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The Tauc method is the conventional technique for estimating the accurate optical bandgap energy of semiconductors using UV–Vis spectroscopy. The proper bandgap is usually determined by directly extrapolating the linear region of the optical spectrum to the horizontal axis of the Tauc plot αhv1/r vs. hv. However, the use of unconventional Tauc plots, such as α1/r vs. hv, A1/r vs. hv, and FR∞ vs. hv are also found in the literature. This raises a debate as to whether these nontraditional methods can produce the correct bandgap value. These uncommon methods appear frequently even in recent papers published in reputable journals, and therefore, have raised concern to investigate the likelihood of obtaining the correct bandgap value using the unusual methods. Results showed that the plots of α1/r vs. hv, and A1/r vs. hv yielded bandgap values that were consistent with those deduced from the universal Tauc plot, whereas the other methods failed.

Not available.

Although coppice forests represent a significant part of the European forest area, especially across southern Countries, they received little attention within the Sustainable Forest Management (SFM) processes and scenarios, whose guidelines have been mainly designed to high forests and national scale. In order to obtain “tailored” information on the degree of sustainability of coppices on the scale of the stand, we evaluated (i) whether the main coppice management options result in different responses of the SFM indicators, and (ii) the degree to which the considered SFM indicators were appropriate in their application at stand level. The study considered three different management options (Traditional Coppice TC, coppice under Natural Evolution NE, and coppice under Conversion to high forest by means of periodical thinning CO). In each of the 43 plots considered in the study, which covered three different European Forest Types, we applied a set of eighteen “consolidated” SFM indicators, covering all the six SFM Criteria (FOREST EUROPE, 2020) and, additionally, tested other sixteen novel indicators shaped for agamic forests and/or applicable at stand level. Results confirmed that several consolidated indicators related to resources status (Growing stock and Carbon stock), health (Defoliation and Forest damage), and socio-economic functions (Net revenue, Energy and Accessibility) were highly appropriate for evaluating the sustainability of coppice at stand level. In addition, some novel indicators related to resources status (Total above ground tree biomass), health (Stand growth) and protective functions (Overstorey cover and Understorey cover) proved to be highly appropriate and able to support the information obtained by the consolidated ones. As a consequence, a subset of consolidated SFM indicators, complemented with the most appropriate novel ones, may represent a valid option to support the evaluation of coppice sustainability at stand level. An integrated analysis of the SFM indicators showed that NE and CO display significant higher environmental performances as compared with TC. In addition, CO has positive effects also on socio-economic issues, while TC -which is an important cultural heritage and a silvicultural option that may help to keep local communities engaged in forestry – combines high wood harvesting rates with dense understory cover. Overall, each of the three management options showed specific sustainability values; as a consequence, their coexistence at a local scale and in accordance with the specific environmental conditions and the social-economic context, is greatly recommended since it may fulfill a wider array of sustainability issues.

We investigate the transition of the solar wind turbulent cascade from MHD to sub‐ion range by means of a detailed comparison between in situ observations and hybrid numerical simulations. In particular, we focus on the properties of the magnetic field and its component anisotropy in Cluster measurements and hybrid 2D simulations. First, we address the angular distribution of wave vector in the kinetic range between ion and electron scales by studying the variance anisotropy of the magnetic field components. When taking into account a single-direction sampling, like that performed by spacecraft in the solar wind, the main properties of the fluctuations observed in situ are also recovered in our numerical description. This result confirms that solar wind turbulence in the sub‐ion range is characterized by a quasi-2D gyrotropic distribution of k-vectors around the mean field. We then consider the magnetic compressibility associated with the turbulent cascade and its evolution from large-MHD to sub‐ion scales. The ratio of field aligned to perpendicular fluctuations, typically low in the MHD inertial range, increases significantly when crossing ion scales and its value in the sub‐ion range is a function of the total plasma beta only, as expected from theoretical predictions, with higher magnetic compressibility for higher beta. Moreover, we observe that this increase has a gradual trend from low to high beta values in the in situ data; this behavior is well captured by the numerical simulations. The level of magnetic field compressibility that is observed in situ and in the simulations is in fairly good agreement with theoretical predictions, especially at high beta, suggesting that, in the kinetic range explored, the turbulence is supported by low-frequency and highly oblique fluctuations in pressure balance, like kinetic Alfvén waves or other slowly evolving coherent structures. The resulting scaling properties as a function of the plasma beta and the main differences between numerical and theoretical expectations and in situ observations are also discussed.

BACKGROUND: Little is known about the morbidity associated with laparoscopic complete excision of endometriosis in terms of urinary, digestive and sexual function. METHODS: We performed a prospective non-randomized study in 45 patients with laparoscopic complete excision of all detectable foci of endometriosis with segmental bowel resection using a non nerve-sparing technique (control group–group A n = 20) and a nerve-sparing technique (case group–group B n = 25). At initial gynaecological evaluation, and at follow-up details on dysmenorrhoea, pelvic pain, dyspareunia and dyschezia were evaluated using an interview-based questionnaire (10-point analogue rating scale: 0 = absent, 10 = unbearable). RESULTS: The mean (±SD) follow-up period was 15.3 ± 10 months (range, 8.8–23 months) for group A and 3.5 ± 2.1 months (range, 0.3–5.2 months) for group B. In the immediate postoperative course, in group A three women required blood transfusion vs seven women in group B (P = 0.003). The median time to resume the voiding function was significantly shorter in group B (12.5 vs 3.0 days; P < 0.01). At the time of follow-up a higher proportion of patients in group B were ‘very satisfied’ than those in group A (87.7% vs 59.0%, P = 0.013). CONCLUSIONS: Laparoscopic nerve-sparing complete excision of endometriosis seems to be feasible and offers good results in terms of bladder morbidity reduction with apparently higher satisfaction than classical technique. Larger series with longer follow-up are needed to confirm our results. [ABSTRACT FROM AUTHOR]

INTRODUCCIÓN Durante el proceso de congelación y descongelación al que es sometido el semen bovino, ocurren diferentes formas de lesiones celulares, lo que ocasiona una disminución en la motilidad, viabilidad y la capacidad de fertilización del esperma después de la inseminación (Chaveiro, Machado, Frijters, Engel, & Woelders, 2006). Uno de los principales factores que reduce la viabilidad del espermatozoide, es la formación de hielo intracelular, por tal razón la composición del diluyente y la naturaleza del crioprotector de semen podrían ayudar a reducir este daño. El crioprotector utilizado con más frecuencia es el glicerol, que debe ser usado a bajas concentraciones (menos del 4%) debido a su potencial de toxicidad (Bhur, Fiser, Bailey, & Curtis, 2001), por tal razón, en la actualidad se ha investigado la utilización de otros agentes crioportectores menos dañinos, tales como los agentes no permeables dentro de estos azucares como la rafinosa, trehalosa y sacarosa, estos favorecen la excreción de agua fuera de la célula, a fin de disminuir la formación de cristales de hielo intracelular. La trehalosa es un disacárido no reductor, es producida por diversos organismos en respuesta a condiciones de estrés como: la deshidratación, temperaturas extremas y choque osmótico (Cerrutti, Segovia de Huergo, Galvagno, Schebor, & Buera, 2000). Además, es un estabilizador de biomoléculas, incluyendo proteínas. De Leeuw, De Leeuw, Den Daas, Colenbrander, & Verkleij (1993) investigaron el efecto de la adición de trehalosa y sacarosa a un medio de congelación de semen de toro y encontraron que la sacarosa puede tener un pequeño efecto positivo en la supervivencia del esperma, en estudios hechos por Woelders, Matthijs, & Engel (1997) se encontró que la adición de sacarosa o trehalosa contribuye a la protección del espermatozoide dependiendo la osmolaridad del medio. Por lo tanto, el objetivo del presente estudio es determinar el efecto de los agentes crioprotectores no permeables tales como trehalosa, sacarosa, rafinosa y lactosa, en combinación con glicerol, sobre las características físicas del semen de toro. Específicamente, se pretende comparar el efecto sobre las características físicas de los espermatozoides bovinos de un crioprotector de los agentes no permeables de trehalosa y sacarosa frente a un diluyente comercial.

Magnetic reconnection provides the primary source for explosive energy release, plasma heating, and particle acceleration in many astrophysical environments. The last years witnessed a revival of interest in the MHD tearing instability as a driver for efficient reconnection. It has been established that, provided the current sheet aspect ratio becomes small enough (a/L ∼ S−1/3 for a given Lundquist number S ≫ 1), reconnection occurs on ideal Alfvén timescales and becomes independent of S. Here we investigate, by means of two-dimensional simulations, the ideal tearing instability in both the MHD and the Hall-MHD regime, which is appropriate when the width of the resistive layer δ becomes comparable to the ion inertial length di. Moreover, we study in detail the spontaneous development and reconnection of secondary current sheets, which for high S naturally adjust to the ideal aspect ratio and hence their evolution proceeds very rapidly. For moderate low S, the aspect ratio tends to the Sweet–Parker scaling (a/L ∼ S−1/2). When the Hall term is included, the reconnection rate of this secondary nonlinear phase is enhanced and, depending on the ratio di/δ, can be two times larger with respect to the pure MHD case, and up to 10 times larger than the linear phase. Therefore, the evolution of the tearing instability in thin current sheets in the Hall-MHD regime naturally leads to an explosive disruption of the reconnecting site and to energy release on super-Alfvénic timescales, as required to explain space and astrophysical observations. [ABSTRACT FROM AUTHOR]

Magnetic reconnection in laboratory, space and astrophysical plasmas is often invoked to explain explosive energy release and particle acceleration. However, the timescales involved in classical models within the macroscopic MHD regime are far too slow to match the observations. Here we revisit the tearing instability by performing visco-resistive two-dimensional numerical simulations of the evolution of thin current sheets, for a variety of initial configurations and of values of the Lunquist number S, up to 107. Results confirm that when the critical aspect ratio of S1/3 is reached in the reconnecting current sheets, the instability proceeds on ideal (Alfvénic) macroscopic timescales, as required to explain observations. Moreover, the same scaling is seen to apply also to the local, secondary reconnection events triggered during the nonlinear phase of the tearing instability, thus accelerating the cascading process to increasingly smaller spatial and temporal scales. The process appears to be robust, as the predicted scaling is measured both in inviscid simulations and when using a Prandtl number P  =  1 in the viscous regime. [ABSTRACT FROM AUTHOR]

Colloidal suspensions of oxocarbon-encapsulated gold nanoparticles have been synthesized in a one-step procedure by pulsed-laser ablation (PLA) at 532 nm of a solid gold target placed in aqueous solution containing CO2 absorbers, but without any stabilizing agent. Multi-wavelength surface enhanced Raman spectroscopy allows the identification of adsorbed amorphous carbon and graphite, Au-carbonyl, Au coordinated CO2-derived bicarbonates/carbonates and hydroxyl groups around the AuNPs core. Scanning electron microscopy, energy dispersive x-ray analysis and high resolution transmission electron microscopy highlight the organic shell structure around the crystalline metal core. The stability of the colloidal solution of nanocomposites (NCs) seems to be driven by solvation forces and is achieved only in neutral or basic pH using monovalent hydroxide counter-ions (NaOH, KOH). The NCs are characterized by a blue shift of the localized surface plasmon resonance (LSPR) band typical of metal-ligand stabilization by terminal π-back bonding, attributed to a core charging effect caused by Au-carbonyls. Total organic carbon measurements detect the final content of organic carbon in the colloidal solution of NCs that is about six times higher than the value of the water solution used to perform PLA. The colloidal dispersions of NCs are stable for months and are applied as analytical probes in amino glycoside antibiotic LSPR based sensing. [ABSTRACT FROM AUTHOR]

We investigate properties of a solar wind-like plasma, including a secondary alpha particle population exhibiting a parallel temperature anisotropy with respect to the background magnetic field, using linear and quasi-linear predictions and by means of one-dimensional hybrid simulations. We show that anisotropic alpha particles can drive a parallel fire hose instability analogous to that generated by protons, but that, remarkably, can also be triggered when the parallel plasma beta of alpha particles is below unity. The wave activity generated by the alpha anisotropy affects the evolution of the more abundant protons, leading to their anisotropic heating. When both ion species have sufficient parallel anisotropies, both of them can drive the instability, and we observe the generation of two distinct peaks in the spectra of the fluctuations, with longer wavelengths associated to alphas and shorter ones to protons. If a non-zero relative drift is present, the unstable modes propagate preferentially in the direction of the drift associated with the unstable species. The generated waves scatter particles and reduce their temperature anisotropy to a marginally stable state, and, moreover, they significantly reduce the relative drift between the two ion populations. The coexistence of modes excited by both species leads to saturation of the plasma in distinct regions of the beta/anisotropy parameter space for protons and alpha particles, in good agreement with in situ solar wind observations. Our results confirm that fire hose instabilities are likely at work in the solar wind and limit the anisotropy of different ion species in the plasma. [ABSTRACT FROM AUTHOR]

We study the linear and nonlinear evolution of the tearing instability on thin current sheets by means of two-dimensional numerical simulations, within the framework of compressible, resistive MHD. In particular we analyze the behavior of current sheets whose inverse aspect ratio scales with the Lundquist number S as . This scaling has been recently recognized to yield the threshold separating fast, ideal reconnection, with an evolution and growth that are independent of S provided this is high enough, as it should be natural having the ideal case as a limit for . Our simulations confirm that the tearing instability growth rate can be as fast as , where is the ideal Alfvénic time set by the macroscopic scales, for our least diffusive case with . The expected instability dispersion relation and eigenmodes are also retrieved in the linear regime, for the values of S explored here. Moreover, in the nonlinear stage of the simulations we observe secondary events obeying the same critical scaling with S, here calculated on the local, much smaller lengths, leading to increasingly faster reconnection. These findings strongly support the idea that in a fully dynamic regime, as soon as current sheets develop, thin, and reach this critical threshold in their aspect ratio, the tearing mode is able to trigger plasmoid formation and reconnection on the local (ideal) Alfvénic timescales, as required to explain the explosive flaring activity often observed in solar and astrophysical plasmas. [ABSTRACT FROM AUTHOR]

Background: Functional motor disorders (FMDs) are prevalent and highly disabling conditions among young adults, leading to reduced independence. Despite advancements in diagnosis and treatment, the economic burden of FMDs remains largely unknown., Objective: This study evaluates the impact of accurate FMDs diagnosis on direct healthcare costs within the Italian National Health System by comparing healthcare utilization and costs before and after diagnosis., Methods: This before-after study included 40 patients with a definite diagnosis of FMDs. Retrospective data on healthcare utilization, including diagnostic tests, specialist visits, hospitalizations, Emergency Room (ER) visits, and rehabilitation services, were collected from diaries and documents two years before and after diagnosis., Results: Healthcare direct costs decreased by 67%, from an average of €4,467 [95% CI 3,604-5,329] to €1,461 [95% CI 945-1,976] after diagnosis. Hospitalization costs fell from €2,618 [95% CI 1,899-3,336] to €492 [95% CI 162-821], and ER costs dropped from €403 [95% CI 177-628] to €43 [95% CI 6-78]. Diagnostic procedure costs decreased significantly, from €403 [95% CI 177-628] to €43 [95% CI 6-78]. Specialist visit costs remained unchanged. Rehabilitation costs increased from €371 [95% CI 194-547] to €635 [95% CI 318-915], but this rise was not statistically significant., Conclusions: Accurate diagnosis of FMDs significantly reduces healthcare costs by minimizing unnecessary tests, hospitalizations, and ER visits while emphasizing rehabilitation. This highlights the economic and clinical benefits of improved diagnostic accuracy and specific multidisciplinary intervention. Investing in cost-effective diagnostic tools is crucial for earlier diagnosis and reducing delays., Competing Interests: Declarations Ethics approval All investigations were carried out in accordance with the Helsinki Declaration and its later amendments. Approval was obtained from the local Institutional Ethics Committee (Project Number 132 1757CESC). Consent to participate The study was incorporated within the Verona dataset of RI-FMDs, so informed consent for participation in the registry sufficed. Competing interests The authors declare no competing interests., (© 2024. Fondazione Società Italiana di Neurologia.)

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and the identification of novel druggable targets is urgently needed. In previous work, we identified 15 deregulated genes highly expressed in MPM tissues and correlated with a poor prognosis. Here, we validated these findings on an independent dataset of 211 MPM patients (EGA, EGAD00001001915) and on a panel of MPM cell lines. Furthermore, we carried out in vitro gene silencing followed by proliferation, cytotoxicity, caspase, and migration assays to define whether these targets could be cancer-driver genes. We ended up with three novel candidates (i.e., BAG2, MAD2L1, and MDK), whose encoded proteins could be exploited as druggable targets. Moreover, of novelty, immunohistochemistry analysis on tissues revealed that the overexpression of BAG2 and MAD2L1 could differentiate MPM from RMP patients. Furthermore, when we tested Neratinib (an inhibitor of MAD2L1) and iMDK (an inhibitor of MDK) we found that they are effective on MPM cells, in part phenocopying the effects of MAD2L1 and MDK gene silencing. In summary, in the present work, we report that BAG2, MAD2L1, and MDK are bona fide cancer-driver genes for MPM worth of further studies., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The collection and analysis of human tissue samples were conducted in accordance with the Declaration of Helsinki and with approvals by the Ethical Committee of the Capital Region of Denmark (Protocol No. H32011135-57379) and the Danish Data Protection Agency (Protocol No. DT2016414917), as previously described [15]. Additionally, the Danish Registry for Use of Tissue was checked to ensure that patients included in the study had not refused the usage of their tissue samples for research purposes., (© 2024. The Author(s).)

The European Commission asked EFSA to update its 2012 risk assessment on brominated phenols and their derivatives in food, focusing on five bromophenols and one derivative: 2,4,6-tribromophenol ( 2,4,6-TBP ), 2,4-dibromophenol ( 2,4-DBP ), 4-bromophenol ( 4-BP ), 2,6-dibromophenol ( 2,6-DBP ), tetrabrominated bisphenol S ( TBBPS ), tetrabromobisphenol S bismethyl ether ( TBBPS-BME ). Based on the overall evidence, the CONTAM Panel considered in vivo genotoxicity of 2,4,6-TBP to be unlikely. Effects in liver and kidney were considered as the critical effects of 2,4,6-tribromophenol ( 2,4,6-TBP ) in studies in rats. A BMDL 10 of 353 mg/kg body weight (bw) per day for kidney papillary necrosis in male rats was identified and was selected as the reference point for the risk characterisation. The derivation of a health-based guidance value was not considered appropriate due to major limitations in the toxicological database. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Around 78,200 analytical results for 2,4,6-TBP in food were used to estimate dietary exposure for the European population. Considering the resulting MOE values, all far above an MOE of 6000 that does not raise a health concern, and accounting for the uncertainties affecting the exposure and hazard assessments, the CONTAM Panel concluded with at least 95% probability that the current dietary exposure to 2,4,6-TBP does not raise a health concern. Due to lack of occurrence data, no risk assessment could be performed for breastfed or formula-fed infants. No risk characterisation could be performed for any of the other brominated phenols and derivatives included in the assessment, due to lack of data both on the toxicity and occurrence., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BID rs9604789 variant with an increased risk of developing the disease (OR Meta  = 1.31, p = 9.67 × 10 -6 ). We also confirmed the association of TP63 rs1515496 and TP63 rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10 -8 and OR = 1.16, p = 2.74 × 10 -5 ). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63 rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10 -4 and p = 1.56 × 10 -3 ), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10 -4 ). These results were in agreement with research suggesting that the TP63 rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Cold stress represents one of the major constraints for agricultural systems and crops productivity, inducing a wide range of negative effects. Particularly, long-term cold stress affects lipid metabolism, modifying the lipids/proteins ratio, the levels of phospholipids and glycolipids, and increasing lipids' unsaturation in bio-membranes. Glucose-6-phosphate dehydrogenase (G6PDH) reported prominent roles as NADPH suppliers in response to oxidative perturbations. Cytosolic G6PDH was suggested as the main isoform involved in cold stress response, while a down-regulation of the chloroplastic P1-G6PDH was observed. We thus investigated an Arabidopsis mutant defective for the P1-G6PDH (KO-P1) using integrated approaches to verify a possible role of this isoform in low temperature tolerance. KO-P1 genotype showed an improved tolerance to cold stress, highlighting a better photosynthetic efficiency, a reduction in stress markers content and a different regulation of genes involved in stress response. Intriguingly, the lack of P1-G6PDH induced modification in the levels of the main fatty acid and lipid species affecting the morphology of chloroplasts and mitochondria, which was restored under cold. Globally, these results indicate a priming effect induced by the absence of P1-G6PDH able to improve the tolerance to abiotic stress. Our results suggest novel and specific abilities of P1-G6PDH, highlighting its central role in different aspects of plant physiology and metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Neurogenic bowel dysfunction is a frequent consequence of spinal cord injury/disease (SCI/D). A colostomy is considered when conservative treatments fail [1, 2]. In the last year we observed several SCI/D persons with colostomy, admitted to our institution with multiple complications., Case Presentation: We present four cases of SCI/D persons treated with Hartmann's procedure and admitted to our institution for pressure ulcer (PU) treatment. All patients underwent PU surgery with good results. All patients reported a subjective good evacuation setting. No one assumed laxative therapies at home. At admission, all patients underwent abdominal radiography that showed an important constipation, with cases of sub-occlusion or complete occlusion with gastroparesis. One person presented a parastomal, strangulated hernia and underwent hernia reduction and patch positioning around the stoma. During hospital stay, bowel management required an important administration of laxatives and frequent, almost daily, stoma washes., Discussion: Some considerations must be made regarding the use of traditional techniques in SCI/D people, such as Hartmann's, leaving a large part of the colon and the anatomical position of the stoma itself represent limitations to fecal progression and may cause constipation. A specific approach, tailored on the SCI/D patients' characteristics, such as the one described by our group, should be considered. Even if colostomy has been performed, appropriate therapies and health education on how to manage the stoma are fundamental to prevent complications., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Malignant Pleural Mesothelioma (MPM) is a rare malignancy with a poor prognosis. Current therapies are unsatisfactory and novel cures are urgently needed. In a previous drug screening, we identified thonzonium bromide (TB) as one of the most active compounds against MPM cells. Since the biological effects of TB are poorly known, in this work we departed from some hints of previous studies and investigated several hypotheses. Moreover, we evaluated the efficacy of TB in an in vivo xenograft rodent model., Methods: In vitro assessment was made on five MPM (Mero-14, Mero-25, Ren, NCI-H28, MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A). We evaluated TB ability to affect proliferation, apoptosis, mitochondrial functions and metabolism, and the mevalonate pathway. In vivo assay was carried out on MPM-xenograft NOD-SCID mice (4 mg/kg delivered intraperitoneally, twice a week for 4 weeks) and the overall survival was analysed with Kaplan-Meier curves., Results: After TB treatment, we observed the suppression of ERK 1/2 phosphorylation, the increase of BAX expression and p38 phosphorylation. TB affected Ca 2+ homeostasis in both mitochondrial and cytosolic compartments, it regulated the mitochondrial functioning, respiration, and ATP production as well as the mevalonate pathway. The in vivo study showed an increased overall survival for TB treated group vs. vehicle control group (P = 0.0076)., Conclusions: Both in vitro and in vivo results confirmed the effect of TB on MPM and unravelled novel targets with translational potential., (© 2024. The Author(s).)

Introduction: The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3 ), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC)., Materials and Methods: To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome., Results: Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization., Conclusion: Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies., 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., (Copyright © 2024 Silvestri, Zallocco, Corrado, Ronci, Aceto, Ricci, Cipollini, Dell’Anno, De Simone, De Marco, Ferrarini, Beghelli, Mazzoni, Lucacchini, Gemignani, Giusti and Landi.)

Objectives: This study aims to determine whether the sequencing of DNA extracted from pleural fluids (PFs) of Pleural Mesothelioma (PM) patients accurately represents the genetic information obtained from the solid tissue counterpart biopsies with particular attention to the identification of single nucleotide variants (SNVs)., Materials and Methods: Single pleural biopsy, PFs, and blood were collected from PM patients. DNA was extracted from these samples and then subjected to Whole-Exome Sequencing., Results: A higher number of SNVs was identified in PFs than in solid tissue biopsies (STBs). Most SNVs were detected in PFs samples but not in STBs samples, while only a few SNVs were detected in STBs samples but not in PFs samples., Conclusion: The current findings support the notion that PFs might offer a more robust depiction of cancer's molecular diversity. Nonetheless, the current outcomes challenge the assertion that liquid biopsies can encompass the entirety of intra-patient variations. Indeed, a subset of potential cancer-driver SNVs was exclusively identified in STBs. However, relying solely on STBs would have precluded the detection of significant SNVs that were exclusively present in PFs. This implies that while PFs serve as a valuable complement to STBs, they do not supplant them., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

This study described 17 cases of children admitted to the Bambino Gesù Children's Hospital with acute hepatitis of unknown origin between mid-April and November 2022. Following the World Health Organization's working case definition of probable cases, 17 children, with a median age of 2.1 years (interquartile range: 1.0-7.1), presenting with acute hepatitis non-AE, with serum transaminase >500 IU/L, were included in the study. A pre-specified set of microbiological tests was performed on different biological specimens for all pediatric patients. All patients resulted negative for the common hepatotropic viruses. The most common pathogen detected in blood specimens was human-herpes-virus-7 (52.9%). Adenovirus was detected more frequently in stool specimens (62.5%) than in respiratory (20.0%) or blood samples (17.6%). Regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, one child tested positive two days after admission, while antibodies against spike and nucleoprotein were present in 82.3% of patients. A co-pathogen detection was observed in 94.1% of children. Overall, 16 children recovered without clinical complications, while one patient required liver transplantation. In these cases of acute hepatitis of unknown origin, adenovirus was mainly detected in stool samples. A co-pathogen detection was also frequently observed, suggesting that the etiology of this acute hepatitis is most probably multifactorial.

Background and study aims Musculoskeletal disorders (MSDs) and injuries (MSIs) are frequent in gastrointestinal endoscopy. The aim of this study was to assess potential ergonomic advantages of a lighter single-use duodenoscope compared with a standard reusable one for endoscopists performing endoscopic retrograde cholangiopancreatography (ERCP). Methods Three experienced endoscopists performed an ergonomic, preclinical, comparative protocol-guided simulation study of a single-use and a standard reusable duodenoscope using an anatomic bench model. Surface EMG signals from left forearm and arm muscles were recorded. A commercial inertial sensor-based motion capture system was applied to record body posture as well. Results A significant lowering of root mean square amplitude and amplitude distribution of biceps brachii signal (ranging from 13% to 42%) was recorded in all the participants when using a single-use duodenoscope compared with a reusable one. An overall reduction of muscle activation amplitude and duration was also associated with the single-use duodenoscope for forearm muscles, with different behaviors among subjects. Participants spent most of the time in wrist extension (> 80%) and ulnar deviation (> 65%). A consistent pattern of functional range of motion employed for completing all procedures was observed. Conclusions Our study showed that a lighter scope has a promising effect in reducing upper arm muscle activity during ERCP with potential benefit on musculoskeletal health in the ERCP setting., Competing Interests: Conflict of Interest Vincenzo Cennamo: Olympus Italia, Olympus Europa, Euromedical, Novità Medicali. Other authors have any conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Spasticity is a serious complication of spinal cord injury/disease (SCI/D) that affects 60%-80% of patients with this condition. The presence of spasticity can have a significant impact on the outcomes of reconstructive surgical interventions, such as those on pressure sores (PSs). Moreover, in the conservative treatment of PSs, spasticity may prevent maintaining adequate postures to avoid skin friction or traction. The aim of this study is to describe the PS reconstruction outcomes in a cohort of patients with SCI/D affected by spasticity., Methods: In this retrospective study of patients with SCI/D consecutively admitted to Montecatone Rehabilitation Institute between October 2013 and March 2022, 54 PSs were treated in 46 people with spasticity., Results: Postsurgery complications occurred in 26 of 54 treated PS, of which seven were major. Eleven patients experienced more than one complication. The overall incidence of postsurgical complications was 48.1%, and the incidence of major complications was 13%. Median length of hospital stay was 3.8 versus 1.8 months. Compared with other reports in the literature of PS reconstruction in patients with SCI/D, we found higher rates of overall, minor, and major complications., Conclusions: Spasticity proved to be an important condition to consider, and its treatment requires specialized physicians. The collaboration between plastic surgeons and spasticity specialists is crucial to define the best treatment to reduce postoperative complications., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10 -8 ), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10 -7 ), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10 -6 ) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10 -5 ). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk., (© 2024. The Author(s).)

The use of CRISPR/Cas9 system has rapidly grown in the last years. Here, the optimization of gene editing of a single-nucleotide polymorphism in a human non-malignant somatic cell line of thyrocytes (Nthy-Ori) was described highlighting strategies for overcoming the problems concerning the delivery and off-targets. We employed both lentivirus and chemical lipids as delivery agents and two strategies for creating the double-strand breaks (DSB). The former induced a DSB by a classical Cas9 nuclease (standard strategy), while the second one employed a modified Cas9 creating a single-strand break (SSB). The knock-in was carried out using a single-stranded donor oligonucleotide or the HR410-PA donor vector (HR). The desired cells could be obtained by combining the double nickase system with the HR vector transfected chemically. This result could be due to the type of DSB, likely processed mainly by non-homologous end joining when blunt (standard strategy) and by HR when overhanging (double nickase). Our results showed that the double nickase is suitable for knocking-in the immortalized Nthy-Ori cell line, while the standard CRISPR/Cas9 system is suitable for gene knock-out creating in/del mutations., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03878-4., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2024.)

Background: Promoting safe and efficient transitions of care is critical to reducing readmission rates and associated costs and improving the quality of patient care. A growing body of literature suggests that transitional care (TC) programs are effective in improving quality of life and reducing unplanned readmissions for several patient groups. TC programs are highly complex and multidimensional, requiring evidence on how specific practices and system characteristics influence their effectiveness in patient care, readmission reduction and costs., Methods: Using a systematic review and a configurational approach, the study examines the role played by system characteristics (size, ownership, professional skills, technology used), the organizational components implemented, analyzing their combinations, and the potential economic impact of TC programs., Results: The more organizational components are implemented, the greater the likelihood that a TC program will be successful in reducing readmission rates. Not all components have the same effect. The results show that certain components, 'post-discharge symptom monitoring and management' and 'discharge planning', are necessary but not sufficient to achieve the outcome. The results indicate the existence of two different combinations of components that can be considered sufficient for the reduction of readmissions. Furthermore, while system characteristics are underexplored, the study shows different ways of incorporating the skill mix of professionals and their mode of coordination in TC programs. Four organizational models emerge: the health-based monocentric, the social-based monocentric, the multidisciplinary team and the mono-specialist team. The economic impact of the programs is generally positive. Despite an increase in patient management costs, there is an overall reduction in all post-intervention costs, particularly those related to readmissions., Conclusions: The results underline the importance of examining in depth the role of system characteristics and organizational factors in facilitating the creation of a successful TC program. The work gives preliminary insights into how to systematize organizational practices and different coordination modes for facilitating decision-makers' choices in TC implementation. While there is evidence that TC programs also have economic benefits, the quality of economic evaluations is relatively low and needs further study., (© 2024. The Author(s).)

Human disease modeling has been profoundly transformed by the introduction of human induced pluripotent stem cells (iPSCs), marking the onset of a new era. This ground-breaking development offers a tailored framework for generating pluripotent cells from any individual, effectively enabling the development of cellular models for the study of human physiology and diseases on an unprecedented scale. Although technologies for iPSCs generation have advanced rapidly over the past two decades, protocols for reprogramming patient-derived somatic cells into stem cells still pose a major challenge for the development of automated pipelines capable of generating iPSCs at scales that are cost-effective, reproducible, and easy to implement. Most methods commonly rely on extracellular matrix protein mixtures or synthetic substrates to promote efficient proliferation of iPSCs. Nonetheless, employing these substances entails a laborious and time-consuming process, as the culture surface requires coating treatments before cell seeding. Here we describe a method for reprogramming blood-derived mononucleated cells that eliminates the need to precoat culture surfaces for the entire experimental flow. This procedure is suitable for fresh or frozen purified peripheral blood mononuclear cells (PBMCs) and allows seeding of reprogrammed cells in a culture medium containing a fragment of laminin-511, regardless of the method of reprogramming employed. Our protocol incorporates a streamlined workflow that optimizes key factors, including cell density, culture medium composition, and iPSC culture propagation techniques. Using a precoating-free approach, we eliminate the time-consuming steps, while our optimized subcloning method improves the scalability of the protocol, making it suitable for large-scale applications. Additionally, the automation-friendly nature of our protocol allows for high-throughput processing, reducing the labor and costs associated with manual handling. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Miniaturized and time efficient precoating-free reprogramming of fresh or frozen PBMCs Alternate Protocol: Erythroid progenitor cells (EPCs) enrichment and reprogramming into iPSCs using Sendai viral vectors Basic Protocol 2: Picking and precoating-free optimized expansion of iPSC clones., (© 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Pressure injuries (PIs) are a common complication in patients with spinal cord injury/disorder (SCI/D), and deep PIs require surgical treatment consisting of wide debridement and adequate reconstruction. We conducted a retrospective observational study at a tertiary rehabilitation hospital for SCI/D in Italy with the aim of describing the incidence and associated risk factors of postoperative complications in individuals with SCI/D presenting with chronic deep PIs, treated with a specific flap selection algorithm based on the site of the defect, the presence of scars from previous surgeries, and the need to spare reconstructive options for possible future recurrences. Medical records of surgical procedures performed on SCI/D patients with fourth-degree PIs, according to NPUAP classification (National Pressure Ulcer Advisory Panel), between July 2011 and January 2018 were reviewed. A total of 434 surgical procedures for fourth-degree PIs in 375 SCI/D patients were analyzed. After a mean follow-up of 21 months (range 12-36), 59 PIs (13.6%) had minor complications, and 17 (3.9%) had major complications requiring reoperation. The sacral site and muscular and musculocutaneous flaps were significant risk factors for postoperative complications. Six patients (1.4%) had a recurrence. The choice of flap correlates with the outcome of decubitus reconstruction. Therefore, reconstructive planning should be based on established principles.

Despite the theoretical high productivity, microalgae-based oil production is not economically sustainable due to the high cost of photoautotrophic cultures. Heterotrophic growth is a suitable economic alternative to overcoming light dependence and climatic/geographic fluctuations. Here we report data about growth performance, biomass production, and lipid composition of the marine diatom Cyclotella cryptica , chosen as a model strain for biodiesel production in heterothrophy. A repeated-batch process of heterotrophic cultivation has also been investigated to assess the robustness and phenotypic stability. The process consisting of six constant cycle repetitions was carried out for 42 days and led to an average dry biomass production of 1.5 ± 0.1 g L -1 of which 20% lipids composed of 60% triglycerides, 20% phospholipids. and 20% glycolipids. The major fatty acids were C16:0 (∼26%), C16:1 ω-7 (∼57%), and C20:5 ω-3 (∼12%), with a significant reduction in the unsaturated fatty acids in comparison to other microalgae grown in heterotrophy. Fatty acids were differently distributed among the glycerolipid classes, and the lipid composition was used to compare the potential properties of C. cryptica oil with traditional vegetable biofuels., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride homeostasis is ideally placed to regulate activity. We therefore investigated the stability of baseline [Cl - ] i in adult mouse neocortex, using in vivo two-photon imaging. We found a two-fold increase in baseline [Cl - ] i in layer 2/3 pyramidal neurons, from day to night, with marked effects upon both physiological cortical processing and seizure susceptibility. Importantly, the night-time activity can be converted to the day-time pattern by local inhibition of NKCC1, while inhibition of KCC2 converts day-time [Cl - ] i towards night-time levels. Changes in the surface expression and phosphorylation of the cation-chloride cotransporters, NKCC1 and KCC2, matched these pharmacological effects. When we extended the dark period by 4 h, mice remained active, but [Cl - ] i was modulated as for animals in normal light cycles. Our data thus demonstrate a daily [Cl - ] i modulation with complex effects on cortical excitability., (© 2023. The Author(s).)

In recent years, plastic pollution has become a growing environmental concern: more than 350 million tons of plastic material are produced annually. Although many efforts have been made to recycle waste, a significant proportion of these plastics contaminate and accumulate in the environment. A central point in plastic pollution is demonstrated by the evidence that plastic objects gradually and continuously split up into smaller pieces, thus producing subtle and invisible pollution caused by microplastics (MP) and nanoplastics (NP). The small dimensions of these particles allow for the diffusion of these contaminants in farmlands, forest, freshwater, and oceans worldwide, posing serious menaces to human, animal, and plant health. The uptake of MPs and NPs into plant cells seriously affects plant growth, development, and photosynthesis, finally limiting crop yields and endangering natural environmental biodiversity. Furthermore, nano- and microplastics-once adsorbed by plants-can easily enter the food chain, being highly toxic to animals and humans. This review addresses the impacts of MP and NP particles on plants in the terrestrial environment. In particular, we provide an overview here of the detrimental effects of photosynthetic injuries, oxidative stress, ROS production, and protein damage triggered by MN and NP in higher plants and, more specifically, in crops. The possible damage at the physiological and environmental levels is discussed.

Introduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate., Materials and Methods: We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase., Results: The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93×10 -8 in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a 'C-phosphate-G' (CpG) site located in the promoter region of the RCCD1 antisense ( RCCD1-AS1 ) gene which, when expressed, decreases the expression of the RCC1 domain-containing ( RCCD1 ) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of RCCD1 gene expression, made possible by the inactivity of RCCD1-AS1 ., Conclusion: We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC., Methods: A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed., Results: Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69-5.04, P = 1.44 × 10 -4 ). For diabetes, the corresponding OR was 14.95 (95% CI 3.41-65.50, P = 3.58 × 10 -4 )., Conclusion: In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC., Competing Interests: Conflict of interest M.F.B. has received research funding from Celgene and Lead Pharma and acted as a consultant to Servier. H.W.M.L. reports research funding and/or medication supply from Bristol-Myers Squibb, Bayer Schering Pharma, Celgene, Janssen-Cilag, Lilly, Nordic Pharma, Philips Healthcare, Roche, Merck Sharp and Dohme, Servier, Incyte; and consultant/advisory board member for Lilly, Nordic Pharma, Bristol-Myers Squibb, Dragonfly, Merck Sharp and Dohme, Servier, all outside the submitted work. The other authors do not have any conflict of interest to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aims: Nfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members (Nfia, b, c, x). Nfix plays important roles in the development and function of several organs. In muscle development, Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow-twitching fibres. Nfix is expressed also in the heart, but its function has been never investigated before. We studied Nfix role in this organ., Methods: Using Nfix-null and wild type (WT) mice we analyzed: (1) the expression pattern of Nfix during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis., Results and Conclusions: Nfix expression start in the heart from E12.5. Adult hearts of Nfix-null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix-null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix-null mice express a significantly larger L-type calcium current (Cacna1d + Cacna1c). Interestingly, downregulation of Nfix by sh-RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in I CaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L-type calcium current, modulates heart rate., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

This research presents a dual-pronged bibliometric and systematic review of the integration of phase change materials (PCM) in asphalt pavements to counteract the urban heat island (UHI) effect. The bibliometric approach discerns the evolution of PCM-inclusion asphalt research, highlighting a marked rise in the number of publications between 2019 and 2022. Notably, Chang'an University in China has emerged as a leading contributor. The systematic review addresses key questions like optimal PCM types for UHI effect mitigation, strategies for PCM leakage prevention in asphalt, and effects on mechanical properties. The findings identify polyethylene glycols (PEGs), especially PEG2000 and PEG4000, as prevailing PCM due to their wide phase-change temperature range and significant enthalpy during phase transitions. While including PCM can modify asphalt's mechanical attributes, such mixtures typically stay within performance norms. This review emphasises the potential of PCM in urban heat management and the need for further research to achieve optimal thermal and mechanical balance., Competing Interests: The authors declare no conflict of interest.

Background: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations., Results: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10 -6 ), with a P-value close to a threshold that takes into account multiple testing., Conclusions: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk., (© 2023. Sociedad de Biologia de Chile.)