells and their defense mechanisms. The differences of these variants are marginally characterized so far. Here, we performed a biochemical characterization of selected allelic variants of the S. aureus SplA and SplB. Our data suggests different variants show differences in their stability, enzymatic activity, and substrate specificity. For the recently identified Spl target proteins RickULP and SseL, different cleavage patterns were observed, upon treatment with different Spl allelic variants. One SplB variant strongly differed in its substrate recognition at the P3/P4 position, more closely resembling SplE than SplB wildtype in its substrate selectivity. Our data provide valuable insights into the evolution of bacterial virulence factors and highlight the importance of including allelic variation of virulence factors to fully understand their role in host–pathogen interaction.

Particle Size Effects on Dynamic Behavior of Heated Spheroidal Particles in Shear Flow

ABSTRACT This work investigates the dynamics of prolate particles suspended in shear flows through four‐way direct numerical simulations, considering both isothermal and non‐isothermal. To achieve this, we adopt a hybrid numerical framework that integrates the lattice Boltzmann method, a finite‐difference scheme, the immersed boundary method, and the discrete element method. The analysis focuses on how heat transfer and particle size influence particle dynamic motion and rotational behavior, including the evolution toward the final equilibrium state, the characteristics of that equilibrium, rotational velocity, and orientation‐induced oscillations. The findings show that the confinement ratio, defined as the particle's major radius relative to the channel width, strongly governs both the time required for a particle to reach equilibrium and the vertical position of that equilibrium, as well as the particle's rotational speed and its oscillation around the equilibrium position.

New Adrenaline Devices for Treating Anaphylaxis: Results of a Joint Survey From the European Anaphylaxis Registry and the Allergy‐Vigilance Network

ABSTRACT Background Adrenaline auto‐injectors (AAI) are underused to treat anaphylaxis. New adrenaline devices are currently under investigation or have been recently marketed. This survey aimed to assess the perspectives from allergy‐trained physicians regarding the AAI use and their expectations about new adrenaline devices. Methods This electronic survey was created by the European Anaphylaxis Registry and Allergy‐Vigilance Network. It was proposed to their participants (March–April 2025) who were asked to rank their responses on a 11‐point Likert scale (0: ‘not important’ to 10: ‘very important’). Results are presented as median with interquartile range. Results One hundred and seventy‐five physicians (allergists, 59.4%) participated in this survey. There were only few barriers to AAI prescriptions. Up to 65% of participants estimated the following features as very important for new adrenaline devices: prolonged shelf life (9 [7–10]), improved storage conditions (9 [5–9]), detailed pharmacokinetic‐pharmacodynamic data (8 [7–10]), optimised dose ranging (8 [7–10]), availability in public spaces (8 [7–10]), devices easy to carry (8 [7–9]), needle‐free device (8 [6–10]). A history of anaphylaxis treated with > 1 adrenaline injection (7 [4–9]) or admitted to intensive care unit (7 [3–8]) were reported as the most important barriers to use new adrenaline devices. 75% of participants felt that recommendations from allergy societies and more clinical data are important measures to reduce barriers to new adrenaline devices. Conclusions Our data provide insights from allergy‐trained physicians into AAI limitations and expectations on new adrenaline devices. To advance them, input from allergy societies and more clinical data from anaphylaxis patients are needed.

Plasma cell‐free DNA markers predict occult metastases in patients with resectable pancreatic ductal adenocarcinoma