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Subcellular compartmentalization of metabolic enzymes establishes a unique metabolic environment that elicits specific cellular functions. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we show that the nuclear localization of the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces severe methylation defects and impedes correct mitosis completion. MTHFD2 deficient cells display chromosome congression and segregation defects and accumulate chromosomal aberrations. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, whereas restricting MTHFD2 to the nucleus is sufficient to ensure correct mitotic progression. Our discovery uncovers a nuclear role for MTHFD2, supporting the notion that translocation of metabolic enzymes to the nucleus is required to meet precise chromatin needs. The nuclear localization of metabolic enzymes is fascinating and in most cases remains a mystery. Here, Pardo Lorente and colleagues show that nuclear MTHFD2 is required for successful mitosis by controlling centromeric histone methylation. [ABSTRACT FROM AUTHOR]

It has been shown recently, without an explanation of the possible molecular mechanisms involved, that 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic (EPPS) acid effectively protects from the neurotoxicity induced by oligomers and plaques formed by the protein amyloid-β protein. Here we report the same protective effect, obtained in vitro (HT22-diff cell line) and ex vivo (hippocampal slices) models, against amyloid neurotoxicity induced by oligomers of salmon Calcitonin (sCT), which has been shown to be a good model for the study of neurodegenerative diseases. Based on biophysical studies focusing on the protein aggregation kinetic and the interaction of the aggregates with model membranes, we propose a possible molecular mechanism underlying the protective effects. Taken together, our results indicate that EPPS is able to counteract the direct association (primary aggregation) of harmless low-molecular weight aggregates (dimers and trimers) or their aggregation catalysed by surfaces present in the solution (secondary aggregation). Thus, EPPS stabilizes harmless aggregates and hinders the formation of toxic and metastable prefibrillar oligomers. Overall, our data demonstrate that EPPS is an excellent drug candidate for the treatment of neurodegeneration due to misfolded proteins, such as Alzheimer's or Parkinson's disease. [ABSTRACT FROM AUTHOR]

The performance of density functional theory (DFT)-based calculations combined with different basis set was evaluated on potential iron (II) photosensitizer. BP86-D3(BJ), PBE-D3(BJ), TPSS-D3(BJ), OPBE-D3(BJ), B3LYP-D3(BJ), PBE0-D3(BJ) and TPSSh-D3(BJ) functionals were assessed against X-ray data and the PBE, B3LYP, O3LYP, PBE0, CAM-B3LYP and ωB97X functionals for UV–Vis absorption spectrum. For obtaining the geometries, PBE is a good choice, regardless the basis set size, while OPBE does well only when larger basis set are employed. Regarding the excited states energies, the referred protocol III, E EE , gas TD - DFT R solv GS - E GS , gas R solv GS , was found to meet the "Pauling Point" criteria, a situation wherein the cancelation of significant errors yields a physically balanced model, allowing an affordable and reliable way to understand their excited state's electronic structure. Specifically, TD-DFT calculations using def2-TZVP basis set combined with B3LYP or CAM-B3LYP functionals can be recommended to treat the excited states of the explored iron (II) complex. The study additionally looks at the molecular and electronic structures of a series of similar complexes, collecting understanding to help tune their properties and of related systems as photosensitizers. [ABSTRACT FROM AUTHOR]

Background: Southeast Asian (SEA) mangroves are globally recognized as blue carbon hotspots. Methodologies that measure mangrove soil carbon stock (SCS) are either accurate but costly (i.e., elemental analyzers), or economical but less accurate (i.e., loss-on-ignition [LOI]). Most SEA countries estimate SCS by measuring soil organic matter (OM) through the LOI method then converting it into organic carbon (OC) using a conventional conversion equation (%Corg = 0.415 * % LOI + 2.89, R2 = 0.59, n = 78) developed from Palau mangroves. The local site conditions in Palau does not reflect the wide range of environmental settings and disturbances in the Philippines. Consequently, the conventional conversion equation possibly compounds the inaccuracies of converting OM to OC causing over- or under-estimated SCS. Here, we generated a localized OM-OC conversion equation and tested its accuracy in computing SCS against the conventional equation. The localized equation was generated by plotting % OC (from elemental analyzer) against the % OM (from LOI). The study was conducted in different mangrove stands (natural, restored, and mangrove-recolonized fishponds) in Oriental Mindoro and Sorsogon, Philippines from the West and North Philippine Sea biogeographic regions, respectively. The OM:OC ratios were also statistically tested based on (a) stand types, (b) among natural stands, and (c) across different ages of the restored and recolonized stands. Increasing the accuracy of OM-OC conversion equations will improve SCS estimates that will yield reasonable C emission reduction targets for the country's commitments on Nationally Determined Contributions (NDC) under the Paris Agreement. Results: The localized conversion equation is %OC = 0.36 * % LOI + 2.40 (R2 = 0.67; n = 458). The SOM:OC ratios showed significant differences based on stand types (x2 = 19.24; P = 6.63 × 10–05), among natural stands (F = 23.22; p = 1.17 × 10–08), and among ages of restored (F = 5.14; P = 0.03) and recolonized stands (F = 3.4; P = 0.02). SCS estimates using the localized (5%) and stand-specific equations (7%) were similar with the values derived from an elemental analyzer. In contrast, the conventional equation overestimates SCS by 20%. Conclusions: The calculated SCS improves as the conversion equation becomes more reflective of localized site conditions. Both localized and stand-specific conversion equations yielded more accurate SCS compared to the conventional equation. While our study explored only two out of the six marine biogeographic regions in the Philippines, we proved that having a localized conversion equation leads to improved SCS measurements. Using our proposed equations will make more realistic SCS targets (and therefore GHG reductions) in designing mangrove restoration programs to achieve the country's NDC commitments. [ABSTRACT FROM AUTHOR]

Introduction: The 2021 European Society of Cardiology (ESC) Guidelines recommend the use of four different classes of drugs for heart failure with reduced ejection fraction (HFrEF): beta blockers (BB), sodium-glucose cotransporter-2 inhibitors (SGLT2i), angiotensin receptor/neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRAs). Moreover, the 2023 ESC updated Guidelines suggest an intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge, based on trials not using the four-pillars. We hypothesized that an early concomitantly administration and up-titration of four-pillars, compared with a conventional stepwise approach, may impact the vulnerable phase after hospitalization owing to HF. Methods: This prospective, single center, observational study included consecutive in-hospital patients with HFrEF. After performing propensity score matching, they were divided according to treatment strategy into group 1 (G1), with predischarge start of all four-pillars, with their up-titration within 1 month, and group 2 (G2) with the pre Guidelines update stepwise four-pillars introduction. HF hospitalization, cardiovascular (CV) death, and the composite of both were evaluated between the two groups at 6-month follow-up. Results: The study included a total of 278 patients who completed 6-month follow-up (139 for both groups). There were no differences in terms of baseline features between the two groups. At survival analysis, HF hospitalization risk was significantly lower in G1 compared with G2 (p < 0.001), while no significant differences were observed regarding CV death (p = 0.642) or the composite of CV death and HF hospitalization (p = 0.135). Conclusions: In our real-world population, patients with HF treated with a predischarge and simultaneous use of four-pillars showed a reduced risk of HF hospitalization during the vulnerable phase after discharge, compared with a conventional stepwise approach. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the substitution of soybean meals by biodiesel co-products on the performance and nutrient balance of lactating cows on pasture. Twelve dairy cows (7/8 Holstein-Gir) in early lactation were included in this feeding trial. These animals had an average daily milk yield of 21.1 kg and were distributed in a 4 × 4 triple Latin square experimental design. Protein supplements fed to these lactating cows contained peanut meal, cotton and sunflower as a complete replacement for soybean meal. Nutrient intake and digestibility, milk production, microbial protein synthesis, energy and protein balance were the parameters assessed in this study. Supplements containing different biodiesel co-products did not influence (P > 0.05) the level of forage intake, supplementation and nutrient by lactating cows, except for the total digestible nutrients (TDN) intake which was higher (P ≤ 0.05) in cows supplemented with cottonseed meal. The cotton meal also promoted higher digestibility of TDN (P = 0.001) and total carbohydrates (TCHO; P = 0.001) of the diet and, as a result, higher energy consumption (P = 0.01) and lower negative energy balance (P = 0.01). Cottonseed meal is a co-product of the biodiesel industry that has the ability to replace soybean meal as a source of protein in the supplement without affecting performance and promoting greater energy availability, demonstrating its ability to reduce the effects of negative energy balance in cows at the beginning of lactation kept on tropical pastures. [ABSTRACT FROM AUTHOR]

Brazil boasts one of the world's richest biodiversities, including untapped sources of native species. Psidium cattleyanum Sabine is one of many underutilized species with potential for commercial exploitation, offering economic and health benefits. Considering this potential and the limited information on the species' genetic structures, this study aims to evaluate genetic divergence using physicochemical and morphometric characters of 16 accessions of this species. For this purpose, a germplasm collection containing P. cattleyanum from the Agronomic Institute of Pernambuco (IPA) in Brazil was evaluated. The fruits were collected and sent to the Forest Seed Analysis Laboratory (LASF) at the Federal Rural University of Pernambuco (UFRPE) for characterization. Germplasm characterization included an analysis of physicochemical and morphometric fruit characteristics. Subsequent analyses included genetic correlation between traits, genetic parameters, principal component analysis, and the Mulamba and Mock selection index for the accessions. The analysis of genetic divergence enabled identifying valuable P. cattleyanum accessions for future breeding programs, considering genetic variability based on morphological fruit characteristics. Furthermore, selection based on the Mulamba and Mock index highlighted high-performing individuals (A1.30, A1.40, A1.48, A1.44 and A1.21), enabling choices based on various characteristics for potential genotypic gains. This demonstrates the importance of a comprehensive approach in selecting accessions for species improvement. [ABSTRACT FROM AUTHOR]

Graphene is a two-dimensional carbon material with unique properties, such as high thermal and electrical conductivity, mechanical strength, elasticity, and biocompatibility. The methods used to synthesize graphene affect its structural properties, including flaws, layer count, crystalline domain size, and impurities, ultimately affecting the properties and performance of graphene-based materials. This review aims to analyze the methods used to characterize graphene, using both ISO/IEC standards and current literature as references. The discussed techniques are diverse, yet complementary, and include ultraviolet–visible spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray absorption near edge structure, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, the Brunauer–Emmett–Teller method, thermogravimetric analysis, in-line four-point probe, resonant cavity and terahertz time-domain spectroscopy, besides an alternative method to determine the graphene domain. By employing rigorous characterization techniques, researchers and industry professionals can ensure the reliability, effectiveness, and trustworthiness of graphene-based materials for various applications. [ABSTRACT FROM AUTHOR]

Polyvinylidene fluoride (PVDF) boosted its technological applications because of its piezoelectric and pyroelectric properties, together with mechanical, chemical, and thermal resistance. In this review, we address the PVDF chemical structure and its synthesis procedure, also describing the occurrence of polymorphism (alpha (α), beta (β), gamma (γ), and delta (δ) of this semicrystalline polymer, and the processes involved in phase transformation that govern the adaptability of the PVDF crystalline phases and properties for several industrial uses. It can be used as a component of implants and sutures, as engineering plastic to play a structural role in aggressive environments, acting in the field of process control as a component of transducers and sensors, as well as in the synthesis of separation membranes, fuel cells, and a long list of new applications that include an important role in robotics. The main physicochemical techniques used for PVDF characterization, i.e., differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy, that highlight its unique properties, are also discussed, showing the versatility of PVDF for a range of biomedical and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

As artificial intelligence (AI) becomes widespread, there is increasing attention on investigating bias in machine learning (ML) models. Previous research concentrated on classification problems, with little emphasis on regression models. This paper presents an easy-to-apply and effective methodology for mitigating bias in bagging and boosting regression models, that is also applicable to any model trained through minimizing a differentiable loss function. Our methodology measures bias rigorously and extends the ML model's loss function with a regularization term to penalize high correlations between model errors and protected attributes. We applied our approach to three popular tree-based ensemble models: a random forest model (RF), a gradient-boosted model (GBT), and an extreme gradient boosting model (XGBoost). We implemented our methodology on a case study for predicting road-level traffic volume, where RF, GBT, and XGBoost models were shown to have high accuracy. Despite high accuracy, the ML models were shown to perform poorly on roads in minority-populated areas. Our bias mitigation approach reduced minority-related bias by over 50%. [ABSTRACT FROM AUTHOR]

Purpose: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. Methods: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. Results: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. Conclusion: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20–30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. Methods: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. Results: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). Conclusions: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition. [ABSTRACT FROM AUTHOR]

We show that attosecond core-level spectroscopy is a powerful tool for investigating molecular dynamics due to its combined attosecond temporal resolution and the broad coherent spectrum that allows deciphering the signatures of nuclear and electronic motion through their different energetic signatures. The method reveals that the correlated real-time electronic and nuclear wavepacket dynamics and non-adiabatic transitions across conical intersections identify electronic and nuclear coherences and directly register symmetry changes in the X-ray absorption spectrum. We demonstrate the method's efficacy to unveil the entire time history of the ring-opening dynamics of furan. The investigation establishes attosecond core-level spectroscopy as a potent method to investigate the real-time dynamics of photochemical reaction pathways in molecular systems. Attosecond core-level spectroscopy is used to probe the ultrafast molecular dynamics of furan at the carbon K-edge, demonstrating its ability to simultaneously probe electronic and vibrational dynamics. [ABSTRACT FROM AUTHOR]

Background: The optimal timing and surgical approach for surgical revascularization in patients with moyamoya syndrome (MMS) associated with neurofibromatosis type I (NF1) remain so far elusive. We aimed to compare the long-term clinical, radiological, and cognitive effects of different revascularization procedures in a pediatric cohort of NF1-associated MMS. Methods: We reviewed the clinical, radiological, and surgical data of 26 patients with NF1-associated MMS diagnosed at our institution between 2012 and 2022, at the clinical onset and last follow-up. Results: Indirect bypasses were performed in 12/26 patients (57.1%), while combined direct and indirect procedures in 9/26 subjects (42.9%); 5 patients did not undergo surgery. Through logistic regression analysis, pathological Wechsler Intelligence Scale for Children (WISC) at onset was found to be associated with symptom improvement at 1-year follow up (p = 0.006). No significant differences were found in long-term neurocognitive outcome and stroke rate in patients receiving combined or indirect bypass (p > 0.05). Conclusions: Currently, whether combined or indirect bypass should be considered the treatment of choice in pediatric patients with NF1-associated MMS remains unclear, as well as the optimal time approach. In our series, no significant differences were found in long-term neurocognitive outcome and stroke rate between patients treated with either of these two approaches. Clinical evidence supports the crucial role of early diagnosis and surgical revascularization in subjects with MMS-associated NF1, even in case of mildly symptomatic vasculopathy. This allows to achieve a good long-term outcome with improved intellectual function and prevention of stroke and seizure in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To validate a semiautomated method for segmenting vein of Galen aneurysmal malformations (VGAM) and to assess the relationship between VGAM volume and other angioarchitectural features, cardiological findings, and outcomes. Methods: In this retrospective study, we selected all subjects with VGAM admitted to the Gaslini Children's Hospital between 2009 and 2022. Clinical data were retrieved from electronic charts. We compared 3D-Slicer segmented VGAM volumes obtained by two independent observers using phase-contrast MR venography to those obtained with manual measurements performed on T2-weighted images. The relationship between VGAM volumes and clinical and neuroimaging features was then explored. Results: Forty-three subjects with VGAM (22 males, mean age 6.56 days) were included in the study. Manual and semiautomated VGAM volumes were well correlated for both readers (r = 0.86 and 0.82, respectively). Regarding reproducibility, the inter-rater interclass correlation coefficients were 0.885 for the manual method and 0.992 for the semiautomated method (p < 0.001). The standard error for repeated measures was lower for the semiautomated method (0.04 versus 0.40 of manual method). Higher VGAM volume was associated with superior sagittal sinus narrowing, jugular bulb stenosis, and aqueductal stenosis (p < 0.05). A weak correlation was found between VGAM volume and straight sinus dilatation (r = 0.331) and superior sagittal sinus index (r = − 0.325). No significant associations were found with cardiac findings, post-embolization complications, and outcome (p > 0.05). Conclusions: Semiautomated VGAM volumetry is feasible and reliable with improved reproducibility compared to the manual method. VGAM volume is not a prognostic factor for clinical outcome, but it is related to other venous findings with potential hemodynamic effects. [ABSTRACT FROM AUTHOR]

We analyze the problem of constructing multiple buy-and-hold mean-variance portfolios over increasing investment horizons in continuous-time arbitrage-free stochastic interest rate markets. The orthogonal approach to the one-period mean-variance optimization of Hansen and Richard (Econometrica 55(3):587–613, 1987) requires the replication of a risky payoff for each investment horizon. When many maturities are considered, a large number of payoffs must be replicated, with an impact on transaction costs. In this paper, we orthogonally decompose the whole processes defined by asset returns to obtain a mean-variance frontier generated by the same two securities across a multiplicity of horizons. Our risk-adjusted mean-variance frontier rests on the martingale property of the returns discounted by the log-optimal portfolio and features a horizon consistency property. The outcome is that the replication of a single risky payoff is required to implement such frontier at any investment horizon. As a result, when transaction costs are taken into account, our risk-adjusted mean-variance frontier may outperform the traditional mean-variance optimal strategies in terms of Sharpe ratio. Realistic numerical examples show the improvements of our approach in medium- or long-term cashflow management, when a sequence of target returns at increasing investment horizons is considered. [ABSTRACT FROM AUTHOR]

This study proposes a novel approach to improve the performance of third-generation solar cells, particularly perovskite solar cells (PSCs), by employing zinc oxide (ZnO) nanoparticles (NPs). The ZnO NPs are dispersed on the upper surface of the device, acting as nanodiffusers. This reduces reflection and increases solar radiation absorption in the photovoltaic active layer, enhancing the light pathway within the device. To analyze the impact of ZnO nanodiffusers on solar cell performance, computer simulations using the finite element method (FEM) and experimental analysis were conducted. Green synthesis methods were employed to synthesize ZnO nanoparticles with an average size of 160 nm, which were subsequently characterized. Thin films of ZnO NPs were deposited on the transparent indium tin oxide (ITO) electrode using spin coating, and their optical response was evaluated. This study proposes methodologies for optical and electrical modeling of third-generation photovoltaic cells using ZnO NPs. Optical computational modeling results evidence that ZnO nanospheres with a diameter of 160 nm predominantly scatter solar radiation in the forward direction. The incorporation of ZnO NPs (160 nm in diameter) reduces device reflectance, resulting in efficient light coupling and increased absorbance in the active layer. The integrated effects of light trapping and anti-reflective properties enhance photocurrent generation, leading to an increase in short-circuit current density. Experimental verification with ZnO NP deposition on PSCs confirms a 23.5% enhancement in photovoltaic device efficiency, increasing from 10.6 to 13.1% in an 11.68 cm2 perovskite cell. The study presents the optical benefits of ZnO nanostructures, including anti-reflective effects and light scattering, when integrated into devices containing thin films as active material. [ABSTRACT FROM AUTHOR]

Two new dactylogyrid species were found infecting the gill filaments of two freshwater fishes collected in the Amazon River basin around Madre de Dios, Peru, namely, Demidospermus wilverin. sp. from Loricaria sp. (Siluriformes: Loricariidae), and Notozothecium agustin. sp. from Brycon amazonicus (Spix & Agassiz) (Characiformes: Bryconidae). Demidospermus wilverin. sp. is characterized by having the following combination of characteristics: (1) a male copulatory organ (MCO) with 1½ rings and a spoon-shaped distal end, (2) an accessory piece with expanded distal end, (3) dorsal and ventral bars with broadly V-shaped and expanded ends, and (4) hooks similar in size. Notozothecium agustin. sp. differs from its ten congeners by the following combination of characteristics: (1) a coiled MCO with 1½ rings and a sinuous accessory piece with kidney-shaped distal end, (2) an rod-shaped and straight dorsal bar, (3) and anchors with robust superficial roots. Demidospermus wilverin. sp. represents the thirty-second species in the genus, the eighth from Peru and the fifth parasitising a loricariid catfish from the Peruvian Amazon. Notozothecium agustin. sp. is the second species of the genus described in Peru and the first species infecting a bryconid host. [ABSTRACT FROM AUTHOR]

As social robots are being built with the aim of employing them in our social environments, it is crucial to understand whether we are inclined to include them in our social ingroups. Social inclusion might depend on various factors. To understand if people have the tendency to treat robots as their in-group members, we adapted a classical social psychology paradigm, namely the "Cyberball game", to a 3-D experimental protocol involving an embodied humanoid robot. In our experiment, participants played the ball-tossing game with the iCub robot and another human confederate. In our version, the human confederate was instructed to exclude the robot from the game. This was done to investigate whether participants would re-include the robot in the game. In addition, we examined if acquired technical knowledge about robots would affect social inclusion. To this aim, participants performed the Cyberball twice, namely before and after a familiarization phase when they were provided with technical knowledge about the mechanics and software related to the functionality of the robot. Results showed that participants socially re-included the robot during the task, equally before and after the familiarization session. The familiarization phase did not affect the frequency of social inclusion, suggesting that humans tend to socially include robots, independent of the knowledge they have about their inner functioning. [ABSTRACT FROM AUTHOR]

Background: The persistently patent ductus arteriosus represents a well-known common congenital heart defect; it is uncommon in adult patients, and in any case, it debuts with atrial fibrillation. Case presentation: A 75-year-old woman suffering from persistent ductus arteriosus (PDA) was admitted to the cardiology department because of atrial fibrillation, dyspnea and exercise intolerance. A PDA was detected on echocardiography and globally assessed through ECG-gated CT angiography. Conclusions: Patent ductus arteriosus is an uncommon clinical finding in adulthood, and atrial fibrillation, as a consequence of chronic, progressive left atrial enlargement, may be the initial symptom. We describe the ECG-gated CT angiography imaging features of unknown patent ductus arteriosus in an elderly patient who debuted with atrial fibrillation. [ABSTRACT FROM AUTHOR]

The aim of this study was to produce an alcohol gel hand sanitizer containing green glycerol. Crude glycerol was purified using chemical and physical treatments. The sanitizer was prepared using 71.100 g of 99.3° GL ethanol, 28.0 g H2O, 0.5 g of Carboxypolymethylene [Carbopol 940® or Carbomer], 5 drops of triethanolamine (pH 5–7), and glycerol (1.5% w/w). The thermal behavior of the ethanol, carbopol, triethanolamine, glycerol, and alcohol gels were evaluated using Thermogravimetry and Differential Thermal Analysis. The apparent viscosity was obtained using a rotary viscometer. The determination of in vitro spreadability was achieved by an adaptation of the Knorst method. The ethanol content was measured by headspace gas chromatography using a flame ionization detector. The thermal behavior of the gels was influenced by the presence of glycerol, which confirms the possible network interactions formed. The relative densities of the samples were between 0.887 and 0.890 g/cm3. No alteration of the pH of the formulation resulted from the incorporation of glycerol. The apparent viscosities of the alcohol gels were greater than 20,000 cP. No alteration in the in vitro spreadability of the gel alcohol (530.6 mm2) resulted from the addition of glycerol. Hand sanitizer was produced using glycerol from a transesterification reaction. It represents an alternative use for the glycerol being produced in biodiesel processes. The product satisfied the requirements of WHO that preconize a formulation containing 1.45% glycerol as an humectant to protect skin against dryness and dermatitis. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood–brain barrier disruption in MS lesions. Clinical relevance statement: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. Key Points: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice. [ABSTRACT FROM AUTHOR]

In this work, we present a study on the resistive memory properties of ITO/MEH-PPV/Al devices. The pristine diode-like device, highly resistive, needs an electroforming process to turn the device into a memory with resistive switching. During electroforming, I-V sweeps are described using Schottky Emission (SE) and Fowler-Nordheim (FN) models, resulting in an injection barrier around ~ 0.8 to 0.9 eV that may be associated with injection through polymer/Al interface. At high resistance sate (HRS), the linear coefficient of the log I x V curve is n ≅ 1 at low voltages and present a transition to n ≅ 2 when the device is close to switching voltage. At low resistance state (LRS), we observe n ≅ 1 up to the negative differential resistance (NDR). In our devices, exploring the reverse bias NDR at different levels, it is possible to observe multilevel conducting states in direct bias sweeps (opposite polarizations), unlike unipolar memories, that show multilevel states when exploring NDR at different levels in the same polarization direction. I-V multilevel sweeps are in accordance with the Quantum Point Contact Model (QPC). The resulting fitting parameters show that the number of filaments increases from one (at HRS) to 70 as multilevel state approach LRS. Also, the tgap decreases from (0.59 ± 0.02) nm to (0.44 ± 0.01) nm . The conductance found in terms of G 0 ( = 2 e 2 / h = 7.75 x 10 - 5 S ) was 1 G 0 up to 11.5 G 0 , compatible with values found from QPC model on I-V multilevel. Our results are consistent with the soft breakdown of an Al2O3 oxide layer at the polymer/metal interface. [ABSTRACT FROM AUTHOR]

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis. A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis. [ABSTRACT FROM AUTHOR]

The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal. [ABSTRACT FROM AUTHOR]

Evolutionary multi-objective optimization is a field that has experienced a rapid growth in the last two decades. Although an important number of new multi-objective evolutionary algorithms have been designed and implemented by the scientific community, the popular Non-Dominated Sorting Genetic Algorithm (NSGA-II) remains as a widely used baseline for algorithm performance comparison purposes and applied to different engineering problems. Since every evolutionary algorithm needs several parameters to be set up in order to operate, parameter control constitutes a crucial task for obtaining an effective and efficient performance in its execution. However, despite the advancements in parameter control for evolutionary algorithms, NSGA-II has been mainly used in the literature with fine-tuned static parameters. This paper introduces a novel and computationally lightweight self-adaptation mechanism for controlling the distribution index parameter of the polynomial mutation operator usually employed by NSGA-II in particular and by multi-objective evolutionary algorithms in general. Additionally, the classical NSGA-II using polynomial mutation with a static distribution index is compared with this new version utilizing a self-adapted parameter. The experiments carried out over twenty-five benchmark problems show that the proposed modified NSGA-II with a self-adaptive mutator outperforms its static counterpart in more than 75% of the problems using three quality metrics (hypervolume, generalized spread, and modified inverted generational distance). [ABSTRACT FROM AUTHOR]

Spectral characterization of coffee cultivars after pruning may help predict the crop's diverse phytotechnical behaviors. Therefore, this study aimed to differentiate coffee genotypes based on leaf reflectance following pruning and to develop models capable of estimating the agronomic parameters of vegetative growth. This study included eight coffee cultivars. The biochemical and leaf structure parameters were quantified for the spectral characterization of each genotype and adopted as the basis for the application of vegetation indices and to generate models that can estimate agronomic parameters after pruning. The cultivar Topázio MG-1190 proved to be the most efficient at absorbing electromagnetic radiation in the blue (220–510 nm), green (520–590 nm), and red (690–730 nm) spectral ranges among all other cultivars after pruning. The regression models could estimate the following vegetative growth parameters of the coffee cultivars: height using the normalized difference water index (root mean square error (RMSE) = 5.78%), crown diameter and plagiotropic branch length using the enhanced vegetation index (RMSE = 10.21% and 12.69%, respectively), the number of nodes using the chlorophyll b index (RMSE = 14.47%), chlorophyll a content using the photochemical reflectance index (RMSE = 2.39%), and leaf water potential using the leaf water vegetation index-1 (40.72%). The hyperspectral characterization of coffee cultivars with respect to the phytotechnical development of the genotypes after pruning was successfully accomplished. This tool can assist coffee growers to enhance their competitiveness and productivity through the development of management strategies such as the early detection of plant growth issues. [ABSTRACT FROM AUTHOR]

Background: The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze the prevalence of BRAF p.V600E in benign mixed epithelial and mesenchymal and malignant odontogenic tumors. In addition, we discussed the different detection methods used to assess for aberrant BRAF. Methods: This systematic review followed the PRISMA guidelines and was registered in Prospero (CRD42023445689). A comprehensive search of the PubMed/MEDLINE, Scopus, Web of Science, and Embase electronic databases was performed to answer the question "What is the prevalence of the BRAF p.V600E mutation in benign mixed and malignant odontogenic tumors?" The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool. Results: Initially, 387 records were identified, but only 11 articles met the inclusion criteria. A total of 70 patients with benign mixed epithelial and mesenchymal odontogenic tumors and 63 with malignant odontogenic tumors were included in the analysis. We found that the BRAF p.V600E mutation had a prevalence of 31.42% in mixed tumors and 26.98% in malignant odontogenic tumors. Moreover, immunohistochemistry showed high concordance with DNA-based molecular methods. Conclusion: In general, the BRAF p.V600E variant exhibited a prominent prevalence in mixed and malignant odontogenic tumors. However, most of the findings are based on small cohorts of patients and further studies with larger cohorts are needed. [ABSTRACT FROM AUTHOR]

Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young's moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA significantly accelerated wound closure, improved collagenization, increased histological grading, and hastened myofibroblast differentiation in comparison to the control, GelMA, and GEA. GelMA containing AEPG (GPG) improved wound healing, and although gallic acid is the major responsible for such biological activity, a potential synergic effect played by other polyphenols present in the extract is evident. [ABSTRACT FROM AUTHOR]

Pyrolysis has been one of the technologies used to convert biomass into biofuels. Therefore, mathematical models that can represent its phenomena are of fundamental importance in understanding the reaction progression and optimizing the process. In this sense, this study compared the results obtained from the lumped-capacitance thermal model proposed in this work with the thermal discretization model that considers thermal conductivity as a function of temperature. Then, the effect of operational parameters such as temperature, gas velocity, and biomass particle diameter, was compared on the reaction conversion rate. To describe the behavior and interaction between the phases, we utilized an Eulerian-Lagrangian CFD modeling approach, solving the continuity, momentum, energy, species, and turbulence equations using OpenFOAM. A factorial design of the type 2k was used to manipulate the model's input parameters, with biomass conversion as the response variable. The numerical results of biomass conversion from the lumped-capacitance model showed good agreement with the data reported in the literature for the discretized model. However, we observed a difference of 9.13% in the particle mass behavior and 7.63% in the particle residence time. The design of experiments (DoE) enabled us to determine the impact of individual parameters and their interactions on the pyrolysis conversion rate with temperature identified as the most sensitive parameter. Therefore, despite the observed errors when comparing the two models, the lumped-capacitance model accurately represented the reaction yields and proved to be suitable for simulations involving a large number of particles, facilitating optimization studies. [ABSTRACT FROM AUTHOR]

Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability. [ABSTRACT FROM AUTHOR]

Children living with achondroplasia are at an increased risk of developing neurological complications, which may be associated with acute and life-altering events. To remediate this risk, the timely acquisition of effective neuroimaging that can help to guide clinical management is essential. We propose imaging protocols and follow-up strategies for evaluating the neuroanatomy of these children and to effectively identify potential neurological complications, including compression at the cervicomedullary junction secondary to foramen magnum stenosis, spinal deformity and spinal canal stenosis. When compiling these recommendations, emphasis has been placed on reducing scan times and avoiding unnecessary radiation exposure. Standardized imaging protocols are important to ensure that clinically useful neuroimaging is performed in children living with achondroplasia and to ensure reproducibility in future clinical trials. The members of the European Society of Pediatric Radiology (ESPR) Neuroradiology Taskforce and European Society of Neuroradiology pediatric subcommittee, together with clinicians and surgeons with specific expertise in achondroplasia, wrote this opinion paper. The research committee of the ESPR also endorsed the final draft. The rationale for these recommendations is based on currently available literature, supplemented by best practice opinion from radiologists and clinicians with subject-specific expertise. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA) undergoes degradation through the action of microorganisms and enzymes that can degrade it by composting. The goal of this work was to observe the degradation/disintegration behavior in garden soil of neat PLA and PLA composites with 3 wt% cellulose nanocrystals (CNC) modified or not with non-ionic surfactants (S) at a weight ratio of 1:1 (CNC:S). Four types of non-ionic surfactants with hydrophilic-lipophilic balance (HLB) ranging from 4.3 to 16.7 were tested: sorbitan monolaurate (Span 20), sorbitan monooleate (Span 80), polyoxyethylene sorbitan monolaurate (Tween 20) and polyoxyethylene sorbitan monooleate (Tween 80). Films were obtained by solution casting, cut into 2 × 2 cm strips and buried in garden soil, while monitoring the temperature and humidity for 150 days. Changes in the films by visual inspection, polarized light microscopy, thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR) were observed. Results showed that the addition of surfactants favored the rate of biodegradation of the composites, being the lowest molecular weight the determinant property of the surfactant to enhance biodegradation rate of PLA/CNC/S composites. Nevertheless, for surfactants belonging to the same chemical family, the highest biodegradation rate for PLA/CNC/S composite obeys the principle of high HLB, and low spherulite size. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to explore the benefits and controversies that telemedicine (TM), applied to patients with heart failure (HF), can provide in terms of diagnosis, therapeutic management, and prognosis improvement. Recent Findings and Summary: During the coronavirus disease 19 (COVID-19) outbreak, TM emerged as the most effective and feasible method available to ensure continuous care for chronic diseases. Among these, HF, characterized by high mortality, morbidity, and the need for frequent visits, may benefit of the TM role. HF patients are affected by frequent exacerbations undergoing a progressive prognosis impoverishment, strongly depending on the disease's management. A precise clinical handling is always required, with a constant optimization of the therapy, a continuous control of risk factors, and a sensitive attention to any change in symptoms, clinical signs, and laboratory tests. In this context, TM has shown to improve therapy adherence and HF: patients' self-care, impacting the prognosis even if specific results are controversial. Major evidence shows that TM may allow an adequate primary prevention, reducing the impact of the main cardiovascular risk factors. TM can also be useful for the secondary prevention, early detecting a likely HF exacerbation before it becomes clinically manifest, thereby lowering the need for hospitalization. Moreover, an optimal up-titration of the therapy and an increase in treatment adherence are feasible by using TM. However, some studies did not show unambiguous results, and uncertainties still remain. [ABSTRACT FROM AUTHOR]

During a research of digeneans (Platyhelminthes: Trematoda) infecting leaf-nosed bats (Chiroptera: Phyllostomidae) from the Kawsay Biological Station in Madre de Dios, southeastern Peru, four new species were described based on light and scanning electron microscopy (SEM): Anenterotrema paramegacetabulumn. sp. from the seba's short-tailed bat Carollia perspicillata Linnaeus, A. hastatin. sp., A. kawsayensen. sp., and A. peruensen. sp. from the greater spear-nosed bat Phyllostomus hastatus (Pallas). Anenterotrema paramegacetabulumn. sp. differs from all congeners by having a terminal oral sucker, a transversely elongated ventral sucker without clamp-shaped, and by having the testes located immediately posterior to ventral sucker. Anenterotrema hastatin. sp. is easily differentiated from the other congeneric species by having an almost clamp-shaped oral sucker, well-developed cirrus sac, a bilobulated seminal receptacle, and a group of well-developed unicellular glands located anterolateral to cirrus sac. Anenterotrema kawsayensen. sp. is characterized by possessing protuberances on the anterior margin of the oral sucker. Anenterotrema peruensen. sp. is mainly characterized by having the testes located principally anterior to ventral sucker and the cirrus sac located perpendicular to midline of the body. The present finding brings to 12, the number of known species of Anenterotrema. A key to the species of Anenterotrema Stunkard, 1938 is provided. [ABSTRACT FROM AUTHOR]

Hedruris moniezi Ibáñez & Córdova, 1976 (Nematoda: Hedruridae) was described using light and scanning electron microscopy (SEM) based on specimens collected from the stomach of Telmatobius culeus (Anura: Telmatobiidae) in Peru. We observed some characteristics not reported previously, including sessile and pedunculated papillae and amphid on the pseudolabia, bifid deirids, morphology of the retractable chitinous hook, morphology and arrangement of the plates on ventral surface of the posterior end of the males, and arrangement of caudal papillae. Telmatobius culeus represents a new host of H. moniezi. In addition, H. basilichtensis Mateo, 1971 is considered to be a junior synonym of H. oriestae Moniez, 1889. A key to valid species of Hedruris in Peru is provided. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). Methods: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. Results: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. Conclusions: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. Clinical relevance statement: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. Key Points: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. [ABSTRACT FROM AUTHOR]

Arginase is a potential target of drugs against Leishmania spp. Natural products can be a source of arginase inhibitors. This study has investigated whether the bark and leaves of Drimys brasiliensis Miers (Winteraceae), a plant known for its antileishmanial effect, can inhibit Leishmania amazonensis arginase. IC50 values of 13.6 and 8.0 μg/mL were obtained for the ethanolic extracts from D. brasiliensis bark and leaves, respectively. Liquid chromatography–high resolution mass spectrometry analysis of the bioactive extracts helped to identify ten compounds, including flavonoids, phenolic acids, and hydroxycinnamic acid derivatives. Among these compounds, flavonoids and chlorogenic acid are known for potentially inhibiting arginase, and the presence of flavonoids corroborates the leishmanicidal and antimalarial potential of the bioactive extracts. Tandem mass spectrometry (MS/MS), molecular networking and docking analysis (docking scores) showed that compounds commonly found in D. brasiliensis bark and leaves namely chlorogenic acid (2a) (−11.94 kJ/mol), coumaroylquinic acid (2b) (−13.45 kJ/mol), hydroxybenzaldehyde (3a) (−9.95 kJ/mol), and dihydroxybenzoic acid (3b) (−13.64 kJ/mol), might interact with arginase. Compounds 3a and 3b inhibited L. amazonensis arginase in vitro; the IC50 values were 175.9 ± 16.9 and 4.72 ± 0.57 µM, respectively. Combining MS/MS and computational calculation of the bioactive extracts proved an effective strategy to identify bioactive compounds in D. brasiliensis bark and leaves. [ABSTRACT FROM AUTHOR]

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC→DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ−1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ−1 in the adult ACC→DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC→DMS neurons rescues or phenocopies the behaviors of the α2δ−1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion. The role of synaptogenesis during the acquisition of goal-directed behaviors is unknown. Here, the authors show that learning-induced synaptogenesis in the adult mouse cortex is required to excite a specific circuit to adjust effort exertion. [ABSTRACT FROM AUTHOR]

Background: Granular Cell Odontogenic Fibroma (GCOF) is a rare odontogenic neoplasm reported over time with different names. The purpose of this study is to review all available data on the GCOF in the scientific literature, with a summary of all reported cases and a report of a new case. Methods: This review was conducted following the PRISMA guidelines. An electronic search was performed up to November 2022. Results: Thirty-nine studies reporting fifty-three cases were included. GCOF is a rare neoplasm among the odontogenic tumors, with a higher prevalence in women of the middle-aged and white population. This lesion occurs mostly on the posterior region of the mandible. Furthermore, based on clinical, radiographic, and histopathologic features, conservative treatment was the most reported choice with recurrence reported in two cases. Conclusion: GCOF remains controversial due to the still unsolved histogenesis. [ABSTRACT FROM AUTHOR]

A field study was carried out in the Metropolitan Area of Monterrey (MAM), the second most populated city in Mexico, characterized by increasing urbanization, high traffic density, and intense industrial activity. These characteristics commonly present high concentrations of air pollutants leading to the degradation of air quality. PM2.5 was analyzed for heavy metals at two urban sites located within the MAM (Juarez and San Bernabe) in order to determine sources, health risk, morphology, and elemental content during the COVID-19 pandemic (autumn 2020 and spring 2021). Twenty-four-hour samples of PM2.5 were collected at each site during 30-day periods using high-volume equipment. Gravimetric concentrations and 11 metals were measured (Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Ni, Cr, and Pb) by different analytical techniques (flame atomic absorption spectroscopy, graphite furnace atomic absorption spectroscopy, and inductively coupled plasma optical emission spectroscopy). Selected samples were analyzed by scanning electron microscopy-energy-disperse spectroscopy in order to characterize their morphology and elemental content. PM2.5 concentrations exceeded the Mexican standard and WHO guidelines in Juarez during spring 2021. Cu, Cd, and Co were highly enriched by anthropogenic sources, and Ni, K, Cr, and Pb had a moderate enrichment. Mg, Mn, and Ca were of crustal origin. Bivariate statistics and PCA confirmed that alkaline metals originated from crustal sources and that the main sources of trace metals included traffic emissions, resuspension from soil/road dust, steel industry, smelting, and non-exhaust emissions at both sites. Lifetime cancer risk coefficients did not exceed the permissible levels established by EPA and WHO, implying that local residents are not at risk of developing cancer. Non-carcinogenic risk coefficients revealed that there is a possible risk of suffering cardiovascular and respiratory diseases due to inhalation of cobalt at the study sites. [ABSTRACT FROM AUTHOR]

Subterranean estuaries, i.e., the mixing zone between terrestrial groundwater and recirculated seawater, host a wide range of microbiota. Here, field campaigns were conducted at the mouth of the subterranean estuary at the Sanggou Bay (Shandong Province, China) over four consecutive seasons at a seepage face (0–20 cm depth). The diversity of benthic microbiome was characterized via 16S rRNA gene sequencing and metagenomics, combined with physic-chemical parameters, e.g., organic carbon, total nitrogen and sulfate contents in sediments. During spring, the dominant species were assigned to the phylum Proteobacteria. Important opportunistic species was assigned to Acidobacteria, Actinobacteria and Bacteroidetes. The key components were identified to be species of the genera Pseudoalteromonas, Colwellia and Sphingobium, indicating the involvement of sediment microbiota in the degradation of sedimentary organic carbon, particularly that of pelagic origin, e.g., phytoplankton detritus and bivalve pseudo-feces. During spring, the microbial community was statistically similar along the depth profiles and among the three sampled stations. Similar spatial distributions were obtained in the remaining seasons. By contrast, the dominant species assemblages varied significantly among seasons, with key genera being Thioprofundum and Nitrosopumilus during summer and autumn and Thioprofundum and Ilumatobacter during winter. Network analysis revealed a seasonal shift in benthic nitrogen and sulfur metabolism associated with these variations in microbial community composition. Overall, our findings suggested that macro elements derived from pelagic inputs, particularly detrital phytoplankton, shaped the microbial community compositions at the seepage face, resulting in significant seasonal variations, while the influence of terrestrial materials transported by groundwater on the sediment microbiota at the seepage face found to be minor. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH). Recent Findings: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. Summary: New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH. [ABSTRACT FROM AUTHOR]

Background: Periventricular nodular heterotopia (PVNH) is a congenital brain malformation often associated with seizures. We aimed to clarify the spectrum of epilepsy phenotypes in PVNH and the significance of specific brain malformation patterns. Methods: In this retrospective cohort study, we recruited people with PVNH and a history of seizures, and collected data via medical record review and a standardized questionnaire. Results: One hundred individuals were included, aged 1 month to 61 years. Mean seizure onset age was 7.9 years. Ten patients had a self-limited epilepsy course and 35 more were pharmacoresponsive. Fifty-five had ongoing seizures, of whom 23 met criteria for drug resistance. Patients were subdivided as follows: isolated PVNH ("PVNH-Only") single nodule (18) or multiple nodules (21) and PVNH with additional brain malformations ("PVNH-Plus") single nodule (8) or multiple nodules (53). Of PVNH-Only single nodule, none had drug-resistant seizures. Amongst PVNH-Plus, 55% with multiple unilateral nodules were pharmacoresponsive, compared to only 21% with bilateral nodules. PVNH-Plus with bilateral nodules demonstrated the highest proportion of drug resistance (39%). A review of genetic testing results revealed eight patients with pathogenic or likely pathogenic single-gene variants, two of which were FLNA. Five had copy number variants, two of which were pathogenic. Conclusions: The spectrum of epilepsy phenotypes in PVNH is broad, and seizure patterns are variable; however, epilepsy course may be predicted to an extent by the pattern of malformation. Overall, drug-resistant epilepsy occurs in approximately one quarter of affected individuals. When identified, genetic etiologies are very heterogeneous. [ABSTRACT FROM AUTHOR]

The aim was to assess the lifetime prevalence of psychiatric comorbidity (PC) in Brazilian euthymic individuals with bipolar disorder type I, and investigate its effects on clinical outcomes and functioning. A group of 179 outpatients with BD-I in the recuperation phase were assessed, of whom 75 (41.9%) had PC and 104 (58.1%) had not. Both groups were compared using sociodemographic/clinical questionnaire, Structured Clinical Interview for DSM-IV axis I and II, Sheehan Disability and Barratt Impulsiveness Scales. Patients with PC presented less religious affiliation, more history of lifetime psychotic symptoms, rapid cycling, suicide attempts, worse scores of functioning, and higher prevalence of personality disorders. Ordinal logistic regression indicated that PC was associated with increased odds of worse levels of disability. Therefore, it could be observed that patients with BD evaluated only in euthymia presented a high mental disorders comorbidity. Considering their burdensome impact, appropriate management is a challenging reality and a crucial factor in reducing morbidity and mortality associated with BD. Further longitudinal studies on their relationship may broaden interventions to reduce patient's suffering. [ABSTRACT FROM AUTHOR]

Purpose of Review: Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management. Recent Findings: Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. Summary: miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis. [ABSTRACT FROM AUTHOR]

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell–cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with "Pitt-Hopkins-like syndrome-1" (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype–phenotype correlation. Patients (M:F 14:8) were aged between 3 and 19 years and affected by global developmental delay (GDD) (n = 21), moderate to profound intellectual disability (n = 17) and epilepsy (n = 21). Seizures mainly started in the first two years of life (median 22.5 months). Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. Autism spectrum disorder (ASD) and/or other neuropsychiatric comorbidities were present in nine patients (40.9%). Nonspecific midline brain anomalies were noted in most patients while focal signal abnormalities in the temporal lobes were noted in three subjects. Genotype–phenotype correlation was performed by also including 50 previously published patients (15 mono- and 35 bi-allelic variants). Overall, GDD (p < 0.0001), epilepsy (p < 0.0001), hyporeflexia (p = 0.012), ASD (p = 0.009), language impairment (p = 0.020) and severe cognitive impairment (p = 0.031) were significantly associated with the presence of biallelic versus monoallelic variants. We have defined the main features associated with biallelic CNTNAP2 variants, as severe cognitive impairment, epilepsy and behavioral abnormalities. We propose CASPR2-deficiency neurodevelopmental disorder as an exclusively recessive disease while the contribution of heterozygous variants is less likely to follow an autosomal dominant inheritance pattern. [ABSTRACT FROM AUTHOR]