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Nitrates (NO3‐) are crucial in agricultural practices and the food industry, but their excessive presence in water can lead to adverse health effects. Their leaching into water sources necessitates regular monitoring. This study introduces a novel bimodal electrochemical (EC)/photoelectrochemical (PEC) sensor, utilizing copper‐modified graphitic carbon nitride (Cu/g‐C3N4), designed for precise nitrate determination. The structural morphology and chemical composition of the Cu/g‐C3N4 nanocomposite were meticulously examined using Transmission Electron Microscopy (TEM) and Fourier‐transform infrared spectroscopy (FTIR). The optimization of copper loading in g‐C3N4 was conducted, and the electrochemical behavior and light irradiation interaction of various Cu/g‐C3N4 nanocomposites were systematically studied. The investigation revealed that 20 % Cu/g‐C3N4 represented the optimal doping ratio, establishing the most promising candidate for NO3‐. Nitrates were consistently measured using both EC and PEC techniques, yielding Limits of Detection (LoD) of 3.75 and 9.60 ppm, respectively. The sensor's robust performance was further demonstrated in the presence of possible interferents. The proposed sensors were also successfully used to detect NO3‐ in commercial water. This bimodal sensor presents a promising approach for accurate nitrate determination, attesting to its potential for effective cross‐validation. [ABSTRACT FROM AUTHOR]

Introduction: Risk‐reducing salpingo‐oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer. Despite the solid recommendation, women frequently refuse surgery and uptake rates reported in the literature are diverse. This study analyses the uptake rate of RRSO in BRCA 1/2 PV‐carriers referred to a specialised referral centre for first counselling and investigate personal factors linked to the decision. Methods: This is a single‐centre prospective study of BRCA1/2 PV‐carriers referred for the first counselling to IRCCS Fondazione San Gerardo de' Tintori (Monza, Italy) between January 2010 and May 2023. Depending on individual characteristics, women were either proposed RRSO or surveillance, consisting of transvaginal ultrasound and CA125 measurement twice per year according to Regional guidelines. Women within the centre have access to a clinical psychologist, a nutritional consult and treatment of menopausal atrophy with diode vaginal laser. The primary endpoint of the study was the uptake rate of RRSO. The secondary objective was to evaluate the main reasons for refusing surgery. Results: Among the 287 women included, surgery was proposed to 205 women either at first counselling or during surveillance and was accepted by 197, with an uptake rate of 96.1%. 17.25% of women met the psychologist before or after surgery. The main reasons for refusing RRSO were fear of iatrogenic menopause and childbearing desire. Conclusion: This study shows a high uptake rate of RRSO in BRCA PV‐carriers. We believe that the presence of a dedicated outpatient clinic with a multidisciplinary team contributes decisively to our results. Gynaecologic surveillance, as though not beneficial in terms of oncological prevention, may play a significant role in encouraging women with BRCA PV to opt for risk‐reducing surgery. [ABSTRACT FROM AUTHOR]

Cranial ultrasound reliably diagnoses many neonatal brain disorders. Adding Doppler imaging expands the spectrum by providing information on the status of the vasculature and haemodynamics that may guide further diagnostic and clinical management. Doppler imaging may identify neonates with congenital or acquired vascular abnormalities such as perinatal stroke, sinuvenous thrombosis, vein of Galen malformation, dural sinus malformation, sinus pericranii, and developmental venous anomaly. These entities may need further investigation with complementary imaging modalities such as magnetic resonance imaging and magnetic resonance angiography, or conventional angiography. This review aims to help clinicians to improve their Doppler sonography knowledge and skills in order to use this helpful tool in neonates with neurological symptoms or suspected cerebral vascular abnormalities admitted to the neonatal intensive care unit. [ABSTRACT FROM AUTHOR]

Background: Trazodone, an antidepressant drug is also largely used in several medical contexts. Insomnia, behavioral disorders, and anxiety may be underlying symptoms for prescribing trazodone. This cross‐sectional study aims to identify reasons for trazodone prescription, assess the efficacy, as well as identify any related side effects in older persons living in long term care facilities (LTCFs). Methods: Older adults aged ≥ 60 years, at risk of or affected with Covid‐19 and enrolled in the GeroCovid Observational study from LTCFs, and using trazodone were included. A structured questionnaire was administered to treating physicians regarding reasons for trazodone prescription, discontinuation, possible adverse events and benefits. Results: Thirty‐seven out 74 LTCFs participating in both the GeroCovid and GeroCovid Vax studies completed the questionnaire regarding trazodone use. Of the 427 participants included in this study analysis, we found that 43% had diagnoses of dementia and depression, 33% had dementia, no behavioral and psychological symptoms of dementia (BPSD) and no depression, 14% had dementia with BPSD and no depression, and < 11% had only depression. The main reasons for trazodone prescription included agitation, insomnia, depression and anxiety. Trazodone use was reported as partially or totally effective in more than 90% of participants using the drug. Falls were the most frequent adverse event (30% of participants). Conclusions: Our data suggest that trazodone behaves as an eclectic antidepressant that, in the clinical practice, may also be used for BPSD and insomnia, especially in older people with dementia. [ABSTRACT FROM AUTHOR]

Neonatal ventriculomegaly often, but not always, follows intraventricular haemorrhage in infants born preterm. Serial cranial ultrasonography (CUS) is a very useful tool to evaluate the mechanism behind ventricular dilatation, to differentiate several types of cerebrospinal fluid retention, and to guide treatment. This review examines neonatal ventriculomegaly and its definition, pathophysiology, treatment, and prognosis from the perspective of CUS assessment. It also outlines the consensus statements formulated by the EurUS.Brain group, which are based on rounds of expert opinions on neonatal ventriculomegaly management, detailing the need and timing of ventricular access device placement, in the context of posthaemorrhagic ventricular dilation. The pathophysiology of neonatal ventriculomegaly is more complex than previously considered. CUS is a valuable, non‐invasive tool to determine pathophysiology, intervention thresholds, and prognosis in neonates with ventriculomegaly. Given new insights into the existence of glymphatics and water circulation in the cerebrum, further research in that area may bring new treatment options. What this paper adds: Cranial ultrasonography has a significant role in better understanding the complex pathophysiology of neonatal ventriculomegaly.The latest research suggests that treating posthaemorrhagic ventricular dilation in its early stages has several advantages.Proper definition, management, and a follow‐up plan are essential because they can impact the infant and their family, health care providers, educational systems, and society. [ABSTRACT FROM AUTHOR]

The thalamic nuclei develop before a viable preterm age. GABAergic neuronal migration is especially active in the third trimester. Thalamic axons meet cortical axons during subplate activation and create the definitive cortical plate in the second and third trimesters. Default higher‐order cortical driver connections to the thalamus are then replaced by the maturing sensory networks, in a process that is driven by first‐order thalamic neurons. Surface electroencephalographic activity, generated first in the subplate and later in the cortical plate, gradually show oscillations based on the interaction of the cortex with thalamus, which is controlled by the thalamic reticular nucleus. In viable newborn infants, in addition to sensorimotor networks, the thalamus already contributes to visual, auditory, and pain processing, and to arousal and sleep. Isolated thalamic lesions may present as clinical seizures. In addition to asphyxia and stroke, infection and network injury are also common. Cranial ultrasound can be used to classify neonatal thalamic injuries based on functional parcelling of the mature thalamus. We provide ample illustration and a detailed description of the impact of neonatal focal thalamic injury on neurological development, and discuss the potential for neuroprotection based on thalamocortical plasticity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro‐regenerative local milieu and re‐establish proper oligodendrocyte functions may be beneficial. Experimental Approach: Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein‐coupled receptor 17 (GPR17) and of cysteinyl‐leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. Key Results: Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro‐regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex‐based difference in the protective activity of MTK. Conclusions and Implications: Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti‐asthmatic drug, may be a promising sex‐specific strategy for personalized ALS treatment. [ABSTRACT FROM AUTHOR]

Pulmonary valve replacement (PVR) consists of substituting a patient's original valve with a prosthetic one, primarily addressing pulmonary valve insufficiency, which is crucially relevant in Tetralogy of Fallot repairment. While extensive clinical and computational literature on aortic and mitral valve replacements is available, PVR's post‐procedural haemodynamics in the pulmonary artery and the impact of prosthetic valve dynamics remain significantly understudied. Addressing this gap, we introduce a reduced Fluid–Structure Interaction (rFSI) model, applied for the first time to the pulmonary valve. This model couples a three‐dimensional computational representation of pulmonary artery haemodynamics with a one‐degree‐of‐freedom model to account for valve structural mechanics. Through this approach, we analyse patient‐specific haemodynamics pre and post PVR. Patient‐specific geometries, reconstructed from CT scans, are virtually equipped with a template valve geometry. Boundary conditions for the model are established using a lumped‐parameter model, fine‐tuned based on clinical patient data. Our model accurately reproduces patient‐specific haemodynamic changes across different scenarios: pre‐PVR, six months post‐PVR, and a follow‐up condition after a decade. It effectively demonstrates the impact of valve implantation on sustaining the diastolic pressure gradient across the valve. The numerical results indicate that our valve model is able to reproduce overall physiological and/or pathological conditions, as preliminary assessed on two different patients. This promising approach provides insights into post‐PVR haemodynamics and prosthetic valve effects, shedding light on potential implications for patient‐specific outcomes. [ABSTRACT FROM AUTHOR]

Urban environment design profoundly influences citizens' health and well‐being. Despite the aim of urban regeneration initiatives to enhance community well‐being and social connections, they often struggle to ensure a balance of power among stakeholders, effectively involve citizens, and accurately assess subjective urban experiences. New methodological approaches in community‐based participatory research (CBPR) are advocated to facilitate interactions among social actors and overcome the digital versus real dichotomy. This article introduces the Experiential Environmental Impact Assessment (exp‐EIA) method as a novel research and intervention tool to address these challenges. Grounded in psychology, exp‐EIA aims to integrate emotional, cognitive, and community identity dimensions to capture the nuanced experiences of urban environments. Through digital data collection and visualization tools, exp‐EIA could facilitate participatory decision‐making processes across various stages of urban regeneration projects. Furthermore, its adaptability enables significant integration with existing participatory methods, fostering inclusive engagement and innovative design solutions. The theoretical framework of exp‐EIA, its application in CBPR, and its potential to bridge the gap between technological innovation and citizen engagement in urban regeneration processes are discussed. A blended case study conducted in the metropolitan area of Milan (Italy) is presented, highlighting a promising pathway towards more inclusive and effective approaches to community revitalization. [ABSTRACT FROM AUTHOR]

Organic waste valorization is one of the principal goals of the circular economy. Bioprocesses offer a promising approach to achieve this goal by employing microorganisms to convert organic feedstocks into high value products through their metabolic activities. In this study, a fermentation process for yeast cultivation and extracellular lipase production was developed by utilizing food waste. Lipases are versatile enzymes that can be applied in a wide range of industrial fields, from detergent, leather, and biodiesel production to food and beverage manufacturing. Among several oleaginous yeast species screened, Saitozyma flava was found to exhibit the highest secreted lipase activity on pNP‐butyrate, pNP‐caproate, and pNP‐caprylate. The production medium was composed of molasses, a by‐product of the sugar industry, which provided nutrients for yeast biomass formation. At the same time, waste cooking oil was employed to induce and enhance extracellular lipase production. After 48 h of process, 20 g/L of yeast biomass and 150 mU/mgdw of lipase activity were achieved, with a productivity of 3 mU/mgdw/h. The purified lipase from S. flava showed optimal performances at temperature 28°C and pH 8.0, exhibiting a specific activity of 62 U/mg when using p‐NPC as substrate. [ABSTRACT FROM AUTHOR]

Objective: To investigate cortical microstructural measures from diffusion MRI as "neurodegeneration" markers that could improve prognostic accuracy in mild cognitive impairment (MCI). Methods: The prognostic power of Amyloid/Tau/Neurodegeneration (ATN) biomarkers to predict progression from MCI to AD or non‐AD dementia was investigated. Ninety patients underwent clinical evaluation (follow‐up interval 32 ± 18 months), lumbar puncture, and MRI. Participants were grouped by clinical stage and cerebrospinal fluid Amyloid and Tau status. T1‐structural and diffusion MRI scans were analyzed to calculate diffusion metrics related to cortical columnar structure (AngleR, ParlPD, PerpPD+), cortical mean diffusivity, and fractional anisotropy. Statistical tests were corrected for multiple comparisons. Prognostic power was assessed using receiver operating characteristic (ROC) analysis and related indices. Results: A progressive increase of whole‐brain cortical diffusion values was observed along the AD continuum, with all A+ groups showing significantly higher AngleR than A−T−. Investigating clinical progression to dementia, the AT biomarkers together showed good positive predictive value (with 90.91% of MCI A+T+ converting to dementia) but poor negative predictive value (with 40% of MCI A−T− progressing to a mix of AD and non‐AD dementias). Adding whole‐brain AngleR as an N marker, produced good differentiation between stable and converting MCI A−T− patients (0.8 area under ROC curve) and substantially improved negative predictive value (+21.25%). Interpretation: Results support the clinical utility of cortical microstructure to aid prognosis, especially in A−T− patients. Further work will investigate other complexities of the real‐world clinical setting, including A−T+ groups. Diffusion MRI measures of neurodegeneration may complement fluid AT markers to support clinical decision‐making. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word‐finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face‐recognition deficits (60%). Real‐life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real‐life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights: This project is the first international collaboration and largest reported cohort.Further efforts are warranted for precise nomenclature reflecting neural mechanisms.Our results will serve as a clinical guideline for early and accurate diagnoses. [ABSTRACT FROM AUTHOR]

In the area of security, human cognition remains essential for face recognition despite advancements in technology. Law enforcement agencies (LEAs) are interested in harnessing these abilities, as recognizing people is a fundamental aspect of their work. We conducted two studies to support integrating human face recognition skills into police work. In study 1, we developed the Zurich Face Cognition Test (ZFCT), a self‐assessment tool that reliably measures the face cognition abilities of police officers with authentic police material. Our approach is complementary to the identification of super‐recognizers. In study 2, we evaluated the Holistic Cognitive Interview (HCI), a method successfully applied in the UK to recognize facial composites better. Our results indicate that the HCI provides an effective strategy for police officers to memorize images of unfamiliar faces more effectively, for example, for better recognition of wanted or missing persons. [ABSTRACT FROM AUTHOR]

Background: The growing importance of psychological recovery for patients and their families following intensive care unit (ICU) experiences in recent years cannot be overemphasized. The ICU diary is used to aid patients in reducing the prevalence of post-traumatic stress disorder, anxiety, and depression. The usefulness of maintaining a diary during the grieving process has not yet been thoroughly investigated. Aim: To investigate the role of ICU diaries in the grief process experienced by family members of a person who died in the intensive care unit. Study Design: Nine family members of seven deceased ICU patients with an ICU diary were contacted and interviewed by phone using a semi-structured interview. A qualitative data analysis was performed using thematic synthesis. Setting: Italian general intensive care unit. Findings: Interviewed family members felt that the diary helped them during the grieving process. The return of diaries was desired by family members for support and to remember one's loved one. The diary helped them process their losses in various ways, including signs of evidence of care, emotional involvement, consideration, and coping with grief. Four main themes emerged from the analysis: writing the diary, reading the diary, talking about the diary, and the diary during the grieving process. Conclusions: The overall perception of the ICU diary was positive. The diary mostly helped relatives to "give back something of what we lost". This study also affirms the positive link between ICU diaries and bereavement in Italian ICU. Further studies are required to confirm the usefulness of this tool in the grieving process. Relevance to Clinical Practice: The ICU diary can help patients' family members understand what happened to their loved one and play an important role in the grieving process. The diary served as a valuable source of information that aided in providing bereavement support to the family by helping them to gain a rational and emotional understanding of the patient's death. [ABSTRACT FROM AUTHOR]

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product‐likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product‐likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small‐molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world. [ABSTRACT FROM AUTHOR]

The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild‐type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1‐type cellular and humoral responses, which were primed by high levels of parasite‐specific IFN‐γ, IL‐12, TNF‐α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection. [ABSTRACT FROM AUTHOR]

Background: Chest compression is a lifesaving intervention in out‐of‐hospital cardiac arrest (OHCA), but the optimal metrics to assess its quality have yet to be identified. The objective of this study was to investigate whether a new parameter, that is, the variability of the chest compression‐generated transthoracic impedance (TTI), namely ImpCC, which measures the consistency of the chest compression maneuver, relates to resuscitation outcome. Methods: This multicenter observational, retrospective study included OHCAs with shockable rhythm. ImpCC variability was evaluated with the power spectral density analysis of the TTI. Multivariate regression model was used to examine the impact of ImpCC variability on defibrillation success. Secondary outcome measures were return of spontaneous circulation and survival. Results: Among 835 treated OHCAs, 680 met inclusion criteria and 565 matched long‐term outcomes. ImpCC was significantly higher in patients with unsuccessful defibrillation compared to those with successful defibrillation (p =.0002). Lower ImpCC variability was associated with successful defibrillation with an odds ratio (OR) of 0.993 (95% confidence interval [95% CI], 0.989–0.998, p =.003), while the standard chest compression fraction (CCF) was not associated (OR 1.008 [95 % CI, 0.992–1.026, p =.33]). Neither ImpCC nor CCF was associated with long‐term outcomes. Conclusions: In this population, consistency of chest compression maneuver, measured by variability in TTI, was an independent predictor of defibrillation outcome. ImpCC may be a useful novel metrics for improving quality of care in OHCA. [ABSTRACT FROM AUTHOR]

Continued advancements in environmental DNA (eDNA) research have made it possible to access intraspecific variation from eDNA samples, opening new opportunities to expand non‐invasive genetic studies of wildlife populations. However, the use of eDNA samples for individual genotyping, as typically performed in non‐invasive genetics, still remains elusive. We present successful individual genotyping of eDNA obtained from snow tracks of three large carnivores: brown bear (Ursus arctos), European lynx (Lynx lynx) and wolf (Canis lupus). DNA was extracted using a protocol for isolating water eDNA and genotyped using amplicon sequencing of short tandem repeats (STR), and for brown bear a sex marker, on a high‐throughput sequencing platform. Individual genotypes were obtained for all species, but genotyping performance differed among samples and species. The proportion of samples genotyped to individuals was higher for brown bear (5/7) and wolf (7/10) than for lynx (4/9), and locus genotyping success was greater for brown bear (0.88). The sex marker was typed in six out of seven brown bear samples. Results for three species show that reliable individual genotyping, including sex identification, is now possible from eDNA in snow tracks, underlining its vast potential to complement the non‐invasive genetic methods used for wildlife. To fully leverage the application of snow track eDNA, improved understanding of the ideal species‐ and site‐specific sampling conditions, as well as laboratory methods promoting genotyping success, is needed. This will also inform efforts to retrieve and type nuclear DNA from other eDNA samples, thereby advancing eDNA‐based individual and population‐level studies. [ABSTRACT FROM AUTHOR]

Summary: In this work, we present a mixed‐dimensional mathematical model to obtain the electric potential and current density in direct current simulations when a thin liner is included in the modelled domain. The liner is used in landfill management to prevent leakage of leachate from the waste body into the underground and is made of a highly‐impermeable high‐resistivity plastic material. The electrodes and the liner have diameters and thickness, respectively, that are much smaller than their other dimensions, thus their numerical simulation might be too costly in an equi‐dimensional setting. Our approach is to approximate them as objects of lower dimension and derive the corresponding equations. The obtained mixed‐dimensional model is validated against laboratory experiments of increasing complexity to show the reliability of the proposed mathematical model. Our tests also show that configurations with current and voltage electrodes on either sides of the liner confining the landfill may be effective in detecting damages of the membrane. [ABSTRACT FROM AUTHOR]

Structural neuroplasticity of the hippocampus in the form of neurogenesis and dendritic remodelling underlying morphine tolerance is still less known. Therefore, in this study, we aimed to assess whether unconditioned‐ and conditioned‐morphine tolerance can trigger structural neuroplasticity in the dorsal and ventral parts of the adult male rat hippocampus. Evaluation of the levels of neurogenesis markers (Ki67 and DCX) by immunohistochemistry shows that conditioned morphine tolerance is sufficient to increase the baseline topographic level of hippocampal neurogenesis in adult rats. Dendritic spine visualization by Golgi staining shows that the behavioural testing paradigms themselves are sufficient to trigger the hippocampus subregion‐specific changes in the dendritic remodelling along the apical dendrites of hippocampal CA1 pyramidal neurons and dentate granule cells in adult rats. Quantitative reverse transcription polymerase chain reaction of Bdnf, Trkb, Rac‐1 and RhoA mRNA levels as pro‐plasticity molecules, shows that the conditioned morphine tolerance is effective in changing Bdnf and RhoA mRNA levels in the ventral hippocampus of adult rats. In summary, we demonstrate that the acquisition of morphine tolerance promotes adult neurogenesis, dendritic remodelling and pro‐plasticity molecules such as Bdnf/Trkb in the rat hippocampus. Indeed, the structural neuroplasticity of the hippocampus may underlie the newly formed aberrant memory and could provide the initial basis for understanding the neurobiological mechanisms of morphine‐tolerance plasticity in the hippocampus. [ABSTRACT FROM AUTHOR]

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward‐seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague–Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT‐1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area‐specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC‐NAc‐Hipp circuits, which may modulate rewarding and memory processes. [ABSTRACT FROM AUTHOR]

This article articulates and defends a dissolution of the so‐called repugnant conclusion, which focuses on the notion of life worth living figuring both in Parfit's formulation of the repugnant conclusion and in most responses to such a conclusion. The proposed dissolution demonstrates that the notion of life worth living is plagued by multiple ambiguities and that these ambiguities, in turn, hamper meaningful debate about both the issue of whether the repugnant conclusion can be avoided and the issue of whether the repugnant conclusion is actually repugnant. This result does not exclude that some modified versions of the repugnant conclusion may yield valuable insights about the value of populations and the tenability of different axiological/ethical theories. Still, if the proposed dissolution is correct, then the repugnant conclusion rests on an ill‐defined notion and we lack the information required to assess the merits of the repugnant conclusion. [ABSTRACT FROM AUTHOR]

Introduction: The majority of research conducted into cyberbullying tends to focus on the victims, due to the serious consequences and effects that this crime has on them. However, there is a need to explore, categorize and identify cyberbullies and their characteristics so that inferences and crime links can be made to prevent the crime. The present study aimed to investigate whether the Narrative Action System Model (NASM) could be used to identify and examine the psychological underpinnings of different cyberbully offending styles. Methods: This model proposes four distinct narrative offender styles: the Professional, The Revenger, The Hero and the Victim. A total of 70 cases were analysed using a non‐metric multidimensional scaling procedure (Smallest Space Analysis I). Results: Results produced four types of cyberbully styles, which can be related to the differentiation proposed by the NASM, demonstrating an effective application of the model. The thematic structure of each cyberbully style was discussed. Limitations and implications were provided. [ABSTRACT FROM AUTHOR]

Background: Predominant right temporal atrophy is a radiological sign usually associated with frontotemporal dementia but this sign can also be present in Alzheimer's disease. Given the overlap of clinical symptoms between the two conditions, it is important to know which characteristics allow them to be differentiated. Objectives: To compare clinical, neuropsychological and structural magnetic resonance imaging (MRI) data of subjects with prominent right anterior temporal atrophy, depending on the status of amyloid biomarkers. Methods: Among patients followed in the dementia center of Ospedale Maggiore Policlinico, subjects with right anterior temporal atrophy, defined as grade 3 or 4 on the corresponding visual rating scale, were identified. Only subjects with both an MRI scan and amyloid status available were considered. For selected subjects, data were extracted from clinical and neuropsychological records at initial presentation and at last available follow‐up. Two raters applied a protocol of eight visual rating scales to compare brain atrophy and white matter hyperintensities. Results: Of 497 subjects, 17 fulfilled the inclusion criteria: 7 amyloid‐positive and 10 amyloid‐negative. At initial presentation, executive dysfunction and topographical disorientation were more common in amyloid‐positive patients. At follow‐up, behavioral symptoms, such as social awkwardness and compulsive attitude, were more frequent in the amyloid‐negative patients. Amyloid‐positive patients presented an overall worse neuropsychological performance, especially in the language and visuospatial domain, and had higher scores on the right anterior cingulate visual rating scale. Conclusion: Patients with predominant right temporal atrophy showed clinical, neuropsychological and radiological differences, depending on the status of amyloid biomarkers. [ABSTRACT FROM AUTHOR]

The selective pressure from pathogens on individuals can have direct consequences on reproduction. Genes from the major histocompatibility complex (MHC) are central to the vertebrate adaptive immune system and pathogen resistance. In species with biparental care, each sex has distinct reproductive roles and levels of investment, and due to a trade‐off with immunity, one can expect different selective regimes acting upon the MHC of each parent. Here, we addressed whether couples combine each other's variation at MHC loci to increase their breeding success. Specifically, we used a 23‐year dataset from a barn owl population (Tyto alba) to understand how MHC class Iα and IIβ functional divergence and supertypes of each parent were associated with clutch size and fledging success. We did not detect associations between MHC diversity and supertypes with the clutch size or with the fledging success. In addition, to understand the relative contribution from the MHC of the genetic parents and the social parents, we analyzed the fledging success using only a cross‐fostered dataset. We found several associations of weak‐to‐moderate effect sizes between the father's MHC and fledging success: (i) lower MHC‐Iα divergence in the genetic father increases fledging success, which might improve paternal care during incubation, and (ii) one and two MHC‐IIβ DAB2 supertypes in the social father decrease and increase, respectively, fledging success, which may affect the paternal care after hatching. Furthermore, fledging success increased when both parents did not carry MHC‐IIβ DAB1 supertype 2, which could suggest conditional effects of this supertype. Although our study relied on a substantial dataset, we showed that the associations between MHC diversity and reproductive success remain scarce and of complex interpretation in the barn owl. Moreover, our results highlighted the need to incorporate more than one proxy of reproductive success and several MHC classes to capture more complex associations. [ABSTRACT FROM AUTHOR]

Background: During the pandemic outbreak, helmet continuous positive airway pressure (CPAP) was widely used as respiratory support for COVID‐19 patients, inside and outside of intensive care units. The available literature suggests specific interventions to improve the comfort of patients treated with helmet‐CPAP. Few reports are available on the experiences of patients undergoing this treatment. Aim: This qualitative study aimed to explore the views and recollections of COVID‐19 patients undergoing helmet‐CPAP. Study Design: We conducted semi‐structured interviews with thematic analysis. Participants were recruited from the follow‐up programme for COVID‐19 patients discharged from an Italian general intensive care unit. Participants were interviewed by telephone. Data analysis followed the principles of thematic synthesis approach. Findings: We conducted 29 phone calls in patients eligible for the study. Five participants declared that they did not remember the time spent in hospital on helmet‐CPAP. Twenty‐four patients were then included. Two themes and six subthemes were generated from their interview data: (1) The helmet‐CPAP as a life‐saving treatment (subthemes: recognition of the usefulness of treatment and resilience); (2) the negative feelings related to helmet‐CPAP application (subthemes: communication problems, entrapment, mental confusion, fear of dying). Each patient's experience was unique, but some discomfort elements such as noise, gas flow turbulence, choking sensation and thirst were found to be very common. Conclusions: The application of helmet‐CPAP treatment generated positive and negative memories and feelings in COVID‐19 patients during the pandemic. The patients' experience has provided an overview of the main factors of discomfort. This can be a starting point for taking corrective measures to promote greater helmet tolerance and subsequent treatment success. Relevance to Clinical Practice: This study has provided an insight into the patient's recollections about helmet‐CPAP treatment during a worldwide pandemic. The findings suggested strict applications of interventions aimed to reduce some issues that participants reported, to improve their compliance to treatment. Results from this study could help nurses in understanding the needs of patients treated with helmet‐CPAP and may foster a care focused on patient‐centred outcomes. [ABSTRACT FROM AUTHOR]

The article focuses on real-world effectiveness of an ethnic diet plan for managing gestational diabetes in high-risk ethnic groups. It aims to demonstrate how tailoring dietary interventions based on Mediterranean diet principles can impact maternal and fetal outcomes, as well as insulin therapy requirements, in females with gestational diabetes mellitus (GDM) from diverse ethnic backgrounds attending an Interdisciplinary Diabetes and Pregnancy Center.

TDC are hematopoietic cells that combine dendritic cell (DC) and conventional T‐cell markers and functional properties. They were identified in secondary lymphoid organs (SLOs) of naïve mice as cells expressing CD11c, major histocompatibility molecules (MHC)‐II, and the T‐cell receptor (TCR). Despite thorough characterization, a physiological role for TDC remains to be determined. Unfortunately, using CD11c as a marker for TDC has the caveat of its upregulation on different cells, including T cells, upon activation. Here, we took advantage of Zbtb46‐GFP reporter mice to explore the frequency and localization of TDC in different tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDC sorted from Zbtb46‐GFP mice have a gene signature that is distinct from conventional T cells and DC. In addition, this reporter model allowed for identification of TDC in situ not only in SLOs but also in the liver and lung of naïve mice. Interestingly, we found that TDC numbers in the SLOs increased upon viral infection, suggesting that TDC might play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDC in several pathological contexts, including infection and cancer. [ABSTRACT FROM AUTHOR]

A major challenge in the computational fluid dynamics modeling of the heart function is the simulation of isovolumetric phases when the hemodynamics problem is driven by a prescribed boundary displacement. During such phases, both atrioventricular and semilunar valves are closed: consequently, the ventricular pressure may not be uniquely defined, and spurious oscillations may arise in numerical simulations. These oscillations can strongly affect valve dynamics models driven by the blood flow, making unlikely to recovering physiological dynamics. Hence, prescribed opening and closing times are usually employed, or the isovolumetric phases are neglected altogether. In this article, we propose a suitable modification of the Resistive Immersed Implicit Surface (RIIS) method (Fedele et al., Biomech Model Mechanobiol 2017, 16, 1779–1803) by introducing a reaction term to correctly capture the pressure transients during isovolumetric phases. The method, that we call Augmented RIIS (ARIIS) method, extends the previously proposed ARIS method (This et al., Int J Numer Methods Biomed Eng 2020, 36, e3223) to the case of a mesh which is not body‐fitted to the valves. We test the proposed method on two different benchmark problems, including a new simplified problem that retains all the characteristics of a heart cycle. We apply the ARIIS method to a fluid dynamics simulation of a realistic left heart geometry, and we show that ARIIS allows to correctly simulate isovolumetric phases, differently from standard RIIS method. Finally, we demonstrate that by the new method the cardiac valves can open and close without prescribing any opening/closing times. [ABSTRACT FROM AUTHOR]

Background and Purpose: Psychotic disorders have been reported in long‐term users of synthetic cannabinoids. This study aims at investigating the long‐lasting effects of repeated JWH‐018 exposure. Experimental Approach: Male CD‐1 mice were injected with vehicle, JWH‐018 (6 mg·kg−1), the CB1‐antagonist NESS‐0327 (1 mg·kg−1) or co‐administration of NESS‐0327 and JWH‐018, every day for 7 days. After 15 or 16 days washout, we investigated the effects of JWH‐018 on motor function, memory, social dominance and prepulse inhibition (PPI). We also evaluated glutamate levels in dialysates from dorsal striatum, striatal dopamine content and striatal/hippocampal neuroplasticity focusing on the NMDA receptor complex and the neurotrophin BDNF. These measurements were accompanied by in vitro electrophysiological evaluations in hippocampal preparations. Finally, we investigated the density of CB1 receptors and levels of the endocannabinoid anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG) and their main synthetic and degrading enzymes in the striatum and hippocampus. Key Results: The repeated treatment with JWH‐018 induced psychomotor agitation while reducing social dominance, recognition memory and PPI in mice. JWH‐018 disrupted hippocampal LTP and decreased BDNF expression, reduced the synaptic levels of NMDA receptor subunits and decreased the expression of PSD95. Repeated exposure to JWH‐018, reduced hippocampal CB1 receptor density and induced a long‐term alteration in AEA and 2‐AG levels and their degrading enzymes, FAAH and MAGL, in the striatum. Conclusion and Implications: Our findings suggest that repeated administration of a high dose of JWH‐018 leads to the manifestation of psychotic‐like symptoms accompanied by alterations in neuroplasticity and change in the endocannabinoid system. [ABSTRACT FROM AUTHOR]

Introduction: Non-operative management (NOM) of uncomplicated acute appendicitis is a well-established alternative to upfront surgery. The administration of intravenous broad-spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non-inferiority study was to evaluate both safety and non-inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis. Methods: The study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon's preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30-day appendectomy rate, with a non-inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30-day unplanned emergency department (ED) visits, and length of stay. Results: 30-day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non-inferior to inNOM with a risk difference of—3.80% 97.5% CI (− 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty-six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1–4) days. In the outNOM group, the mean cumulative in-hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001). Conclusions: Outpatient NOM was non-inferior to inpatient NOM with regard to the 30-day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Nanocellulose (NC) is an emerging material in the food sector with several prospective application areas. Three main types of NC exist, i.e. bacterial NC (BNC), nanofibrillated cellulose (NFC), and cellulose nanocrystals (CNC). The biological sources and processing conditions affect several physicochemical parameters of NC. In the present project, a NAM‐based IATA for addressing data gaps in the assessment of potential hazards associated to NC oral exposure was considered. This IATA focused on three main pillars, i.e. (i) assessment of the uptake and potential crossing of the intestinal barrier by NC, (ii) assessment of local effects, including inflammation and genotoxicity, on the gastrointestinal epithelia, and (iii) assessment of any digestion or degradation of NC by the human microbiome. Eight NC samples belonging to the three NC types, plus a comparator in the micro‐range, were selected as study materials and submitted to a thorough physicochemical characterisation. A battery of in vitro tests was used to provide insight into NC hazard and mode of action according to a tiered approach, which lead to selection of three materials belonging to the three main NC types for in depth‐testing. Cell uptake of these materials was demonstrated, and such uptake was greater in a triculture model, which better simulates the barrier properties of the human intestinal epithelium, as compared to Caco‐2 monolayers. Uptake was the greatest in repeated exposure conditions, in which intestinal barrier crossing was demonstrated for CNC. Pro‐inflammatory responses accompanied by massive NC uptake in macrophages, indicative for potential immunotoxicological effects, and barrier function impairment were observed, whereas no indications for genotoxicity were obtained. Finally, no formation of smaller particles following colonic fermentation of NC was observed. For the integration of these results in regulatory hazard assessment of NC after oral exposure, prospective use of NC as novel food or as food additive was considered. [ABSTRACT FROM AUTHOR]

Facing rapid environmental changes and anthropogenic habitat destruction, animal behavioural plasticity becomes an adaptive potential that needs to be considered in conservation strategies along with, for example, genetic diversity. Here, we evaluate to what extent non‐invasive environmental DNA (eDNA) methods may contribute to the assessment of intraspecies behavioural plasticity in terms of foraging behaviour.We analysed DNA metabarcoding data for plant components in the diet of four neighbouring groups of wild vervet monkeys Chlorocebus pygerythrus to identify intergroup variation (IGV). The faecal samples considered for the analyses were limited to the summer season to minimise the impact of seasonality. Each sample was attributed by observation to individuals with known life history data. A plant survey was conducted in each group home range during the study period to account for environmental variation.We observed mixed results when testing whether IGV in plant consumption was greater than intragroup variation, indicating that the influence of social dynamics must be considered. Intragroup variation was positively correlated with group size. We observed IGV in diet composition among all groups as well as in some pairwise comparisons. We found significant dietary differences between two group pairs when considering only adult females. Lastly, we observed IGV in foraging of specific plants that were not explained by their distribution, suggesting behavioural differences in selectivity between groups.Our study system and organism, being a highly social and non‐threatened primate species, with constant gene flow and overlapping territories between groups, provides an ideal model to evaluate the usage of eDNA‐based methods to better understand the impact of social factors on IGV. Our results highlight the need to consider social and demographic factors, the impact of which remains complicated to disentangle from environmental factors. However, we emphasise the great potential for studying social groups using eDNA and that such studies are needed to better understand intraspecific behavioural plasticity in wild populations. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) is a minimally invasive intervention for the treatment of severe aortic valve stenosis. The main cause of failure is the structural deterioration of the implanted prosthetic leaflets, possibly inducing a valvular re‐stenosis 5–10 years after the implantation. Based solely on pre‐implantation data, the aim of this work is to identify fluid‐dynamics and structural indices that may predict the possible valvular deterioration, in order to assist the clinicians in the decision‐making phase and in the intervention design. Patient‐specific, pre‐implantation geometries of the aortic root, the ascending aorta, and the native valvular calcifications were reconstructed from computed tomography images. The stent of the prosthesis was modeled as a hollow cylinder and virtually implanted in the reconstructed domain. The fluid‐structure interaction between the blood flow, the stent, and the residual native tissue surrounding the prosthesis was simulated by a computational solver with suitable boundary conditions. Hemodynamical and structural indicators were analyzed for five different patients that underwent TAVI – three with prosthetic valve degeneration and two without degeneration – and the comparison of the results showed a correlation between the leaflets' structural degeneration and the wall shear stress distribution on the proximal aortic wall. This investigation represents a first step towards computational predictive analysis of TAVI degeneration, based on pre‐implantation data and without requiring additional peri‐operative or follow‐up information. Indeed, being able to identify patients more likely to experience degeneration after TAVI may help to schedule a patient‐specific timing of follow‐up. [ABSTRACT FROM AUTHOR]

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS‐CoV‐2 pandemic. Nirmatrelvir—an orally available inhibitor of the 3‐chymotrypsin‐like cysteine protease—has been shown to reduce the risk of progression to severe COVID‐19. However, the impact of nirmatrelvir treatment on the development of SARS‐CoV‐2‐specific adaptive immune responses is unknown. Here, by using mouse models of SARS‐CoV‐2 infection, we show that nirmatrelvir administration blunts the development of SARS‐CoV‐2‐specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir‐treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals. Synopsis Nirmatrelvir administration to SARS‐CoV‐2‐infected mice blunts the development of SARS‐CoV‐2‐specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir‐treated mice recruited significantly fewer memory T and B cells.Adaptive immune response is impaired across different SARS‐CoV‐2 variants and regardless of the time of treatment.Our results might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals. [ABSTRACT FROM AUTHOR]

A photoelectrochemical sensor composed of a heterojunction between titanium dioxide and gold nanoparticles was fabricated and used for the determination of ciprofloxacin, a widely used, but environmentally toxic third‐generation antibiotic. This material has been extensively characterized from the morphological, electrochemical and photoelectrochemical points of view, comparing it with the respective counterparts. It has been demonstrated that only the presence of the heterojunction allows the detection of ciprofloxacin, thanks to the properties of gold nanoparticles combined with those of titanium dioxide. These increased performances have allowed the detection of the analyte even with low power sources and wavelengths in the visible region, obtaining good detection limits and excellent resistance to possible interferents. Thanks to this, the future implementation of these sensors in integrated circuits for online and onsite analysis is foreseen. [ABSTRACT FROM AUTHOR]

Loneliness is a complex set of aversive feelings that arises when people perceive that their belongingness needs are not being met. Usually, these feelings of loneliness are temporary because people successfully cope with their loneliness by connecting with others. However, for some people, their attempts to cope with loneliness are unsuccessful, and their loneliness becomes chronic, which can have severe consequences for their mental and physical health. Understanding the causes and consequences of loneliness is critical for developing interventions to reduce loneliness, a need made more urgent by the dramatic rise in reported loneliness over the last few decades. In this review, we provide a synthesis of the research on how people cope with loneliness through consumption situations and the extent to which these coping strategies are successful. We also provide a discussion of how the marketplace has responded to the rapidly increasing levels of chronic loneliness worldwide. We conclude with an agenda for future research to answer both basic and applied research questions regarding the causes, consequences, and underlying processes of loneliness. [ABSTRACT FROM AUTHOR]

Introduction: The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. Methods: We performed a kinome‐wide CRISPR/Cas9 knock‐out screen in human induced pluripotent stem cell (iPSC) ‐derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex‐vivo studies. Results: Knock‐down of NIMA‐related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock‐down of nek6 also ameliorated the poly(PR)‐induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53‐related DNA damage. Discussion: We identified NEK6, which regulates poly(PR)‐mediated p53‐related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS. [ABSTRACT FROM AUTHOR]

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia. Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax‐based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here. Results: In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE‐A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event. Conclusions: Real‐life data show that the combination of venetoclax and HMA offers an expectation of remission and long‐term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life. This is an Italian multicentric cohort study evaluating efficacy and safety of venetoclax + hypomethylating agents (HMA) in a real‐life setting of newly diagnosed, relapsed, and refractory patients with acute myeloid leukemia (AML). The data show that the combination of venetoclax and HMA offers an expectation of remission and long‐term survival not only to newly diagnosed but also to relapsed or refractory elderly patients with AML. [ABSTRACT FROM AUTHOR]

We propose a mathematical and numerical model for the simulation of the heart function that couples cardiac electrophysiology, active and passive mechanics and hemodynamics, and includes reduced models for cardiac valves and the circulatory system. Our model accounts for the major feedback effects among the different processes that characterize the heart function, including electro‐mechanical and mechano‐electrical feedback as well as force‐strain and force‐velocity relationships. Moreover, it provides a three‐dimensional representation of both the cardiac muscle and the hemodynamics, coupled in a fluid–structure interaction (FSI) model. By leveraging the multiphysics nature of the problem, we discretize it in time with a segregated electrophysiology‐force generation‐FSI approach, allowing for efficiency and flexibility in the numerical solution. We employ a monolithic approach for the numerical discretization of the FSI problem. We use finite elements for the spatial discretization of partial differential equations. We carry out a numerical simulation on a realistic human left heart model, obtaining results that are qualitatively and quantitatively in agreement with physiological ranges and medical images. [ABSTRACT FROM AUTHOR]