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The accurate flux calibration of observational data is vital for astrophysics and cosmology because absolute flux uncertainties of stellar standards propagate into scientific results. With the ever higher precision achieved by telescopic missions (e.g. JWST) in the infrared (IR), suitable calibrators are required for this regime. The basis of the Hubble Space Telescope (HST) flux scale is defined by model fits of three hot (⁠|${T_\mathrm{eff}} > 30\, 000$|  K) hydrogen-atmosphere (DA) white dwarfs, which achieve an accuracy better than 1 per cent at optical wavelengths but falls below this level in the IR range. We present a network of 17 cooler DA white dwarfs with |${T_\mathrm{eff}} < 20\, 000$|  K as spectrophotometric flux standards that are equally, if not more, accurate at IR wavelengths. Cooler white dwarfs do not suffer from non-local thermal equilibrium effects in continuum flux or from ultraviolet metal line blanketing, have a larger sky density, are generally closer to Earth with little or negligible interstellar reddening, and have energy distributions peaking in the optical or near-IR. Using the latest grid of DA local thermal equilibrium atmosphere models with three-dimensional convection, the observed Space Telescope Imaging Spectrometer (STIS) and Wide Field Camera 3 (WFC3) fluxes of our network are accurate to 3 per cent over most of the range |$1450\!\! - \!\!16\, 000$|  Å, with a median standard deviation of 1.41 per cent. Fitting the HST STIS and WFC3 white dwarf spectral energy distributions (SEDs) and Balmer lines independently yields SEDs that agree within |$3\sigma$|⁠ , which demonstrates the precision of the models for our network. [ABSTRACT FROM AUTHOR]

STR loci localized on the X chromosome provide information additional to the autosomal markers routinely analyzed in forensic genetics, integrating genetic systems as Y-STRs and mitochondrial DNA in the investigation of complex kinship scenarios and mass disaster cases. In this study we genotyped 12 X-STR loci in 251 male samples from four populations of Namibia in southern Africa using the Investigator Argus X-12 kit (Qiagen, Hilden, Germany). Forensic efficiency parameters indicated high power of discrimination in the considered populations. As part of our investigation, we highlighted partial linkage associations between loci within known linkage groups (LGs) and identified several occurrences of previously unreported out-of-ladder (OL) alleles. Genetic distances between the Namibian populations here investigated and other African (Eritrea, Ethiopia, Somalia, Guinea, Cape Verde) and non-African (Germany, China, Philippines) populations using loci grouped in LGs mirrored their biogeographical distribution differently for each linkage group. Haplotype sharing within each LG revealed a high degree of population-specific types, hinting to the potential of these markers for ancestry applications. These results highlight the importance to produce specific and freely available population databases especially for multi-ethnic countries. This novel dataset is expected to be of interest for population studies that need an accessible reference dataset of African regions not currently well represented, as well as possible relevance for forensic applications focusing on the biogeographic origin of samples. [ABSTRACT FROM AUTHOR]

In the context of an increasing interest towards the safe introduction of technologies that can help human drivers while performing their driving tasks in the ordinary traffic, the proposed work provides a contribution, investigating safety-related aspects of assisted vehicles in a simulated environment, by considering other driving behavioral parameters. In particular, the influence of Adaptive Cruise Control (ACC), combined with driver distraction and route familiarity, on the driving behavior was investigated using a driving simulator. A sample of 37 drivers, aged between 21 and 34 years performed the driving tests in the simulator environment, with different scenarios applied to one road section. The interactions between a lead vehicle and a follower were investigated, collecting the kinematic parameters of the vehicle (speed, acceleration) and its position in the road (lateral position and distance from the lead vehicle) either with or without active ACC conditions. Driving simulation scenarios differed among each other not only for the ACC turned on or off, but also for the secondary tasks presented to the drivers in specific time frames of the test. Moreover, tests were repeated to induce a route familiarity effect and to study its influence on driving behavior, thus on safety. Results highlighted that the active ACC was correlated with more cautious behaviors, in terms of speed, deceleration/acceleration and distance from the lead vehicle. Women drivers were associated to a greater variability in the driving behavior. The visual distraction induced by secondary tasks appeared to have negative effects on safety-related driving performances, especially when the secondary task was highly demanding. On the other hand, when drivers became familiar with the route, they performed more aggressive driving patterns. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Discussion To conduct a retrospective cross‐sectional multicenter study to validate the relationships between migraine‐associated symptoms.Symptoms associated with headache—photophobia and phonophobia, nausea, and/or vomiting—are required criteria for migraine diagnosis based on the International Classification of Headache Disorders‐Third Edition (ICHD‐3). However, individuals with migraine report high rates of other symptoms (e.g., lightheadedness, difficulty thinking). We recently completed a single‐center study assessing the relationships between an expanded set of migraine‐associated symptoms.A pre‐registered cross‐sectional multicenter retrospective analysis was conducted on standardized questionnaire data of youth ages 6–17 years from two headache registries at pediatric tertiary care centers. Cluster Analysis of Migraine‐associated Symptoms (CAMS) was implemented to assess associations between 11 migraine‐associated symptoms. We explored differences between the two centers, and how CAMS was associated with demographics, including sex and age, and headache burden.There were 10,721 participants who were 66.5% female and had a median (interquartile range) age of 13 (10–15) years. The first three CAMS dimensions accounted for 46.5% of the variance and were consistent across sites. The first dimension indicated those reporting any migraine‐associated symptoms were likely to report multiple. The second dimension separated symptoms into those included in ICHD‐3 migraine diagnostic criteria and non‐ICHD symptoms (e.g., lightheadedness, difficulty thinking). The third dimension separated sensory hypersensitivity and vestibular symptoms. An abundance of migraine‐associated symptoms correlated with greater headache severity (Spearman's ρ = 0.18, 95% confidence interval [CI] 0.17–0.20; small effect size) and disability (ρ = 0.26, 95% CI 0.25–0.28; small effect size). We also observed differences in associated symptoms across age and sex.Associations between an expanded set of migraine‐associated symptoms are informative for headache burden and reveal intriguing changes across child development and sex. We were able to replicate findings across two centers, indicating that these symptom clusters are inherent to migraine. [ABSTRACT FROM AUTHOR]

Objectives Background Methods Results Conclusion We used Cluster Analysis of Migraine‐associated Symptoms (CAMS) to critically evaluate current International Classification of Headache Disorders‐Third Edition (ICHD‐3) migraine‐associated symptoms criteria.Diagnostic criteria play a central role in guiding clinical trial inclusion, and therefore available treatments. Migraine and tension‐type headaches (TTH) are differentiated in ICHD‐3 by many headache characteristics, including associated symptoms. A diagnosis of probable migraine indicates some but not all features of migraine are met. Photophobia and phonophobia, or nausea and/or vomiting, are required to meet a diagnosis of migraine; however, CAMS—a model that describes associated symptoms across youth with headache—indicates that a broader range of symptoms contain information about migraine burden.In this multisite retrospective cross‐sectional study, we evaluated ICHD‐3 migraine criteria. Youth aged 6–17 years with migraine (including probable migraine) or TTH were included in the analysis. We used CAMS to evaluate the migraine‐associated symptom criterion. With CAMS as a guide, we evaluated how changes to the migraine‐associated symptom criterion altered who met the diagnosis of migraine.Of the 9017 participants included in this study, 66.7% were female and had a median (interquartile range) age of 13 (10–15) years. Most participants had migraine or probable migraine (99.0%), and the remainder had TTH (1.0%). A sizable percentage (10.1%) of youth under the umbrella diagnosis of migraine were diagnosed with probable migraine because they did not meet migraine‐associated symptom criterion D; however, many in this group reported several non‐ICHD migraine‐associated symptoms. We explored alterations to criterion D based on CAMS. Allowing for photophobia or phonophobia re‐categorized 55.6% of youth as having migraine, though some only had one symptom. Including lightheadedness or lightheadedness and spinning re‐categorized 19.7% and 25.8% of youth with migraine, respectively, but all of those who were re‐categorized had at least two migraine‐associated symptoms.The ICHD‐3 captures the most prevalent migraine‐associated symptoms; however, many youths with probable migraine who do not meet full criteria due to insufficient associated symptoms nonetheless experience multiple non‐ICHD migraine‐associated symptoms. Changes to criterion D should be considered for the ICHD‐4. [ABSTRACT FROM AUTHOR]

Background: diatoms are unicellular algae that have been used for more than a century for forensic purposes to diagnose drowning, with more or less success depending on the historical era. Although many years have passed, scientific research on diatoms has never ceased, which testifies to their enduring allure in forensics. Of course, diatom research has evolved and expanded over time, changing with the availability of new techniques and technologies. The volume of articles and their production over a period of many years has resulted in old, current, and new knowledge on diatoms being scattered over a large number of books and articles. Objectives: the purpose of this narrative literature review is, therefore, to summarize all this information and bring it together in a single work that can be useful for those who are studying diatoms and their usefulness for forensics for the first time, for those who are looking for proven methods of analysis, and finally for those who are interested in exploring new frontiers of research. Methods: a comprehensive literature search that included all studies dealing with the applications of diatoms in forensic science was performed in the most popular electronic databases. Results: traditional methods have been complemented by molecular and imaging methods and, more recently, by artificial intelligence. In addition, new biological substrates have been found for the analysis of diatoms. Conclusions: all this has led, on the one hand, to the consolidation of a whole body of knowledge on diatoms, on which this forensic analysis is still based, and, on the other hand, has opened up numerous new research directions. [ABSTRACT FROM AUTHOR]

The new key biodiversity areas (KBA) standard is an important method for identifying regions of the planet‐hosting unique biodiversity. KBAs are identified through the implementation of threshold‐based criteria that can be applied to any target species and region. Current methods to rapidly assess the existence of potential KBAs in different areas of the planet still present important challenges, although they are needed to accelerate the KBA identification process for large numbers of species globally. We developed a methodology to scan geographical regions and detect potential KBAs under multiple criteria. We tested the methodology on 59 species of reptiles and amphibians in Italy through the application of selected KBA criteria. Potential KBAs were identified for multiple species under most criteria, covering 1.4%–12% of the study area, depending on analytical settings. Cell size used to identify KBAs played an important role in shaping the distribution of potential KBAs, also affecting the overlap between areas triggered by different criteria. New potential KBAs identified in this study are only partially coincident with current KBAs in Italy (previously identified for birds) and within the national protected areas. [ABSTRACT FROM AUTHOR]

Prosecco wine has become one of the widest diffused sparkling wine with 627 million bottles produced in 2021 compared to 140 million bottles produced in 2010. The spread of the product is due to a rapid growth in production capacity that has allowed a large amount of product to be placed on the market at very competitive prices. The growth of the sector has led to a radical change in the characteristics of supply with the emergence of companies with a business model based on trading, not integrated in wine production, focused on bottling and selling the product. The paper analyzes, using a System Dynamics approach, the process that determined the affirmation of the trading business model by identifying the critical variables and the relevant feedback loops structures. Resource dynamic analysis allowed us to evaluate the long-term sustainability of the dominant business model. [ABSTRACT FROM AUTHOR]

Objective: To provide healthcare professionals guidance on youth at risk for prolonged recovery and post‐traumatic headache (PTH), and on pharmacologic and non‐pharmacologic management of PTH due to concussion and mild traumatic brain injury. Background: Headache is the most common persistent post‐concussive symptom affecting 8% of youth for >3 months after concussion. Over the past decade, many studies have explored the treatment of PTH in youth, but there are no established guidelines. Methods: This white paper is based on a synthesis of an updated systematic review of the literature on treatment of PTH and a narrative review of the literature on risk factors for prolonged recovery and health disparities. Results were interpreted by a group of expert providers in PTH in children and adolescents through collaboration of the PTH and pediatric special interest groups of the American Headache Society. Results: Factors that consistently were associated with prolonged recovery from concussion and persistent PTH included female sex, a high number of acute symptoms, and adolescent age. Social determinants of health also likely play an important role in PTH and deserve consideration in the clinical and research settings. A total of 33 studies met the criteria for inclusion in the systematic review of PTH treatment in youth, although most were retrospective and of fair‐to‐poor quality. Treatment strategies included acute and preventive pharmacologic management, procedures, neuro‐modulatory devices, physical therapy, physical activity, and behavioral health support. A collaborative care approach that includes a thoughtful combination of these management strategies is likely most effective. Conclusions: This white paper provides a roadmap for tailoring the treatment of PTH based on factors influencing prolonged headache, the timing of therapies, and therapies with the most evidence for treating PTH in youth. We also highlight research needed for developing more definitive guidelines on PTH management in youth. Plain Language Summary: Post‐traumatic headache (PTH) following concussion is a common and potentially disabling condition impacting youth, yet there are no standards for treatment. This article reviews current evidence and identifies knowledge gaps to guide future research. Based on the limited available evidence and expert opinion, we offer a roadmap for the treatment of PTH in children. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. Methods: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. Results: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. Conclusions: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay. [ABSTRACT FROM AUTHOR]

To date, synovial fluid has not been the subject of targeted analysis as a possible substrate to search for the presence of diatoms in the forensic context of drowning. However, its unique characteristics of production and isolation from the external environment could make it suitable for this purpose, similar to what has already been demonstrated in the literature for vitreous humor. By considering this, synovial fluid was analyzed in a specific case that came to our attention, where the coexisting signs of polytrauma and drowning were documented during autopsy, demonstrating a period of vitality during immersion. After a thin smear of the supernatant was obtained from the centrifugation of the synovial fluid sample, diatoms were successfully detected, consistent with those found in other organs and the water of the canal. The detection of diatoms in the synovial fluid was an objective finding, but its generalizability is limited because this was a pilot application. However, in cases where death by drowning is suspected and the body has multiple areas breached by trauma, the technique of analyzing diatoms in the synovial fluid could have great potential. Therefore, it is appropriate to further explore this technique in order to obtain more forensic evidence in such a setting. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP. Methods: This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life–Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed. Results: Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged. Conclusions: Patisiran largely stabilised disease in patients with ATTRv amyloidosis. [ABSTRACT FROM AUTHOR]

Purpose In high-acuity situations such as cardiac arrest, clinicians rely on prepared medications stocked in code carts to provide timely and accurate pharmacotherapy. We examined shortage trends for medications commonly used in code carts. Methods Drug shortage data from 2001 to 2022 were retrieved from the University of Utah Drug Information Service (UUDIS) to characterize shortages reported for commonly used code cart medications. Data extracted included the number of shortages, shortage duration, drug characteristics, and reason for the shortage. Results From 2001 to 2022, 71 drug shortages for code cart medications were reported. The number of new shortages peaked in 2010, and the number of total shortages peaked in 2010. At the end of the study period, 61 (84.7%) shortages had been resolved. For resolved shortages, the mean shortage duration was 18.2 months. The drug with the greatest number of reported shortages was dextrose (10 total), the drug with the longest resolved shortage was calcium chloride injection (116 months), and the drug with the longest active shortage was atropine injection (165 months at the end of the study period). Throughout the entire study period, only 2 suppliers provided commercially available prefilled syringes of dextrose for stocking on code carts. The most common reason for shortages, when reported, was manufacturing delays. Conclusion Medications commonly used in code carts were frequently impacted by drug shortages, which have the potential to impact patient care. Institutional protocols for mitigation and larger efforts to promote a more resilient drug supply chain are critical to ensure patient safety and quality care. [ABSTRACT FROM AUTHOR]

Monitoring programs are pivotal to establishing sound management. Due to economic, logistic, and time limitations, monitoring programs often overlook differences among life‐history stages. However, species occurrence does not necessarily mean population viability, and it is unclear to what extent monitoring programs that do not consider separately adult presence and reproduction provide effective management indications. Unfortunately, collecting data on certain life stages requires high sampling effort, leading to a trade‐off between model reliability and resources needed for monitoring. We collected data on presence and reproduction of amphibians by monitoring 207 waterbodies in Lombardy (northern Italy) in 2017–2022. We then used multistate occupancy models to test whether certain environmental features, namely, pond area, hydroperiod, forest cover, shade, aquatic vegetation, and predators’ presence, differentially affected adult occurrence and breeding probabilities of multiple amphibian species. To assess optimal sampling efforts, we modeled the detection probabilities of adults and reproduction across multiple species. Finally, we identified the optimal monitoring strategy under different scenarios of resource availability, comparing adult‐only monitoring versus joint assessment of the occurrence of adults and reproduction. In many cases, the main drivers of adult occurrence and reproduction did not coincide because most investigated ecological variables affected one life stage or the other. Forest area, for instance, increased occurrence probabilities of adults of the endemic Rana latastei but showed no effect on their reproduction probabilities. Quantitative estimates of the sampling effort showed that occurrence of adults was easier to spot in 4 out of 7 species. Multicriteria decision analyses showed that when resources were scarce, monitoring adults was the optimal strategy for those 4 species. Conversely, with more resources, monitoring both adults and reproduction emerged as the best strategy for all the considered species. Integrated monitoring of adults and reproduction is essential to comprehensively identify effective conservation measures for amphibians. [ABSTRACT FROM AUTHOR]

Lowering expression of prion protein (PrP) is a wellvalidated therapeutic strategy in prion disease, but additional modalities are urgently needed. In other diseases, small molecules have proven capable of modulating pre-mRNA splicing, sometimes by forcing inclusion of cryptic exons that reduce gene expression. Here, we characterize a cryptic exon located in human PRNP’s sole intron and evaluate its potential to reduce PrP expression through incorporation into the 50 untranslated region. This exon is homologous to exon 2 in nonprimate species but contains a start codon that would yield an upstream open reading frame with a stop codon prior to a splice site if included in PRNP mRNA, potentially downregulating PrP expression through translational repression or nonsensemediated decay. We establish a minigene transfection system and test a panel of splice site alterations, identifying mutants that reduce PrP expression by as much as 78%. Our findings nominate a new therapeutic target for lowering PrP. [ABSTRACT FROM AUTHOR]

Introduction: Internet Gaming Disorder (IGD) according to DSM-5 is a behavioral addiction needing additional study. IGD in youth is correlated with anxiety, depression, attention problems, interpersonal problems, social phobia, behavior problems and low academic achievement. The aim of the present research is to contribute to the understanding of the disorder, by providing preliminary data on the factorial structure of the IGD Questionnaire in the Italian version. Participants: 612 Italian students (323 females), mean of age = 13.94 (SD = 2.44). Instruments: a survey comprising IGD Questionnaire, Internet Addiction Test (IAT), Children's Coping Strategies Checklist (CCSC-R1), Assessment of Interpersonal Relations (AIR), and Child Behavior Checklist (CBCL). Results: 15.2% of participants showed a sub-clinical IGD and 2.1% met the full diagnostic criteria. Participants with IGD showed lower scores in interpersonal relationships, worse coping strategies and higher scores in externalization. The factorial structure of the IGD Questionnaire highlights 4 factors ("addiction", "gaming as coping", "impaired control" and "negative outcomes") that explain 52.14% of the variance. A single-factor solution was also tested and results seem to be coherent with the four-factor solution, explaining less variance. Conclusions: IGD is a complex clinical condition that can be thought both as a single-factored and as a multi-faceted condition. [ABSTRACT FROM AUTHOR]

We present the first spectroscopic ALMA follow-up for a pilot sample of nine radio-selected near-IR-dark galaxies in the COSMOS field. These sources were initially selected as radio-detected sources (S3 GHz > 12.65 μJy) without an optical or near-IR (NIR) counterpart in the COSMOS2015 catalog (Ks ≳ 24.7 mag), and just three of them were subsequently detected in the deeper COSMOS2020. Several studies highlighted that this selection could provide a population of highly dust-obscured, massive, and star-bursting galaxies. With these new ALMA observations, we assess the spectroscopic redshifts of this pilot sample of sources and improve the quality of the physical properties estimated through SED-fitting. Moreover, we measure the quantity of molecular gas inside these galaxies and forecast their potential evolutionary path, finding that the radio-selected NIR-dark galaxies might likely represent a population of high-z progenitors of the massive and passive galaxies that were discovered at z ∼ 3. Finally, we present some initial constraints on the kinematics of the interstellar medium within the analyzed galaxies, reporting a high fraction (∼55%) of double-peaked lines that can be interpreted as the signature of a rotating structure in our targets or as the presence of major mergers in our sample. The results we present here show the scientific potential of (sub)mm observations for this elusive population of galaxies and highlight the potential contribution of these sources to the evolution of the massive and passive galaxies at high z. [ABSTRACT FROM AUTHOR]

The cardiac extracellular matrix (cECM) is fundamental for organ morphogenesis and maturation, during which time it undergoes remodeling, yet little is known about whether mechanical forces generated by the heartbeat regulate this remodeling process. Using zebrafish as a model and focusing on stages when cardiac valves and trabeculae form, we found that altering cardiac contraction impairs cECM remodeling. Longitudinal volumetric quantifications in wildtype animals revealed region-specific dynamics: cECM volume decreases in the atrium but not in the ventricle or atrioventricular canal. Reducing cardiac contraction resulted in opposite effects on the ventricular and atrial ECM, whereas increasing the heart rate affected the ventricular ECM but had no effect on the atrial ECM, together indicating that mechanical forces regulate the cECM in a chamber-specific manner. Among the ECM remodelers highly expressed during cardiac morphogenesis, we found one that was upregulated in non-contractile hearts, namely tissue inhibitor of matrix metalloproteinase 2 (timp2). Loss- and gain-of-function analyses of timp2 revealed its crucial role in cECM remodeling. Altogether, our results indicate that mechanical forces control cECM remodeling in part through timp2 downregulation. [ABSTRACT FROM AUTHOR]

The holographic bit threads are an insightful tool to investigate the holographic entanglement entropy and other quantities related to the bipartite entanglement in AdS/CFT. We mainly explore the geodesic bit threads in various static backgrounds, for the bipartitions characterized by either a sphere or an infinite strip. In pure AdS and for the sphere, the geodesic bit threads provide a gravitational dual of the map implementing the geometric action of the modular conjugation in the dual CFT. In Schwarzschild AdS black brane and for the sphere, our numerical analysis shows that the flux of the geodesic bit threads through the horizon gives the holographic thermal entropy of the sphere. This feature is not observed when the subsystem is an infinite strip, whenever we can construct the corresponding bit threads. The bit threads are also determined by the global structure of the gravitational background; indeed, for instance, we show that the geodesic bit threads of an arc in the BTZ black hole cannot be constructed. [ABSTRACT FROM AUTHOR]

The cardiac extracellular matrix (cECM) is fundamental for organ morphogenesis and maturation, during which time it undergoes remodeling, yet little is known about whether mechanical forces generated by the heartbeat regulate this remodeling process. Using zebrafish as a model and focusing on stages when cardiac valves and trabeculae form, we found that altering cardiac contraction impairs cECM remodeling. Longitudinal volumetric quantifications in wildtype animals revealed region-specific dynamics: cECM volume decreases in the atrium but not in the ventricle or atrioventricular canal. Reducing cardiac contraction resulted in opposite effects on the ventricular and atrial ECM, whereas increasing the heart rate affected the ventricular ECM but had no effect on the atrial ECM, together indicating that mechanical forces regulate the cECM in a chamber-specific manner. Among the ECM remodelers highly expressed during cardiac morphogenesis, we found one that was upregulated in non-contractile hearts, namely tissue inhibitor of matrix metalloproteinase 2 (timp2). Loss- and gain-of-function analyses of timp2 revealed its crucial role in cECM remodeling. Altogether, our results indicate that mechanical forces control cECM remodeling in part through timp2 downregulation. [ABSTRACT FROM AUTHOR]

Background: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies. However, the integration of BRCA testing in Italian BUs faces multiple challenges. This study, by Senonetwork Italia, aimed to evaluate genetic testing practices and identify obstacles within Italian BUs. Methods: Senonetwork Italia conducted a 16-question web-based survey involving 153 BUs. The survey assessed aspects of BRCA testing, including timing, urgency, counseling, patient selection, and multi-gene panels. Results: Of the 153 BUs, 109 (71.2%) responded. Testing before surgery was performed by 70.6% of centers, with urgent cases acknowledged by 87.2%. Most centers (56.0%) arranged urgent pre-test counseling within a week. BRCA mutation status influenced treatment decisions in 99.1% of cases. Multi-gene panels were used by 33.0% of centers for all genetic counseling cases, while 56.0% followed standard referral criteria. The main challenges included cost, reimbursement, and reporting timelines. Conclusions: This survey highlights significant variations in BRCA testing practices across Italian BUs and identifies key logistical and financial challenges. There is a need for standardized practices of genetic testing to ensure personalized and effective BC management in Italy. [ABSTRACT FROM AUTHOR]

In this response to Hartman, this issue, I integrate anti-Blackness and Indigenous theories, to ponder the ways risk is projected onto Hartman's infant niece. The "dense temporalities" of the many objects used to surveil the infant are described, along with the ways Hartman's lovely meandering associations via autotheory contribute to shifting ontologies and epistemologies. Building on Hartman's considerations of the varieties of unconscious enigmatic forms his niece is bathed in, I explore the potentials of these transmissions emanating from the dense temporal histories of the surveillance objects themselves and the ways the "human" infant perpetually comes into being only momentarily, co-emergent with these more-than-human objects along with those humans tending to her. The racialized and misogynous histories of some of these objects and their transmitted risks, can only be enigmatic and too-much. Hartman's use of the term "snatch" is also examined along with its versatility based on its meanings referring to both vaginas, vulvas, and phallic "members." [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of pegylated interferon (PEG-IFN) alpha-2a to treat post-uveitic relapsing macular edema (ME) after withdrawal of non-PEG IFN alpha-2a or 2b to maintain treatment efficacy. This retrospective study investigated subjects with post-uveitic ME who received weekly subcutaneous PEG-IFN alpha-2a injections. Comparisons between baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) and those at all follow-up visits were made. Six patients (nine eyes) were treated and followed up for six months. CMT (mean [standard deviation]) decreased from 375[117] to 283[39] μm after one month (p < 0.001), remaining significantly lower up to the final follow-up visit at six months (275[38] μm, p = 0.008), and BCVA (0.21[0.16] logMAR at baseline) showed an improvement of 0.12[0.11] logMAR (p = 0.026) at six months. Neither recurrences nor any serious adverse events were recorded. Post-uveitic ME patients were effectively and safely treated with PEG-IFN alpha-2a. [ABSTRACT FROM AUTHOR]

The article focuses on the unifying and explanatory power of the selective realism defended by Anjan Chakravartty. Our main aim is twofold. First, we critically analyse the purported synthesis between entity realism and structural realism offered by the author. We give reasons to think that this unification is an inconvenient marriage. In the second step, we deal with certain controversial aspects of the intended unification among three metaphysical concepts: causation, laws of nature and natural kinds. After pointing out that Chakravartty's conception of laws is a plausible view that a scientific realist might endorse, we contend, on the contrary, that the concept of natural kind is dispensable in the framework of Chakravartty's realism. [ABSTRACT FROM AUTHOR]

Reintroduction and rewilding initiatives are key strategies to reverse human impacts on ecosystems and re‐establish natural processes. However, rewilding may involve complex management scenarios, because many expanding species can have economic impacts and cause human–wildlife conflicts. Conflicts can be particularly challenging when carnivores, large herbivores and ecosystem engineers are involved. The Eurasian beaver (Castor fiber) is a key ecosystem engineer that was once present in a large part of the Palearctic, but in Medieval times underwent a severe decline due to the joint effects of habitat loss and hunting. Subsequent legal protection and reintroductions triggered the recovery of the species through most of its original range. Eurasian beavers recently started the recolonization of Italy, because of the joint effects of natural dispersal (from Austria to northern Italy) and illegal reintroductions (central Italy). The lack of data on the most likely colonization routes hampers appropriate management of this species. Here, we identified the areas where beaver populations are most likely to arrive in the near future within Europe, with a specific focus on Italy. First, we developed spatially cross‐validated species distribution models to identify the areas with the highest suitability for the Eurasian beaver in Europe. Second, we used connectivity modelling to assess the possible expansion routes of this species in Italy. Large areas of Europe are suitable for the beaver and may soon be colonized. The connectivity model showed a high potential for expansion from central Italy to surrounding areas, while the high isolation of northern Italy populations suggests a slower expansion. Our results can help environmental managers to understand where to focus both the future monitoring of beaver populations and actions aimed at preventing and mitigating possible human–wildlife conflicts that could arise from the expansion of an environmental engineer such as the beaver. [ABSTRACT FROM AUTHOR]

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The retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic postreceptoral channels. The goal of the current study was to determine temporal sensitivity across the three postreceptoral channels in subcortical and cortical regions involved in human vision. We measured functional magnetic resonance imaging (fMRI) responses at 7 T from three participants (two males, one female) viewing a high-contrast, flickering, spatially uniform wide field (~140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L + M + S, L - M, and S - (L +M) cone combinations. These measurements were used to create temporal sensitivity functions of the primary visual cortex (V1) across eccentricity and spatially averaged responses from the lateral geniculate nucleus (LGN), and the V2/V3, hV4, and V3A/B regions. fMRI responses reflected the known properties of the visual system, including higher peak temporal sensitivity to achromatic versus chromatic stimuli and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. The comparison of measured cortical responses to a model of the integrated retinal output to our stimuli demonstrates that extensive filtering and amplification are applied to postretinal signals. [ABSTRACT FROM AUTHOR]

Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells. [ABSTRACT FROM AUTHOR]

The present study aims to analyze the actions of former president Jair Bolsonaro and his stance as a threat to democracy, given the implementation of a militarized educational model for young students. In the approach, the trajectory of the former President of the Republic was observed from the perspective of Bolsonarism and how the implementation of the National Program for Civic-Military Schools in the Country was prioritized. [ABSTRACT FROM AUTHOR]

The widespread adoption of Internet of Things (IoT) devices in home, industrial, and business environments has made available the deployment of innovative distributed measurement systems (DMS). This paper takes into account constrained hardware and a security-oriented virtual local area network (VLAN) approach that utilizes local message queuing telemetry transport (MQTT) brokers, transport layer security (TLS) tunnels for local sensor data, and secure socket layer (SSL) tunnels to transmit TLS-encrypted data to a cloud-based central broker. On the other hand, the recent literature has shown a correlated exponential increase in cyber attacks, mainly devoted to destroying critical infrastructure and creating hazards or retrieving sensitive data about individuals, industrial or business companies, and many other entities. Much progress has been made to develop security protocols and guarantee quality of service (QoS), but they are prone to reducing the network throughput. From a measurement science perspective, lower throughput can lead to a reduced frequency with which the phenomena can be observed, generating, again, misevaluation. This paper does not give a new approach to protect measurement data but tests the network performance of the typically used ones that can run on constrained hardware. This is a more general scenario typical for IoT-based DMS. The proposal takes into account a security-oriented VLAN approach for hardware-constrained solutions. Since it is a worst-case scenario, this permits the generalization of the achieved results. In particular, in the paper, all OpenSSL cipher suites are considered for compatibility with the Mosquitto server. The most used key metrics are evaluated for each cipher suite and QoS level, such as the total ratio, total runtime, average runtime, message time, average bandwidth, and total bandwidth. Numerical and experimental results confirm the proposal's effectiveness in foreseeing the minimum network throughput concerning the selected QoS and security. Operating systems yield diverse performance metric values based on various configurations. The primary objective is identifying algorithms to ensure suitable data transmission and encryption ratios. Another aim is to explore algorithms that ensure wider compatibility with existing infrastructures supporting MQTT technology, facilitating secure connections for geographically dispersed DMS IoT networks, particularly in challenging environments like suburban or rural areas. Additionally, leveraging open firmware on constrained devices compatible with various MQTT protocols enables the customization of the software components, a crucial necessity for DMS. [ABSTRACT FROM AUTHOR]

The microscopic evaluation of hemorrhagic infiltrates is crucial in forensic diagnostics, but it proves challenging in corificated and mummified cadavers. In these cases, pre-treatment with rehydrating solutions is recommended, although their effects on the hemorrhagic infiltrate are not well understood. In this pilot study, we microscopically investigated the effect of two different rehydrating solutions—Sandison's solution and fabric softener—on well-preserved human cadaveric skin samples taken from areas affected by an ecchymotic lesion, comparing them with direct fixation in formalin. Specifically, we examined the topographic distribution of the hemorrhagic infiltrate in each layer of the skin by assigning a semi-quantitative score, conducted mutual comparisons, and performed statistical analysis. Histologically, compared to direct fixation in formalin, a slight and statistically non-significant reduction in the hemorrhagic infiltrate was observed in samples pre-treated with fabric softener. On the other hand, a more pronounced and statistically significant decrease in scores was observed in samples pre-treated with Sandison's solution. This effect is likely due to the fact that Sandison's solution, due to its components, exerts an osmotic effect, partially inducing osmotic lysis of red blood cells. Overall, extensive areas of hemorrhagic infiltrates were preserved, although to a lesser extent, while smaller foci were markedly reduced, sometimes even disappearing. The findings suggest that Sandison's solution has a detrimental effect on cutaneous hemorrhagic infiltrates, emphasizing the importance of being cautious and conducting dual sampling, using both formalin and a rehydrating solution, for forensic examination of mummified or corificated skin samples. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real‐life data in multifocal motor neuropathy (MMN) patients. Methods: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty‐six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. Results: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR:When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti‐GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%–83% of the patients. Anti‐GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. Conclusions: This study provides insights into the real‐world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria. [ABSTRACT FROM AUTHOR]

The higher‐order turbulence scheme, Cloud Layers Unified by Binormals (CLUBB), is known for effectively simulating the transition from cumulus to stratocumulus clouds within leading atmospheric climate models. This study investigates an underexplored aspect of CLUBB: its capacity to simulate near‐surface winds and the Planetary Boundary Layer (PBL), with a particular focus on its coupling with surface momentum flux. Using the GFDL atmospheric climate model (AM4), we examine two distinct coupling strategies, distinguished by their handling of surface momentum flux during the CLUBB's stability‐driven substepping performed at each atmospheric time step. The static coupling maintains a constant surface momentum flux, while the dynamic coupling adjusts the surface momentum flux at each CLUBB substep based on the CLUBB‐computed zonal and meridional wind speed tendencies. Our 30‐year present‐day climate simulations (1980–2010) show that static coupling overestimates 10‐m wind speeds compared to both control AM4 simulations and reanalysis, particularly over the Southern Ocean (SO) and other midlatitude ocean regions. Conversely, dynamic coupling corrects the static coupling 10‐m winds biases in the midlatitude regions, resulting in CLUBB simulations achieving there an excellent agreement with AM4 simulations. Furthermore, analysis of PBL vertical profiles over the SO reveals that dynamic coupling reduces downward momentum transport, consistent with the found wind‐speed reductions. Instead, near the tropics, dynamic coupling results in minimal changes in near‐surface wind speeds and associated turbulent momentum transport structure. Notably, the wind turning angle serves as a valuable qualitative metric for assessing the impact of changes in surface momentum flux representation on global circulation patterns. Plain Language Summary: The Cloud Layers Unified by Binormals (CLUBB) scheme offers a promising way to model the complexities of cloud behavior, but its impact on winds and global circulation has been less explored. In our study, we investigate how different ways of representing the complex coupling between surface drag and the lowest kilometer of the Earth's atmosphere affect global wind speeds and circulation. We specifically examine two distinct approaches: a static approach, which feeds a constant surface drag to CLUBB, and a dynamic approach, which adjusts the surface drag based on the winds updates computed by CLUBB. Over a present‐day climate, we find that static coupling tends to produce excessively large wind speeds in certain regions, like the Southern Ocean and parts of the North Atlantic and North Pacific. Instead, dynamic coupling produces excellent near‐surface wind speeds in these regions, and also over the rest of the globe. Moreover, we discover that dynamic coupling reduces the downward turbulent transport of momentum, highlighting the enhancements in near‐surface wind speeds found with this approach are physically consistent. Lastly, we use the change in wind direction with height to qualitatively evaluate how the two coupling methods affect global circulation patterns. Key Points: Dynamic coupling between Cloud Layers Unified by Binormals (CLUBB) and surface momentum flux enhances global winds climate simulations bringing CLUBB in line with control atmospheric climate modelIn midlatitude regions, the dynamic coupling enhances the boundary‐layer momentum transport compared to the static couplingThe wind turning angle turns out a useful qualitative metric, linking changes in surface momentum flux to the changes in global circulation [ABSTRACT FROM AUTHOR]

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24–48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients. [ABSTRACT FROM AUTHOR]

Nematodes are keystone actors of soil, freshwater and marine ecosystems, but the complexity of morphological identification has limited broad-scale monitoring of nematode biodiversity. DNA metabarcoding is increasingly used to assess nematode diversity but requires universal primers with high taxonomic coverage and high taxonomic resolution. Several primers have been proposed for the metabarcoding of nematode diversity, many of which target the 18S rRNA gene. In silico analyses have a great potential to assess key parameters of primers, including taxonomic coverage, resolution and specificity. Based on a recently-available reference database, we tested in silico the performance of fourteen commonly used and one newly optimized primer for nematode metabarcoding. Most primers showed very good coverage, amplifying most of the sequences in the reference database, while four markers showed limited coverage. All primers showed good taxonomic resolution. Resolution was particularly good if the aim was the identification of higher-level taxa, such as genera or families. Overall, species-level resolution was higher for primers amplifying long fragments. None of the primers was highly specific for nematodes as, despite some variation, they all amplified a large number of other eukaryotes. Differences in performance across primers highlight the complexity of the choice of markers appropriate for the metabarcoding of nematodes, which depends on a trade-off between taxonomic resolution and the length of amplified fragments. Our in silico analyses provide new insights for the identification of the most appropriate primers, depending on the study goals and the origin of DNA samples. This represents an essential step to design and optimize metabarcoding studies assessing nematode diversity. [ABSTRACT FROM AUTHOR]

Abstract:Introduction: The current state of research suggests that personal, environmental, and product-related risk factors contribute to the development and maintenance of gaming disorder. Concerning game related risk factors, evidence points to certain game features contributing to the overall risk of gaming disorder, as for example reward features, social features, and monetization features. However, no standardized instrument is available to capture risk enhancing game characteristics. Methods: Based on theoretical considerations and stepwise conducted qualitative analyses of in-game content, risk-enhancing game features were identified and specified. Furthermore, a pilot study was conducted comprising N = 4,468 students (M[Age] = 14.54 years, SD = 1.37 years). Game features of the preferred games of the students were analyzed regarding their predictive value of gaming disorder. Results: Data suggests that two features are associated most strongly with gaming disorder: 1) mandatory social interactions (β =.20), and 2) number of reward categories (β =.12). Based on these findings and further updates, the RCCG was refined and finalized. Conclusions: With the RCCG, a structured instrument to capture, describe, and evaluate risk enhancing structural characteristics of video games is available. The RCCG enables a general risk assessment of games as well as recommended age-classifications based on certain structural features unsuitable for specific age groups. [ABSTRACT FROM AUTHOR]

In 2018 a collaborative project between Politecnico di Milano (PoliMI) and Regione Lombardia (RL) was launched to join forces and expertise toward the improvement of the regional transport infrastructures maintenance management. One of the project goals was the development of regional guidelines aimed to support the design and implementation of monitoring systems for bridges. The focus of this paper is on the illustration of the Monitoring Regional (MoRe) guidelines and of their implementation on nine pilot monitoring systems designed and deployed within the project. The (MoRe) guidelines tackle the entire monitoring process from the analyses of the monitoring goals and the preliminary investigations needed to the identification of the phenomena and relevant indicators to monitor, up to the selection of monitoring devices and the presentation of results. A short illustration of the permanent monitoring systems installed on nine exemplary bridges in the Lombardia region concludes the paper. [ABSTRACT FROM AUTHOR]

Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl2-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl2-induced ALI in swine to understand toxico-pathophysiology and evaluate whether it is suitable for screening potential medical countermeasures and to identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30–40 kg) of either sex were exposed to Cl2 (≤240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl2 resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl2 exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid, vascular leakage, and pulmonary edema compared with the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro- l -tyrosine and 3,5-dichloro- l -tyrosine) were detected in plasma and lung tissue after Cl2 exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl2 inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl2 inhalation. NEW & NOTEWORTHY: We established a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute lung injury and is suitable for screening potential medical countermeasures. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers of chlorine inhalation. [ABSTRACT FROM AUTHOR]

The continuous emergence of SARS-CoV-2 variants caused the persistence of the COVID-19 epidemic and challenged the effectiveness of the existing vaccines. The viral proteases are the most attractive targets for developing antiviral drugs. In this scenario, our study explores the use of HIV-1 protease inhibitors against SARS-CoV-2. An in silico screening of a library of HIV-1 proteases identified four anti-HIV compounds able to interact with the 3CLpro of SARS-CoV-2. Thus, in vitro studies were designed to evaluate their potential antiviral effectiveness against SARS-CoV-2. We employed pseudovirus technology to simulate, in a highly safe manner, the adsorption of the alpha (α-SARS-CoV-2) and omicron (ο-SARS-CoV-2) variants of SARS-CoV-2 and study the inhibitory mechanism of the selected compounds for cell–virus interaction. The results reported a mild activity against the viral proteases 3CLpro and PLpro, but efficient inhibitory effects on the internalization of both variants mediated by cathepsin B/L. Our findings provide insights into the feasibility of using drugs exhibiting antiviral effects for other viruses against the viral and host SARS-CoV-2 proteases required for entry. [ABSTRACT FROM AUTHOR]

Despite the pandemic upending in-person clinical treatments, psychoanalysis struggles to conceptualize a frame that is truly open to a world beyond the singular, human only dyad. This article challenges psychoanalysis to blowup the frame of practice by destroying the very subject of the work – the human. Integrating key concepts from anti-blackness and indigenous theories, the author contends that the category of the human is inherently and irreparably violent; the undergirding onto-epistemological system for the formation of white settler colonial, heteropatriarchal subjectivity and its co-created violences of enslavement, dispossession, genocide, mass extinctions, and ecological destruction. Because psychoanalysis has evolved around this Enlightenment subject that renders certain people "human," and all others disposable, its frame and focus is designed to uphold, not resist, biopolitical and ecological violence. Thus, psychoanalysis is onto-epistemologically unfit and unable to effectively address social violences and the climate crisis while emanating from this exceptionalist "human." Integrating anti-blackness and indigenous theories, the author, using examples from clinical work online, proposes a different form of subjectivity, one that is co-emergent with "dense temporalities" of the more-than-human. Only through such a temporally dense, transcorporeal subject can psychoanalysis hope to subvert the world of human destruction. [ABSTRACT FROM AUTHOR]

Life expectancy among young cancer survivors has increased in the last decades. Unfortunately, young cancer survivors might still experience mental and physical issues due to cancer treatment. Moreover, although physical activity is a valid tool for increasing social support and reducing the risk of obesity, sedentary behaviour is very common among young cancer survivors. Therefore, the current pilot study aims to estimate lack of social support impact on physical activity practice on mental health and quality of life. A sample of 69 Italian young cancer survivors (60% females) were included in the study and physical activity, anxiety, depression and quality of life were assessed by self‐reported questionnaires. The results showed that a lack of social support for exercising was connected to higher depressive symptoms, while no influence was detected on anxiety. Concerning quality of life, the analysis of variance model showed a significant effect of the lack of social support on physical mobility but not on self‐care, usual activities, pain and discomfort and general health. In conclusion, integrating physical activity in young cancer survivors' lifestyle, considering cancer‐related side effects, might enhance their mental health and quality of life by providing social support at the same time. Healthcare professionals should evaluate the feasibility and support adapted physical activity programmes for young cancer survivors, to reduce the risk of depression and obesity, among others. [ABSTRACT FROM AUTHOR]

Intense physical activity can induce metabolic changes that modify specific biochemical biomarkers. In this scenario, the purpose of our study was to evaluate how intense physical activity can affect oxidative metabolism. Following this, fifteen professional basketball players and fifteen sedentary controls were recruited and subjected to two samplings of serum and urine in the pre-season (September) and two months after the start of the competitive season (November). Our results have shown an increase in athletes compared to controls in CK and LDH in September (respectively, p-value 0.003 and p-value < 0.001) and in November (both p-value < 0.001), whereas ALT is increased only in November (p-value 0.09). GGT serum levels were decreased in athletes compared to controls in both months (in September p-value 0.001 and in November p-value < 0.001). A gene expression analysis, carried out using RT-PCR, has revealed that IL-2, IL-6, IL-8, xCT and GCLM are increased in athletes in both months (p-value < 0.0001), while IL-10 and CHAC1 are increased only in September if compared to the controls (respectively, p-value 0.040 and p-value < 0.001). In conclusion, physical activity creates an adaptation of the systems involved in oxidative metabolism but without causing damage to the liver or kidney. This information could be of help to sports doctors for the prevention of injuries and illnesses in professional athletes for the construction of the athlete's passport. [ABSTRACT FROM AUTHOR]

Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients. Methods: We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020. Results: A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis. Discussion: PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients. [ABSTRACT FROM AUTHOR]

This document is an introduction to a special issue of the Journal for General Philosophy of Science, focusing on the work of philosopher Anjan Chakravartty. Chakravartty is known for his research on scientific realism and anti-realism, as well as his contributions to metaphysics and the philosophy of science. The special issue includes articles by various authors discussing Chakravartty's ideas and theories, with Chakravartty providing responses and comments. The topics covered in the articles include the relationship between science and metaphysics, the explanatory power of dispositional realism, the problem of conflicting scientific models, and epistemic disagreements in scientific ontology. Chakravartty also offers his own reflections on these topics in his article. [Extracted from the article]

This paper reports the energies and charge and spin distributions of both the vertically excited and fully relaxed GR1 states of the neutral singlet vacancy in diamond obtained from direct Δ-SCF calculations used previously to describe the low-lying excited states in AFII NiO and α-Al2O3. The calculations are based on the B3LYP functional in its standard form, with a C basis set that is identical to that which was used previously in numerous calculations of the ground state properties of defective diamond. Both the vertically excited and thermally relaxed GR1 states are predicted to be excitonic and insulating, with extensive re-distribution of charge and spin density and back-donation to the donor site. The present calculations suggest that the triplet state makes no contribution to the GR1 excitation. The predicted energy of the zero phonon line (1.57 eV) compares with the observed value of 1.67 eV, which also suggests that the GR1 state is neutral. The bandgaps lead to an estimate of the next higher (GR2) excited state energy, which is close to that found in the observed spectra. Similar calculations are used to predict the energies of the higher gap states at (5.0–5.5) eV, including the bulk value of 7.3 eV, which compares with the experimental value of (7.3–7.4) eV. An explanation is suggested as to why only the GR1 luminescence is observed. This paper also suggests an alternative channel for the recovery of the ground state in photoluminescence studies. [ABSTRACT FROM AUTHOR]

A one-pot, two-step process was developed for the preparation of pyrrole compounds from 2,5-dimethylfuran. The first step was the acid-catalyzed ring-opening reaction of 2,5-dimethylfuran (DF), leading to the formation of 2,5-hexanedione (HD). A stoichiometric amount of water and a sub-stoichiometric amount of sulfuric acid were used by heating at 50 °C for 24 h. Chemically pure HD was isolated, with a quantitative yield (up to 95%), as revealed by 1H-NMR, 13C-NMR, and GC-MS analyses. In the second step, HD was used as the starting material for the synthesis of pyrrole compounds via the Paal–Knorr reaction. Various primary amines were used in stoichiometric amounts. 1H-NMR, 13C-NMR, ESI-Mass, and GC-Mass analyses confirmed that pyrrole compounds were prepared with very good/excellent yields (80–95%), with water as the only co-product. A further purification step was not necessary. The process was characterized by a very high carbon efficiency, up to 80%, and an E-factor down to 0.128, whereas the typical E-factor for fine chemicals is between 5 and 50. Water, a co-product of the second step, can trigger the first step and therefore make the whole process circular. Thus, this synthetic pathway appears to be in line with the requirements of a sustainable chemical process. A pyrrole compound bearing an SH group (SHP) was used for the functionalization of a furnace carbon black (CB). The functionalized CB (CB/SHP) was utilized in place of silica, resulting in a 15% mass reduction of reinforcing filler, in an elastomeric composite based on poly(styrene-co-butadiene) from solution anionic polymerization and poly(1,4-cis-isoprene) from Hevea Brasiliensis. Compared to the silica-based composite, a reduction in the Payne effect of about 25% and an increase in the dynamic rigidity (E' at 70 °C) of about 25% were obtained with CB/SHP. [ABSTRACT FROM AUTHOR]

In a series of articles, Mauricio Suárez defends the neutrality of fictionalism with respect to the scientific realism-anti-realism debate. Suárez understands fictionalism from a strictly methodological point of view, linked to the practice of model building in the context of the philosophy of science. He moves away from the type of fictionalism analysed in other areas of philosophy such as metaphysics, the philosophy of language, aesthetics or the philosophy of mathematics. Following Vaihinger's position, he emphasizes the inferential role of fiction in scientific modelling and argues that scientific fictionalism is not incompatible with scientific realism, as is often believed. We argue against Suárez's position and reject the ubiquitous character assigned to fictions in scientific discourse, as well as the deflationary view of scientific realism defended by Suárez. We conclude that when the semantic, epistemic, and metaphysical aspects at stake in the realism-antirealism debate are taken into account, the alleged compatibility between scientific realism and fictionalism starts to generate some tension. [ABSTRACT FROM AUTHOR]

Background: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. Methods: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. Results: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. Conclusions: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission. [ABSTRACT FROM AUTHOR]

Background: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis. Methods: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations. Results: Creatinine significantly correlated with LMN damage (r = 0.38), active (r = 0.18) and chronic (r = 0.24) denervation and baseline ALSFRS-R (r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active (r = 0.35, r = 0.27, r = 0.24) and chronic (r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score (r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride (r = −0.19) and potassium levels (r = −0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57–0.86)], creatinine [HR 0.86 (95% CI 0.81–0.92)], chloride [HR 0.95 (95% CI 0.92–0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99–0.99)], and AST [HR 1.02 (95% CI 1.01–1.02)] were independently associated with survival. Conclusions: Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival. [ABSTRACT FROM AUTHOR]