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Cancer predisposition syndromes are recognized in about 10% of pediatric malignancies with several genes specifically involved in a subset of pediatric tumors such as DICER1, in pleuropulmonary blastoma, cystic nephroma, and brain sarcomas. By contrast, the role of BRCA1/2 in pediatric cancer predisposition is still under investigation. We present two cases of young first-degree cousins, both carrying a germline BRCA2 variant and developing tumors characterized by somatic DICER1 mutations. Patient 1 presented with a cystic nephroma harboring a somatic DICER1 variant (p.Asp1810Tyr), while patient 2 had a primary intracranial DICER1-mutated sarcoma showing a distinct somatic DICER1 variant (p.Asp1709Glu) as well as biallelic inactivation of TP53 (p.Val173Leu, VAF 91%) and APC (p.Ile1307Lys, VAF 95%) and a pathogenic variant in KRAS (p.Gln61His). Both patients carried the same germline BRCA2 variant (p.Arg2842Cys) of unknown significance. The same variant was found in the mother of patient 2 and in the father of patient 1, who are siblings. A homologous recombination deficiency signature was not identified in any of the two tumors, possibly suggesting a reduction of BRCA2 activity. The association of BRCA2 and DICER1 variants in our cases hints at a potential cooperative role in cancer pathogenesis. Further studies are warranted to elucidate the interplay between BRCA1/2 and DICER1 variants and their implications for cancer predisposition and treatment in pediatric patients. [ABSTRACT FROM AUTHOR]

The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties. The mechanisms underlying MDMA's entactogenic properties of sociability and interpersonal closeness are not known but release and involvement of oxytocin, a peptide thought by some to be involved in social bonding, has been suggested. Adverse effects of MDMA are mostly transient; acute multiorgan adverse effects occurring during raves or crowded dance gatherings include dehydration, hyperthermia, seizures, rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. Deaths following MDMA taken by itself are rare compared to fatalities following coadministration with other drugs. A recent FDA-approved phase 3 clinical trial of MDMA for post-traumatic stress disorder (PTSD) led to the conclusion that MDMA-assisted therapy represents a potential breakthrough treatment meriting expedited clinical evaluation. Despite the ongoing deliberations by the FDA and EMA for approval of MDMA treatment of PTSD, the Australian Therapeutic Goods Administration (TGA) recently announced that after an evaluation of the therapeutic value, benefits, and risks of MDMA, it will permit its prescribing for the treatment of PTSD. Further examples of regulatory relaxation toward MDMA-assisted psychotherapy are underway. These include the FDA's recently approved clinical trial to assess MDMA's efficacy in the treatment of "asociality" in patients with schizophrenia and an open trial of MDMA treatment for alcohol-use disorder which showed decreased alcohol consumption. There are also ongoing studies on the little understood startle response, anxiety associated with life-threatening illness, and social anxiety in autistic adults. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial diseases (MDs) are systemic disorders that can affect multiple organs. Renal manifestations, including renal tubular acidosis, are common because kidneys are particularly vulnerable to energy deprivation. Treatment of MDs is often complex and electrolyte replacement can be difficult especially in pediatric patients, because large and repeated amounts of oral supplements are needed but are not well tolerated. Case presentation: We describe the case of a girl affected by Kearns-Sayre disease with severe renal tubular acidosis. The management of her metabolic acidosis was challenging because she showed persistent low levels of serum bicarbonates despite a progressive incrementation of oral bicarbonates. Furthermore, as a result to the ingestion of large amounts of alkali, the girl developed an aversion to oral supplementation. After positioning a percutaneous gastrostomy (PEG) and starting enteral administration of bicarbonates (with daily boluses and continuous nocturnal infusion), she finally obtained an adequate electrolyte control, with a significant increase in her quality of life. Conclusions: In MDs, the combination of nocturnal continuous enteral administration of alkali plus diurnal boluses may represent a valid solution to correct metabolic acidosis. It can also result in an improved patients' quality of life, particularly in pediatric settings, where compliance to oral therapy is often lacking due to the large and repeated amounts of unpalatable bicarbonates solutions required. [ABSTRACT FROM AUTHOR]

With technological advancements, much data is being captured by sensors, smartphones, wearable devices, and so forth. These vast datasets are stored in data centres and utilized to forge data‐driven models for the condition monitoring of infrastructures and systems through future data mining tasks. However, these datasets often surpass the processing capabilities of traditional information systems and methodologies due to their significant size. Additionally, not all samples within these datasets contribute valuable information during the model training phase, leading to inefficiencies. The processing and training of Machine Learning algorithms become time‐consuming, and storing all the data demands excessive space, contributing to the Big Data challenge. In this paper, we propose two novel techniques to reduce large time‐series datasets into more compact versions without undermining the predictive performance of the resulting models. These methods also aim to decrease the time required for training the models and the storage space needed for the condensed datasets. We evaluated our techniques on five public datasets, employing three Machine Learning algorithms: Holt‐Winters, SARIMA, and LSTM. The outcomes indicate that for most of the datasets examined, our techniques maintain, and in several instances enhance, the forecasting accuracy of the models. Moreover, we significantly reduced the time required to train the Machine Learning algorithms employed. [ABSTRACT FROM AUTHOR]

Low‐cost sensing and the Internet of Things (IoT), present new possibilities for unconventional monitoring of environmental parameters. This paper describes a series of intersecting networks of particulate matter sensors that were deployed across the Birmingham conurbation for a 12‐month period. The networks consisted of a combination of commercially available sensors and University developed sensors. Data from these networks were assimilated with data from a third‐party Zephyr deployment, along with the DEFRA AURN network, which was hosted on an open‐source online platform. This nesting of sensor networks allowed for new insights into sensor performance, including the accuracy of a large network to detect regional concentrations and the number of sensors needed for effective monitoring beyond indicative measurements. After comprehensive data validation steps, the sensors were shown to perform well during co‐location with reference instrumentation (exhibiting slopes of 0.74–1.3). The sensors demonstrated good capability of detecting temporal patterns of regional PM2.5 with the mean of the entire sensor network recording an annual mean PM2.5 concentration within 0.2 μgm−3 of the regulatory network annual mean observation. Network‐derived statistics for estimating urban background concentrations compared to a reference site increase in‐line with the number of sensors available, however when assessing this for near‐source concentrations the importance of sensor location rather than the number of sensors is highlighted. Overall, the network provided novel insights into local concentrations, detecting similar hotspots to those identified by a high‐resolution model. The increased spatial coverage afforded by the sensor network has the potential to support higher resolution evaluation of models and provide unprecedented spatial evidence for air pollution management interventions. [ABSTRACT FROM AUTHOR]

[Display omitted] Dielectric effects and the coupled electrostatics between the nanoconfined and the internal/external aqueous media contribute to the observed deviations of chemistry within the nanoconfined environment when compared with unconfined systems. A systematic understanding has remained elusive, especially with respect to background salt concentration and boundary condition effects like the nanopore surface chemistry and the reference state used to calculate free energies. We utilize molecular dynamics simulations along with thermodynamic integration to determine the free energy difference associated with acid-base chemistry in 2 nm and 4 nm slit pores open to a bulk-like reservoir. pK a increases are predicted when confining acetic acid, formic acid, and bicarbonate in the slits at infinite dilution conditions. We find that confinement weakens the acids, and the modulation of outer pore surface dipole magnitudes can tune the pK a shift values, suggesting that purely "intrinsic" electrostatic effect on confinement may not exist. At sufficiently high salt concentrations, the dielectric/electrostatic effects on pK a values diminish due to charge screening effects. These discoveries enable future modifications of nanopore chemistries to achieve desirable properties for industrial applications. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the effects of different waterlogging duration imposed at the V2 leaf stage and assess the impact of waterlogging on maize growth during the recovery period, identify susceptible and tolerant lines and traits conferring tolerance to waterlogging at the early seedling stage. Methods: The study was arranged in a Split-plot RCBD and replicated three times. Intercharacter and waterlogging durations to maize growth parameters were correlated to determine the degree of the linear relationship using Pearson's product moments correlation and simple linear regression analysis. Result: The result shows that the different waterlogging durations negatively influenced the maize growth parameters regarding plant height and root length. These parameters became shorter and did not recover after waterlogging stress was removed. Therefore, plant height and root length are traits sensitive to waterlogging stress. The USM Var 10, BRK and T. Monkayo obtained a high degree of leaf greenness, heaviest shoot and root dry matter compared to other evaluated maize lines. Maize with greener leaves, taller plant height, longer root length and high total dry matter accumulation could be a good criterion in selecting a parent material in the maize waterlogging breeding program. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples. Electrochemical methods, including microfluidic devices and biosensors, can obtain robust results that reduce time, cost, and assay complexity. This comprehensive review will explore specific studies, methodologies, and detection limits and contribute to the depth of the discussion, making it a valuable resource for researchers and clinicians interested in lung cancer diagnosis. [ABSTRACT FROM AUTHOR]

In the field of atmospheric ionic thrusters, the objective of this work is to evaluate the possibility of an alternative ionic emitter to the traditional thin wire emitter, in order to overcome the technical issues of the EHD technology related to the fragility of the wires and to make it more suitable to applications outside the laboratory. For the presented experiments, emitters in the form of metallic blades have been produced. These were tested while varying the geometric parameters of both the emitters themselves and of the thruster configuration. Through this measurement campaign, the electrical characteristics, as well as the feasibility and the performances of the new proposed solutions have been evaluated and compared with wire emitters. Results indicate that the blade emitters can work as alternative emitters, however the performance of the present prototypes does not reach that of wire emitters and therefore further research is needed in order to make them a valid alternative. [ABSTRACT FROM AUTHOR]

Background: Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. Objective s : To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. Animals: Nineteen euthyroid client‐owned dogs hospitalized for acute illness at a veterinary teaching hospital. Methods: Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. Results: tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03‐0.65] vs 0.11 ng/mL [range (0.05‐0.26)], mean difference = 0.09 ng/mL; P =.03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. Conclusions and Clinical Relevance: In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient with medulloblastoma (MB) who carried biallelic pathogenic MUTYH germline variants. The MUTYH gene is involved in DNA repair and is associated with a type of adenomatous polyposis affecting the colon and duodenum. While there is speculation about an increased risk of other cancers, such as ovarian, endometrial, and breast cancers, the connection remains unclear. The case report highlights the importance of considering MUTYH in the context of MB and related conditions and the need for further research to understand the genetic factors contributing to this cancer. [Extracted from the article]

Acid–base equilibria are generally studied and taught at universities using approaches and techniques that include the use of dyes, spectrophotometry, conductometry, and potentiometry. Instead, voltammetric techniques, although employed for research purposes for acid–base investigations, have rarely been included in electrochemical curricula. In this article, we highlight the potential of microelectrode voltammetry in studying acid–base equilibria, their kinetics, and the acid and base content in aqueous solutions by exploiting the hydrogen and oxygen evolution reactions. Microelectrodes are used as they allow the attainment of reproducible and well-defined convergent mass-transport conditions and the achievement of steady-state diffusion regimes in short times. The resulting steady-state limiting current is proportional to bulk concentration, diffusion coefficient, and electrode radius, which is useful for a more precise evaluation of each of latter quantities. Mention is also made on how mathematical treatments and digital simulation procedures can help in the classification and parameterization of the electrode processes involved. Hydrogen and oxygen evolution from neutral and acid or base aqueous solutions. [ABSTRACT FROM AUTHOR]

Background: In dogs, duration of hypothalamic‐pituitary‐adrenal (HPA) axis suppression after systemic glucocorticoid treatment is reported to vary from a few days to up to 7 weeks after glucocorticoid discontinuation. These data are derived mainly from experimental studies in healthy dogs and not from animals with spontaneous disease. Hypothesis and Objective: To determine the timeline for recovery of the HPA axis in a group of ill dogs treated with intermediate‐acting glucocorticoids (IAGCs). Animals: Twenty client‐owned dogs that received IAGC for at least 1 week. Methods: Single‐center prospective observational study. An ACTH stimulation test, endogenous ACTH concentration, serum biochemistry profile, and urinalysis were performed at T0 (2‐6 days after IAGC discontinuation) and then every 2 weeks (eg, T1, T2, T3) until HPA axis recovery was documented (post‐ACTH cortisol concentration > 6 μg/dL). Results: The median time of HPA axis recovery was 3 days (range, 2‐133 days). Eleven of 20 dogs showed recovery of the HPA axis at T0, 6/20 at T1, and 1 dog each at T2, T5, and T9. Dose and duration of treatment were not correlated with timing of HPA axis recovery. Activities of ALT and ALP were significantly correlated with the post‐ACTH cortisol concentration (rs = −0.34, P =.03; rs = −0.31, P =.05). Endogenous ACTH concentration was significantly correlated with pre (r = 0.72; P <.0001) and post‐ACTH cortisol concentrations (r = 0.35; P =.02). The timing of HPA axis recovery of the dogs undergoing an alternate‐day tapering dose was not different compared to dogs that did not (3.5 vs 3 days, P =.89). Conclusion and Clinical Importance: Most dogs experienced HPA axis recovery within a few days after IAGC discontinuation. However, 2/20 dogs required >8 weeks. [ABSTRACT FROM AUTHOR]

Strawberries are very perishable fruits due to their high metabolic rates and susceptibility to mechanical injuries and infections, which limits their shelf life and generates many post-harvest losses. This study aimed to improve strawberries quality and shelf life by using bioactive films containing sophorolipid and fructooligosaccharides, which present great antimicrobial activity and prebiotic properties, respectively. Sophorolipids were produced by fermentation with Starmerella bombicola using glucose and oleic acid as substrates, and fructooligosaccharides were produced by Bacillus subtilis natto using sucrose as substrate. The films were characterized and their functionality on fresh strawberries was evaluated by physicochemical and microbiological parameters. According to the results, the addition of sophorolipids and fructooligosaccharides reduced the tensile strength of the films, increasing their flexibility by 10 times. Films presented thickness values ranging from 153 to 160 µm. The use of multifunctional films as strawberries coating resulted in a reduction of 41,40% in weight loss of fruits, keeping the pH and anthocyanin content stable over the storage time. In addition, a slowing down of coated strawberries ripening was observed. Interestingly, the coatings were also effective in controlling mold and yeast growth for 15 days, preserving strawberries fresh for a longer period. Taken together, these results showed that the multifunctional bioactive coating containing sophorolipid and fructooligosaccharides could extend the shelf life, add nutritional value, and maintain the microbiological quality attributes of highly perishable fruits such as strawberries. [ABSTRACT FROM AUTHOR]

In many regions of Europe, large wild herbivores alter forest community composition through their foraging preferences, hinder the forest's natural adaptive responses to climate change, and reduce ecosystem resilience. We investigated a widespread European forest type, a mixed forest dominated by Picea abies, which has recently experienced an unprecedented level of disturbance across the continent. Using the forest landscape model iLand, we investigated the combined effect of climate change and herbivory on forest structure, composition, and carbon and identified conditions leading to ecosystem transitions on a 300‐year timescale. Eight climate change scenarios, driven by Representative Concentration Pathways 4.5 and 8.5, combined with three levels of regeneration browsing, were tested. We found that the persistence of the current level of browsing pressure impedes adaptive changes in community composition and sustains the presence of the vulnerable yet less palatable P. abies. These development trajectories were tortuous, characterized by a high disturbance intensity. On the contrary, reduced herbivory initiated a transformation towards the naturally dominant broadleaved species that was associated with an increased forest carbon and a considerably reduced disturbance. The conditions of RCP4.5 combined with high and moderate browsing levels preserved the forest within its reference range of variability, defining the actual boundaries of resilience. The remaining combinations of browsing and climate change led to ecosystem transitions. Under RCP4.5 with browsing effects excluded, the new equilibrium conditions were achieved within 120 years, whereas the stabilization was delayed by 50–100 years under RCP8.5 with higher browsing intensities. We conclude that forests dominated by P. abies are prone to transitions driven by climate change. However, reducing herbivory can set the forest on a stable and predictable trajectory, whereas sustaining the current browsing levels can lead to heightened disturbance activity, extended transition times, and high variability in the target conditions. [ABSTRACT FROM AUTHOR]

This article examines the extent to which the Italian-Canadian queer writer Monica Meneghetti, in her memoir What the Mouth Wants , challenges and disrupts heteronormative notions of gender and sexuality through the code-switching of food terms in Italian or in a Northern Italian dialect. Code-switching is used primarily to evoke memories of Meneghetti's late mother through the author's favourite dishes, and of the homophobia (or rather biphobia) directed at her by her father, with whom she used to make fresh pasta and cook Italian meals. The memories and flashbacks, interspersed with present-day accounts of the preparation of Italian childhood meals with her polyamorous family, allow the memoir's protagonist to build a new sense of family: a queer Italian-Canadian family. Drawing on feminist and queer food studies, the article reveals that Meneghetti uses code-switching to signal point of view and to construct the memoir's characters and plot, as code-switched food items are also linked to the notion of memory and to what it means to write the memoir. [ABSTRACT FROM AUTHOR]

Background: Dogs with eunatremic, eukalemic hypoadrenocorticism (EEH) typically show signs of chronic gastrointestinal disease (CGD). Previous glucocorticoid administration (PGA) can give false‐positive results on the ACTH stimulation test (ACTHst). Hypothesis/Objectives: To determine the prevalence of EEH in dogs with signs of CGD, and to identify clinical and clinicopathological features for EEH and PGA. Animals: One hundred twelve dogs with CGD (101 non‐PGA and 11 PGA), 20 dogs with EEH. Methods: Multicenter prospective cohort study. Basal serum cortisol (BSC) concentration was measured in dogs with signs of CGD. When BSC was <2 μg/dL and in PGA dogs, ACTHst plus measurement of endogenous ACTH (eACTH) were performed. Records of dogs with EEH from 2009 to 2021 were reviewed. Results: The BSC concentration was <2 μg/dL in 48/101 (47.5%) non‐PGA and in 9/11 (82%) PGA dogs. EEH was diagnosed in 1/112 dog (prevalence 0.9%; 95% CI, 0.1%‐4.8%); the ACTHst provided false‐positive results in 2/11 PGA dogs. PGA dogs showed lower C‐reactive protein‐to‐haptoglobin ratio (median 0.01, range 0.003‐0.08; P =.01), and higher haptoglobin (140, 26‐285 mg/dL; P =.002) than non‐PGA dogs (0.04, 0.007‐1.5; 38.5, 1‐246 mg/dL, respectively). eACTH was higher (P =.03) in EEH (396, 5‐>1250 pg/mL) than in non‐PGA dogs (13.5, 7.3‐46.6 pg/mL). Cortisol‐to‐ACTH ratio was lower (P <.0001 and P =.01, respectively) in EEH (0.002, 0.0002‐0.2) than in non‐PGA (0.1, 0.02‐0.2) and PGA dogs (0.1, 0.02‐0.2). Conclusions and Clinical Importance: The prevalence of EEH in dogs with signs of CGD was lower than previously reported. The clinical and clinicopathological features herein identified could increase the index of suspicion for EEH or PGA in dogs with an unclear history of glucocorticoid administration. [ABSTRACT FROM AUTHOR]

At the beginning of the COVID-19 outbreak (end 2019 − 2020), therapeutic treatments based on approved drugs have been the fastest approaches to combat the new coronavirus pandemic. Nowadays several vaccines are available. However, the worldwide vaccination program is going to take a long time and its success will depend on the vaccine public's acceptance. Therefore, outside of vaccination, the repurposing of existing antiviral, anti-inflammatory and other types of drugs, have been considered an alternative medical strategy for the COVI-19 infection. Due to the broad clinical potential of the drugs, but also to their possible side effects, analytical methods are needed to monitor the drug concentrations in biological fluids and pharmaceutical products. This review deals with analytical methods developed in the period 2015 - July 2021 to detect potential drugs that, according to a literature survey, have been taken into consideration for the treatment of COVID-19. The drugs considered here have been selected on the basis of the number of articles published in the period January 2020-July 2021, using the combination of the keywords: COVID-19 and drugs or SARS-CoV-2 and drugs. A section is also devoted to monoclonal antibodies. Over the period considered, the analytical methods have been employed in a variety of real samples, such as body fluids (plasma, blood and urine), pharmaceutical products, environmental matrices and food. [ABSTRACT FROM AUTHOR]

MRGPRX2, a novel Gaq‐coupled human mast cell receptor, mediates non‐immune adverse reactions without the involvement of antibody priming. Constitutively expressed by human skin mast cells, MRGPRX2 modulates cell degranulation producing pseudoallergies manifesting as itch, inflammation and pain. The term pseudoallergy is defined in relation to adverse drug reactions in general and immune/non‐immune‐mediated reactions in particular. A list of drugs with MRGPRX2 activity is presented, including a detailed examination of three important and widely used approved therapies: neuromuscular blockers, quinolones and opioids. For the clinician, the significance of MRGPRX2 is considered as an aid in distinguishing and ultimately identifying specific immune and non‐immune inflammatory reactions. Anaphylactoid/anaphylactic reactions, neurogenic inflammation and inflammatory diseases with a clear or strongly suspected association with MRGPRX2 activation are examined. Inflammatory diseases include chronic urticaria, rosacea, atopic dermatitis, allergic contact dermatitis, mastocytosis, allergic asthma, ulcerative colitis and rheumatoid arthritis. MRGPRX2‐ and allergic IgE/FcεRI‐mediated reactions may be clinically similar. Importantly, the usual testing procedures do not distinguish the two mechanisms. Currently, identification of MRGPRX2 activation and diagnosis of pseudoallergic reactions is generally viewed as a process of exclusion once other non‐immune and immune processes, particularly IgE/FcεRI‐mediated degranulation of mast cells, are ruled out. This does not take into account that MRGPRX2 signals via β‐arrestin, which can be utilized to detect MRGPRX2 activation by employing MRGPRX2 transfected cells to assess MRGPRX2 activation via two pathways, the G‐protein‐independent β‐arrestin pathway and the G‐protein‐dependent Ca2+ pathway. Testing procedures, interpretations for distinguishing mechanisms, patient diagnosis, agonist identification and drug safety evaluations are addressed. [ABSTRACT FROM AUTHOR]

The use of natural compounds and, in general, the use of Complementary and Alternative Medicine (CAM), is growing steadily worldwide, both due to commercial pressure and the increasing use of self-medication and the desire to manage one's own personal health and well-being. Patients facing a cancer diagnosis are also strongly pressured to use these compounds, which are often added to standard therapeutic regimens, that should instead be based solely on diagnostic and therapeutic care pathways (DTCP) or evidence-based medicine (EBM). This study presents two clinical cases of cancer patients who presented to the pharmaceutical consultation service (PCD—Pharmacy Clinical Desk) established at the CRO Institute in Aviano, Italy. Both patients were using natural products along with prescribed chemotherapy. In the first case, a 55-year-old woman diagnosed with bilateral breast cancer with bone metastases, who was using natural compounds based on diosmin, escin (or aescin) and resveratrol in combination with ribociclib anticancer therapy, a severe ADR (neutropenia) was identified as a consequence of the drug–natural product interaction. In the second case, following a detailed medication review by the PCD, we avoided taking a therapeutic treatment (with natural compounds) that in itself could potentially render chemotherapy ineffective in a 57-year-old woman with multiple infiltrating ductal carcinoma of the left breast; the patient was planning to take a natural product containing St. John's Wort tincture and lemon balm tincture, in combination with paclitaxel and trastuzumab. In addition, we describe the corrective actions taken, thus outlining the main objectives of the activity of the PCD's pharmacy counseling service: first, to identify, report, and manage adverse drug reactions (ADRs), and second, to identify therapeutic combinations that present potential risks of toxicity or ineffectiveness of the drug therapy itself. [ABSTRACT FROM AUTHOR]

The increasing use of opioids in pregnant women has led to an alarming rise in the number of cases of neonates with drug-induced withdrawal symptoms known as neonatal opioid withdrawal syndrome (NOWS). NOWS is a toxic heterogeneous condition with many neurologic, autonomic, and gastrointestinal symptoms including poor feeding, irritability, tachycardia, hypertension, respiratory defects, tremors, hyperthermia, and weight loss. Paradoxically, for the management of NOWS, low doses of morphine, methadone, or buprenorphine are administered. NOWS is a polygenic disorder supported by studies of genomic variation in opioid-related genes. Single-nucleotide polymorphisms (SNPs) in CYP2B6 are associated with variations in NOWS infant responses to methadone and SNPs in the OPRM1, ABCB1, and COMT genes are associated with need for treatment and length of hospital stay. Epigenetic gene changes showing higher methylation levels in infants and mothers have been associated with more pharmacologic treatment in the case of newborns, and for mothers, longer infant hospital stays. Respiratory disturbances associated with NOWS are not well characterized. Little is known about the effects of opioids on developing neonatal respiratory control and respiratory distress (RD), a potential problem for survival of the neonate. In a rat model to test the effect of maternal opioids on the developing respiratory network and neonatal breathing, maternal-derived methadone increased apneas and lessened RD in neonates at postnatal (P) days P0 and P1. From P3, breathing normalized with age suggesting reorganization of respiratory rhythm-generating circuits at a time when the preBötC becomes the dominant inspiratory rhythm generator. In medullary slices containing the preBötC, maternal opioid treatment plus exposure to exogenous opioids showed respiratory activity was maintained in younger but not older neonates. Thus, maternal opioids blunt centrally controlled respiratory frequency responses to exogenous opioids in an age-dependent manner. In the absence of maternal opioid treatment, exogenous opioids abolished burst frequencies at all ages. Prenatal opioid exposure in children stunts growth rate and development while studies of behavior and cognitive ability reveal poor performances. In adults, high rates of attention deficit disorder, hyperactivity, substance abuse, and poor performances in intelligence and memory tests have been reported. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome. [ABSTRACT FROM AUTHOR]

The foundation and applications of the Barcelona Catania Paris Madrid (BCPM) energy density functional are briefly reviewed. BCPM uses a paradigm more rooted on density functional theory and fits most of its parameters to sophisticated microscopic nuclear matter calculations. Finite nuclei are accounted for by introducing a direct finite range surface term, spin orbit potential, Coulomb interaction and pairing. Applications of this functional to the calculation of finite nuclei properties are presented as well as applications to the description of neutron star physics. The large number of applications discussed are possible because of the local character of the functional that simplifies enormously calculations in finite nuclei. [ABSTRACT FROM AUTHOR]

Thermoelectric materials that can work at operating temperatures of T ≥ 900 K are highly desirable since the key thermoelectric factors of most thermoelectric materials degrade at high temperatures. In this work, we investigate the high temperature thermoelectric performance of EuFeO3 using a combination of first-principles methods and semi-classical Boltzmann transport theory. High temperature thermoelectric performance is achieved owing to the presence of corrugated flatbands in the valence band region and extremely flatbands in the conduction band region. The lowest energetic structure of EuFeO3 lies within a G-type antiferromagnetic configuration, and the effect of compressive and tensile strains (−7% to +7%) along the (a, b) axes on thermoelectric performance is systematically analyzed. An extremely high value of the Seebeck coefficient (more than 1000 μV/K) is consistently recorded in the high temperature region between 900 K and 1400 K in this material. Furthermore, electrical conductivities and power factors are high and electronic thermal conductivities are low in the considered range of temperatures. The calculated theoretical minimum lattice conductivity is small, estimated at around 1.47–1.54 W m−1 K−1. A compressive strain of −3% is revealed to be the optimum level of strain for enhancing the key thermoelectric factors. Overall, p-type doping shows better thermoelectric performance than n-type doping in EuFeO3. [ABSTRACT FROM AUTHOR]

The list of drugs patients may be exposed to during the perioperative and postoperative periods is potentially extensive. It includes induction agents, neuromuscular blocking drugs (NMBDs), opioids, antibiotics, sugammadex, colloids, local anesthetics, polypeptides, antifibrinolytic agents, heparin and related anticoagulants, blue dyes, chlorhexidine, and a range of other agents depending on several factors related to individual patients' clinical condition and progress in the postoperative recovery period. To avoid poor or ultrarapid metabolizers to a particular drug (for example tramadol and codeine) or possible adverse drug reactions (ADRs), some drugs may need to be avoided during or after surgery. This will be the case for patients with a history of anaphylaxis or other adverse events/intolerances to a known drug. Other drugs may be ceased for a period before surgery, e.g., anticoagulants that increase the chance of bleeding; diuretics for patients with acute renal failure; antihypertensives relative to kidney injury after major vascular surgery; and serotonergic drugs that together with some opioids may rarely induce serotonin toxicity. Studies of germline variations shown by genotyping and phenotyping to identify a predisposition of genetic factors to ADRs offer an increasingly important approach to individualize drug therapy. Studies of associations of human leukocyte antigen (HLA) genes with some serious delayed immune-mediated reactions are ongoing and variations of drug-metabolizing cytochrome CYP450 enzymes, P-glycoprotein, and catechol-O-methyltransferase show promise for the assessment of ADRs and non-responses to drugs, particularly opioids and other analgesics. Surveys of ADRs from an increasing number of institutions often cover small numbers of patients, are retrospective in nature, fail to clearly identify culprit drugs, and do not adequately distinguish immune-mediated from non-immune-mediated anaphylactoid reactions. From the many surveys undertaken, the large list of agents identified during and after anesthesia and surgery are examined for their ADR involvement. Drugs are classified into those most often involved, (NMBD and antibiotics); drugs that are becoming more frequently implicated, namely antibiotics (particularly teicoplanin), and blue dyes; those becoming less frequently involved; and drugs more rarely involved in perioperative, and postoperative adverse reactions but still important and necessary to keep in mind for the occasional potential sensitive patient. Clinicians should be aware of the similarities between drug-induced true allergic type I IgE/FcεRI- and pseudoallergic MRGPRX2-mediated ADRs, the clinical features of each, and their distinguishing characteristics. Procedures for identifying MRGPRX2 agonists and diagnosing and distinguishing pseudoallergic from allergic reaction mechanisms are discussed. [ABSTRACT FROM AUTHOR]

• TyG and HOMA-IR displayed poor agreement; • TyG is weak to moderately correlated with HOMA-IR and other glycemic markers; • TyG is better than HOMA-IR for metabolic syndrome prediction. • Individuals with discordant TyG and HOMA-IR have different cardiometabolic profile. Insulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR). A cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35–74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson's r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Coheńs kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations. TyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR. [ABSTRACT FROM AUTHOR]

The statistical modelling of weather regimes encompasses the definition of a framework involving a dimensionality reduction step to reduce the highly sparse feature space of weather anomaly maps, and unsupervised learning techniques to correctly categorize regimes. Across the literature's methodology, the two stages stick to a recurrent scheme: Empirical Orthogonal Functions or Principal Component Analysis are used to assess the former; a standard K‐Means clustering algorithm maps each datapoint to the closest‐matching regime. However, such a combination has to cope with an overall reduction in the modelling accuracy. In our study, we re‐think both the two steps in favour of a more dynamic methodology which we apply to the last 42‐years winters' geopotential anomaly maps in the North Atlantic‐European zone. The dimensionality reduction is tackled by means of Variational Autoencoders, leading to better compressed feature spaces, enhancing the datapoints separability. Finally, we employ two probabilistic clustering methods based on Gaussian and Dirichlet Process mixture models, enabling a more faithful recognition of weather regimes, and allowing to reproduce their dynamics and transitions. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to provide empirical evidence on the link between intellectual capital and a firm's ability to attract funding and financing in Italian companies. Design/methodology/approach: Data from 125 Italian companies was collected through an online survey and analysed using structural equation modelling (PLS-SEM). Findings: Results show that structural capital has a positive, direct impact on both human and relational capital. At the same time, relational capital is the only intellectual capital component that has a positive, direct impact on a firm's ability to attract funding and financing. Finally, we found that a firm's ability to attract funding and financing impacts both innovation and financial performance. Originality/value: This novel study is among the first to provide empirical evidence of how human, relational and structural capital interact with each other and enhance a firm's ability to attract funding and financing. [ABSTRACT FROM AUTHOR]

Insights into the pathophysiology of many non-immune-mediated drug reactions referred to as toxicities, sensitivities, intolerances, or pseudoallergies have resulted from research identifying the mastocyte-related G-protein-coupled receptor (GPCR) member X2 (MRGPRX2), a human mast cell receptor mediating adverse reactions without the involvement of antibody priming. Opioid-induced degranulation of mast cells, particularly morphine, provoking release of histamine and other preformed mediators and causing hemodynamic and cutaneous changes seen as flushing, headache and wheal and flare reactions in the skin, is an example of results of MRGPRX2 activation. Opioids including morphine, codeine, dextromethorphan and metazocine as well as endogenous prodynorphin opioid peptides activate MRGPRX2 at concentrations causing mast cell degranulation. Unlike the canonical opioid receptors, MRGPRX2 shows stereochemical recognition preference for dextro rather than levo opioid enantiomers. Opioid analgesic drugs (OADs) display a range of histamine-releasing potencies from the strong releaser morphine to doubtful releasers like hydromorphone and the non-releaser fentanyl. Whether there is a correlation between histamine release by individual OADs, MRGPRX2 activation, and presence or absence of adverse cutaneous effects is not known. To investigate the question, ongoing research with recently pursued methodologies and strategies employing basophil and mast cell tests resulting from MRGPRX2 insights should help to elucidate whether or not an opioid's histamine-releasing potency, and its property of provoking an adverse reaction, are each a reflection of its activation of MRGPRX2. [ABSTRACT FROM AUTHOR]

Clinical hematology and tissue histoarchitecture are prognostic indicators of pathological conditions in fish. Using Oreochromis niloticus, a 12-week feeding experiment assessed the hematology and histopathology of ammonia-exposed tissues of gills, kidney and liver. Four treatments were used in the experiment. Fish in the control group was fed the practical diet (T1), while others received diet supplemented with Ipomoea batatas in powder (T2), hot water extract (T3), and crude extract (T4). Hematological profiling was conducted for 12 weeks. Results indicated significant differences at week 6 in neutrophils and lymphocytes, at week 8 in erythrocytes, lymphocytes, eosinophils, and platelets, and at week 12 in hemoglobin (P<0.05). Liver of T1 and T4 illustrated histoarchitecture at normal limits, while erythrocyte infiltration and vacuolation of hepatocytes were observed in T2 and T3. All groups fed I. batatas-supplemented diets showed beneficial effect on the kidney as evidenced by notable decrease in the melanomacrophages. Gill tissues displayed no prominent signs of improvement against widespread infiltration of inflammatory cells in both primary and secondary lamella. The results of the present study demonstrated that incorporation of crude extracts of I. batatas can boost early enhancement of lymphocyte and neutrophil production and improve ammonia-induced kidney and liver histopathology. [ABSTRACT FROM AUTHOR]

The holotype of Odontophrynus americanus collected by Alcide d'Orbigny in northern Patagonia, Argentina differs morphologically from the tetraploid frogs repeatedly assigned to this species and that are distributed from central Argentina and Uruguay to the north to Brazil and Paraguay (probably also Bolivia). Surprisingly, the external characteristics of the holotype match with the morphology of the adult syntype and specimens currently referred to as Odontophrynus occidentalis distributed in central, western, and southern Argentina. On the basis of resemblance in position, number, size, and shape of the glandular warts, we propose that O. americanus should be considered a senior synonym of O. occidentalis. Consequently, we realize that the tetraploid frogs currently called O. americanus were all too often misidentified under this name. After reviewing all the available names applicable to this tetraploid species, we recognize Hyperoodon asper described by Rodolfo A. Philippi as valid, resurrecting this nominal species within the genus Odontophrynus, with the designation of a neotype from Montevideo, Uruguay. We also propose that Ceratophrys argentina Philippi is a nomen dubium. To update the taxonomy of the genus Odontophrynus, we provide partial chresonymies, morphologic diagnoses, cytogenetic and bioacoustic characters, and geographic distribution maps for both O. americanus and O. asper. [ABSTRACT FROM AUTHOR]

Haemonchus contortus is the most pathogenic parasite for sheep. The objective was to evaluate immunomodulation of the probiotic Saccharomyces boulardii in sheep experimentally infected with H. contortus. Twenty‐four sheep were divided into three groups: one infected with 500 H. contortus larvae/day for 26 days and supplemented with S. boulardii (40 ml with 1 × 108 CFU/ml/day); a control group only infected with H. contortus but not supplemented; and a naïve group that never came into contact with either parasites or S. boulardii. To assess the humoral immune response, production of specific serum IgG anti‐somatic H. contortus antigen was evaluated through indirect ELISA. To assess the cellular immune response, cell populations and cytokine (IL‐4, IL‐5 and IL‐10) production were evaluated through flow cytometry. For parasitological analyses, the counts of eggs per gram of faeces (EPG) and larvae per faecal culture were assessed. At all the study points, the concentration of IgG anti‐H. contortus was higher (p <.05) in the S. boulardii group than in the other groups. The cell analysis revealed that there were significantly higher numbers (p <.05) of cells expressing MHC‐II and significantly higher numbers (p <.05) of eosinophils in the mucosa in the S. boulardii group. Significant expression of IL‐10 was observed only in the control infected group. There were significant reductions (p <.05) in EPG and larval counts in the S. boulardii supplemented group. These results show that S. boulardii supplementation modulated the immune response against H. contortus, thereby reducing its infection. [ABSTRACT FROM AUTHOR]

Among health care professionals, dentists are more prone to infection due to their direct contact with blood and saliva. This study highlights the level of compliance with infection control measures among dental students; and linked this to their knowledge and attitudes regarding infection control measures and proper vaccinations. The study is a multi-centre analytical cross-sectional survey. The sample size was 969 clinical years' students from governmental and private dental colleges in Sudan and Saudi Arabia. A pre-coded, pre-tested, and anonymous questionnaire consisted of seven categories of knowledge, attitude, awareness, and practices, including 40 questions, was answered. The study has linked knowledge, attitude, and practice in dental clinics with possible COVID-19 transmission in dental clinics. The results showed that the use of some Personal Protective Equipment was low in Sudan and moderate in Saudi Arabia (statistically significant, p < 0.001). Moderate percentage of Hepatitis B vaccination status, with low percentage of Post HBV serology, was reported (p < 0.001). The percentages of major causes of percutaneous and/or eye exposure/injury, for examples, were as follows: anesthesia (33.3–62.7%, p 0.006) and suture needle (17.5–39.4%, p 0.037). In conclusion, dental students in the present study had good knowledge and positive attitudes regarding infection control in general, but showed moderate compliance with the recommended infection control guidelines. [ABSTRACT FROM AUTHOR]

In this study a novel procedure is presented for an efficient development of predictive models of road pavement asphalt concretes mechanical characteristics and volumetric properties, using shallow artificial neural networks. The problems of properly assessing the actual generalization feature of a model and avoiding the effects induced by a fixed training-test data split are addressed. Since machine learning models require a careful definition of the network hyperparameters, a Bayesian approach is presented to set the optimal model configuration. The case study covered a set of 92 asphalt concrete specimens for thin wearing layers. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic pushed the demand for readily available monitoring tools, leading to the development of electrochemical point-of-care devices. This work presents an electrochemical capillary-driven immunoassay (eCaDI) device based on polyethylene terephthalate (PET) and adhesive films featuring a screen-printed carbon electrode (SPCE) for the detection of SARS-CoV-2 nucleocapsid (N) protein in clinical samples. The SPCE was modified with protein A and capture antibodies (Ab 1) to ensure biomolecule immobilization and enhance sensitivity to detect N protein. The eCaDI automates an enzyme-linked immunosorbent assay (ELISA) through sequential reagent delivery, allowing for one-step sample addition. This process involves capturing the N protein by Ab 1 , followed by the automated delivery of HRP-labelled antibody and 3,3',5,5'-tetramethylbenzidine (TMB) followed by electrochemical detection through TMB reduction. The SPCEs are sensitive and selective for SARS-CoV-2 N protein and stable for four weeks. Inactivated virus was used to determine a limit of detection (LOD) of 627 PFU/mL. The results obtained through immunoassay on eCADI were consistent with those of the RT-PCR method, showing a coefficient of determination (R2) of 0.816 for 27 nasal swab samples from SARS-CoV-2 infected individuals. The developed eCADI is an alternative to conventional ELISA, given the device's low cost (less than $1), low consumption of samples and reagents, low waste generation, and short analysis time (5 min). Moreover, the immunoassay has shown potential for diagnosing COVID-19 in decentralized areas. [Display omitted] [ABSTRACT FROM AUTHOR]

Diffuse midline glioma (DMG) is a heterogeneous group of aggressive pediatric brain tumors with a fatal prognosis. The biological hallmark in the major part of the cases is H3K27 alteration. Prognosis remains poor, with median survival ranging from 9 to 12 months from diagnosis. Clinical and radiological prognostic factors only partially change the progression-free survival but they do not improve the overall survival. Despite efforts, there is currently no curative therapy for DMG. Radiotherapy remains the standard treatment with only transitory benefits. No chemotherapeutic regimens were found to significantly improve the prognosis. In the new era of a deeper integration between histological and molecular findings, potential new approaches are currently under investigation. The entire international scientific community is trying to target DMG on different aspects. The therapeutic strategies involve targeting epigenetic alterations, such as methylation and acetylation status, as well as identifying new molecular pathways that regulate oncogenic proliferation; immunotherapy approaches too are an interesting point of research in the oncology field, and the possibility of driving the immune system against tumor cells has currently been evaluated in several clinical trials, with promising preliminary results. Moreover, thanks to nanotechnology amelioration, the development of innovative delivery approaches to overcross a hostile tumor microenvironment and an almost intact blood–brain barrier could potentially change tumor responses to different treatments. In this review, we provide a comprehensive overview of available and potential new treatments that are worldwide under investigation, with the intent that patient- and tumor-specific treatment could change the biological inauspicious history of this disease. [ABSTRACT FROM AUTHOR]

Opioid-induced respiratory depression (OIRD), the primary cause of opioid-induced death, is the neural depression of respiratory drive which, together with a decreased level of consciousness and obstructive sleep apnea, cause ventilatory insufficiency. Variability of responses to opioids and individual differences in physiological and neurological states (e.g., anesthesia, sleep-disordered breathing, concurrent drug administration) add to the risk. Multiple sites can independently exert a depressive effect on breathing, making it unclear which sites are necessary for the induction of OIRD. The generator of inspiratory rhythm is the preBötzinger complex (preBötC) in the ventrolateral medulla. Other important brainstem respiratory centres include the pontine Kölliker-Fuse and adjacent parabrachial nuclei (KF/PBN) in the dorsal lateral pons, and the dorsal respiratory group in the medulla. Deletion of μ opioid receptors from neurons showed that the preBötC and KF/PBN contribute to OIRD with the KF as a respiratory modulator and the preBötC as inspiratory rhythm generator. Glutamatergic neurons expressing NK-1R and somatostatin involved in the autonomic function of breathing, and modulatory signal pathways involving GIRK and KCNQ potassium channels, remain poorly understood. Reversal of OIRD has relied heavily on naloxone which also reverses analgesia but mismatches between the half-lives of naloxone and opioids can make it difficult to clinically safely avoid OIRD. Maternal opioid use, which is rising, increases apneas and destabilizes neonatal breathing but opioid effects on maternal and neonatal respiratory circuits in neonatal abstinence syndrome (NAS) are not well understood. Methadone, administered to alleviate symptoms of NAS in humans, desensitizes rats to RD. [ABSTRACT FROM AUTHOR]

Simple Summary: Ewing sarcoma is a rare and aggressive tumor of childhood and adolescence. Over the years, different prognostic factors have been explored to stratify high-risk patients. The roles of C-reactive protein (CRP) and serum lactate dehydrogenase (LDH) as potential new prognostic factors would be a useful and simple for risk stratification, but they have rarely been investigated. In our work, we analyze the role of LDH and CRP as prognostic factors in a population of pediatric and adolescent patients affected by Ewing sarcoma. Our study confirms the potential prognostic role of LDH at diagnosis as an independent prognostic factor. LDH evaluation is not expensive, and it can be beneficial for developing countries where diagnostic and staging resources in the pediatric oncology field are poor. Background: Ewing sarcoma (ES) is a rare and aggressive pediatric cancer. Numerous studies have attempted to identify new prognostic biomarkers. The predictive value of serum LDH and CRP has not been clearly described, to date. Methods: The objective of our retrospective study was to investigate the prognostic value of LDH and CRP levels and their association with overall survival in a series of ES patients. Results: Between 2004 and 2019, 89 ES patients were included. In a univariable analysis, high levels of LDH and CRP were associated with the worst prognosis. In a multivariable analysis, only higher LDH values remained associated with a lower survival. The high-LDH-level group experienced all 21 deaths registered in our population (24%) and about 90% of disease progressions. The 5-year overall survival was 66.4% in the high-LDH-level group, while no deaths were observed in the low-LDH-level group. The 5-year progression-free survival was 57.9% in the high-LDH-level group versus 80.4% in the low-LDH-level group. Conclusions: In our study, LDH levels at diagnosis were strongly correlated with the prognosis, and they might be considered a prognostic factor in Ewing sarcoma. The LDH value, along with its very low cost and its reproducibility in almost all centers, make it suitable as a potential prognostic biomarker in clinical practice. [ABSTRACT FROM AUTHOR]

This letter responds to a previous publication about a rare case of trigeminal chronic motor denervation caused by a cerebellar peduncle pilocytic astrocytoma in a child. The authors describe a similar case of a female patient who presented with weakness in her right lower limb and later experienced pain and paresthesia on the right side of her face. Magnetic resonance imaging revealed a tumor in the right middle cerebellar peduncle, extending into the pons, midbrain, and cerebral peduncle. The patient underwent surgery to remove the tumor, which was a pilocytic astrocytoma, and experienced improvement in her motor impairment but worsening trigeminal neuralgia. The authors emphasize the importance of investigating the involvement of the trigeminal nerve in patients with tumors in the middle cerebellar peduncle and highlight the potential impact on quality of life. [Extracted from the article]

In nature, confrontations between conspecifics are recurrent and related, in general, due to the lack of resources such as food and territory. Adequate defence against a conspecific aggressor is essential for the individual's survival and the group integrity. However, repeated social defeat is a significant stressor promoting several behavioural changes, including social defence per se. What would be the neural basis of these behavioural changes? To build new hypotheses about this, we here investigate the effects of repeated social stress on the neural circuitry underlying motivated social defence behaviour in male mice. We observed that animals re-exposed to the aggressor three times spent more time in passive defence during the last exposure than in the first one. These animals also show less activation of the amygdalar and hypothalamic nuclei related to the processing of conspecific cues. In turn, we found no changes in the activation of the hypothalamic dorsal pre-mammillary nucleus (PMD) that is essential for passive defence. Therefore, our data suggest that the balance between the activity of circuits related to conspecific processing and the PMD determines the pattern of social defence behaviour. Changes in this balance may be the basis of the adaptations in social defence after repeated social defeat. [ABSTRACT FROM AUTHOR]

Background: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical. Case presentation: We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities. Conclusions: In addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures. Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications. [ABSTRACT FROM AUTHOR]

Experiments were undertaken to identify the nature of a previously identified inhibitor of PAF-induced platelet aggregation (PA) in human saliva. Human saliva fractionated by preparative thin layer chromatography (TLC) yielded a fraction that co-migrated with fatty acids (FAs) and inhibited PAF-induced aggregation of platelets. Synthetic FAs tested for their capacities to inhibit 0.1 nM PAF-induced PA showed that only the cis-unsaturated compounds were inhibitory with activities of some of the polyunsaturated FAs (PUFA) reaching almost 100% at 20 μM. Eicosapentanoic acid (EPA) and 8,11,14-eicosatrienoic acid also deaggregated the PAF-induced aggregates. With the exception of oleic acid (OLA), cis-monounsaturated FAs, and elaidic acid, the trans isomer of OLA, were poor inhibitors. In a direct comparison with other platelet agonists, ADP, thrombin, and ionophore A23187, the active saliva fraction and selected individual FAs inhibited, to greater or lesser extent, PA induced by each of the agonists. EPA, OLA, linoleic acid (LNA), and the active saliva fraction were potent inhibitors of ADP-induced PA, EPA completely inhibited thrombin-induced PA and the saliva fraction showed only weak – moderate inhibitory activity to both thrombin- and ionophore A23187-induced PA. Other reports of endogenous PAF inhibitors in mammalian tissues are compared to the present results. PAF can trigger and amplify inflammatory cascades suggesting a possible modulation role for cis-unsaturated FAs in some diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Embryonal tumors include a heterogeneous group of tumors that need multimodal and multidisciplinary treatments in which craniospinal irradiation (CSI) plays a major role, with a known impact on the acute toxicity and future quality of life of patients. Neutropenia represents one of the most common acute hematological side effects and is responsible for infections and treatment delays that can affect the effectiveness of therapy. To better describe hematological acute toxicity during proton beam radiation treatment, we retrospectively examined 20 subsequent pediatric patients affected by high-risk embryonal tumors subjected to CSI with dual-phase proton therapy after a chemotherapy regimen. Our data suggest that the dual-phase technique is safe and feasible in this setting of pediatric patients with a significant baseline hematological toxicity. Despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with proton therapy, and, therefore, no treatment was discontinued or delayed. Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed. [ABSTRACT FROM AUTHOR]

Graphene-based materials are among the most innovative and promising materials for the development of high-performance sensing devices, mainly due to the large surface area and the possibility to modify their reactivity by suitable functionalization. In the field of sensing applications, the peculiarities of innovative materials can be exploited only if chemical and physical properties are fully understood and correlated with each other. To this aim, in this work, graphene oxide (GO) and ethanol-treated GO (GOEt) were investigated from chemical and structural points of view. Electrical characterization was performed by depositing GO and GOEt between two electrodes by dielectrophoresis. All the investigations were repeated on GO materials after thermal treatment in a low temperature range (60 °C-300 °C). Furthermore, the electrical conductivity of GO was investigated by changing the temperature and the environment (air or N2) during the characterization: an increase in the conductivity of the as-deposited GO was observed when the device is cooled down and this effect is reversible with the temperature. GOEt and the thermally treated GO and GOEt show an opposite trend, confirming the key role of the oxygen functionalities in the conduction mechanisms and, therefore, in the conductivity of the GO layers. [ABSTRACT FROM AUTHOR]

In-memory computing (IMC) has the potential of accelerating data-intensive computing tasks, such as inference and training of neural networks, by the matrix vector multiplication (MVM) in the crosspoint array. As the array size increases, however, a significant problem arises due to the parasitic IR drop at row and column lines. Understanding and compensating IR drop is essential to enable high-density accelerators of MVM. This work presents an analytical model for the IR drop and a numerical algorithm capable of accelerating the nodal analysis of crosspoint arrays up to five orders of magnitude with respect to SPICE analysis. The numerical algorithm is used to study the impact of array size, data density, device/wire resistance, and nonlinearity on the IR drop and the related loss of accuracy in IMC. We also derive two simple compensation schemes and an architectural solution for the mitigation of IR drop that are able to increase the accuracy of neural networks from 59% up to 96.6%, compared to an ideal accuracy of 97%. [ABSTRACT FROM AUTHOR]

Background: Basal serum cortisol (BSC) ≥2 μg/dL (>55 nmol/L) has high sensitivity but low specificity for hypoadrenocorticism (HA). Objective: To determine whether the urinary corticoid:creatinine ratio (UCCR) can be used to differentiate dogs with HA from healthy dogs and those with diseases mimicking HA (DMHA). Animals: Nineteen healthy dogs, 18 dogs with DMHA, and 10 dogs with HA. Methods: Retrospective study. The UCCR was determined on urine samples from healthy dogs, dogs with DMHA, and dogs with HA. The diagnostic performance of the UCCR was assessed based on receiver operating characteristics (ROC) curves, calculating the area under the ROC curve. Results: The UCCR was significantly lower in dogs with HA (0.65 × 10−6; range, 0.33‐1.22 × 10−6) as compared to healthy dogs (3.38 × 10−6; range, 1.11‐17.32 × 10−6) and those with DMHA (10.28 × 10−6; range, 2.46‐78.65 × 10−6) (P <.0001). There was no overlap between dogs with HA and dogs with DMHA. In contrast, 1 healthy dog had a UCCR value in the range of dogs with HA. The area under the ROC curve was 0.99. A UCCR cut‐off value of <1.4 yielded 100% sensitivity and 97.3% specificity in diagnosing HA. Conclusions and Clinical Importance: The UCCR seems to be a valuable and reliable screening test for HA in dogs. The greatest advantage of this test is the need for only a single urine sample. [ABSTRACT FROM AUTHOR]