Search

BackgroundIntegration of community health workers/promotores in community-based participatory research is an efficient strategy to advance research and health initiatives. We build on the principles of the interactive and contextual model of community-university collaboration for research and action, the public health critical race framework, and the situated learning theory to propose the community-driven research framework for the development of culturally appropriate research methods training and integration of promotores as co-researchers.ObjectivesTo present the community-driven research framework as a model that trains and integrates promotores in research methodologies.Application of the Community-Driven Research Framework: By showcasing three case studies (March 2019 to December 2021) we describe the promotores' levels of involvement through the various research stages highlighting the effectiveness of the community-driven research framework.ConclusionsThe community-driven research framework fills a gap in the literature by providing a process through which researchers can engage in a culturally relevant learning process that allows entry to the community, fostering trust, and initiating a mutual collaboration that is embedded within the local context and needs of the community. The implementation of the community-driven research framework has implications for the development of culturally sensitive community partnerships as well as for designing research that is centered around the cultural and social context of the community.

Abstract Objective Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case–control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. Methods We enrolled consecutive patients aged ≥55 years presenting with late‐onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age‐matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood‐sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi‐squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. Results We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3–20.6, p = 0.02). Significance The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. Plain Language Summary Late‐onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Abstract Aims We report the results of a real‐world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life. Methods and results We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ‐5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e′ (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High‐Sensitivity Kit determined elevated interleukin‐6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period. Conclusions This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs.

Anthemis L. 1753 is a species-rich genus of Asteraceae. It includes species of economic value as ornamental, edible and medicinal plants. We report here the complete chloroplast genome of Anthemis cretica subsp. calabrica (Arcang.) R. Fern. 1975, the first chloroplast genome of any Anthemis species. For the scope, we have used long reads obtained with Oxford Nanopore technology. The assembled plastome is 149,509 bp long and is subdivided in a large single-copy region (LSC, 82,317 bp), a small single-copy region (SSC, 18,212 bp) and two inverted repeat regions (IR: 24,490 bp). It comprehends 136 predicted genes, of which 92 protein-coding genes, 35 tRNAs, and 8 rRNAs. The overall GC content is 37.54%. The position of A. cretica subsp. calabrica in the phylogenetic tree is congruent with those of previous analyses based on a few chloroplast or nuclear regions.

Background: Long-haul truck drivers (LHTD) experience disproportionately greater chronic disease risk, which may be influenced by both occupational and lifestyle factors. This study aimed to explore the multilevel factors associated with LHTD's diet and physical activity (PA). Methods: Thirty in-depth interviews were conducted with LHTD in the Southern California border region. Interview questions captured occupational and lifestyle factors relating to PA and diet at multiple levels and were analyzed using thematic analysis. Results: Emergent themes relating to both diet and PA included time constraints, attitudes and perceived beliefs, and accessibility of environments to engage in PA and healthy eating. Themes specific to PA were weather conditions and flatbed job duties. Themes specific to diet included access to refrigerators/microwaves and social interactions. Conclusion: Findings from this study can inform the development of tailored, multi-level interventions to encourage PA and healthy dietary behaviors among LHTD.

Abstract The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.

Many heritage buildings from ancient Rome are being refurbished based on their original plan’s structure. One of them is the piscina mirabilis located nearby in Naples, which was a cistern used by the Romans to collect drinkable water for the navy waiting in the port of Misenum. The piscina mirabilis has similar architectural characteristics to a “cathedral”; however, its current precarious architectural state is the result of high levels of humidity that have caused the proliferation of mold on its vertical and horizontal surfaces over the centuries. Acoustic measurements were conducted inside the piscina mirabilis, highlighting an existing condition of the room being very reverberant, not suitable for occasional speech and conversations. The design proposed by the authors involves some mitigation solutions for the acoustics, mainly focused on controlling the low–medium frequencies and the realization of a restoration project consisting of a raised timber-floored walkway that runs along the perimeter walls, with the addition of water covering the existing floor as a natural element dominating the room volume, which represents the primary function of the building in antiquity. A waterfall was designed to be on the northern side wall. Acoustic studies were an important part of the refurbishment strategy, and a mitigation solution was devised to control medium–low frequencies by using inflated balloons of different sizes that were suspended from the ceiling vaults instead of widely used acoustic panels. The proposed strategy lowered the reverberation time by 3–4 s to accommodate a minimal level of conversational understanding. Such a solution is appropriate for this heritage building as well as other future conservation projects.

Abstract The worldline formalism is a useful scheme in Quantum Field Theory which has also become a powerful tool for numerical computations. It is based on the first quantisation of a point-particle whose transition amplitudes correspond to the heat-kernel of the operator of quantum fluctuations of the field theory. However, to study a quantum field theory in a bounded manifold one needs to restrict the path integration domain of the point-particle to a specific subset of worldlines enclosed by those boundaries. In the present article it is shown how to implement this restriction for the case of a spinor field in a two-dimensional curved half-plane under MIT bag boundary conditions, and compute the first few heat-kernel coefficients as a verification of the proposed construction. This construction admits several generalisations.

Abstract Mutations in CHCHD10, a mitochondrial protein with undefined functions, are associated with autosomal dominant mitochondrial diseases. Chchd10 knock-in mice harboring a heterozygous S55L mutation (equivalent to human pathogenic S59L) develop a fatal mitochondrial cardiomyopathy caused by CHCHD10 aggregation and proteotoxic mitochondrial integrated stress response (mtISR). In mutant hearts, mtISR is accompanied by a metabolic rewiring characterized by increased reliance on glycolysis rather than fatty acid oxidation. To counteract this metabolic rewiring, heterozygous S55L mice were subjected to chronic high-fat diet (HFD) to decrease insulin sensitivity and glucose uptake and enhance fatty acid utilization in the heart. HFD ameliorated the ventricular dysfunction of mutant hearts and significantly extended the survival of mutant female mice affected by severe pregnancy-induced cardiomyopathy. Gene expression profiles confirmed that HFD increased fatty acid utilization and ameliorated cardiomyopathy markers. Importantly, HFD also decreased accumulation of aggregated CHCHD10 in the S55L heart, suggesting activation of quality control mechanisms. Overall, our findings indicate that metabolic therapy can be effective in mitochondrial cardiomyopathies associated with proteotoxic stress.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAFV600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.

Lucia Festino*, Alessio Fabozzi*, Anna Manzo, Valentina Gambardella, Erika Martinelli, Teresa Troiani, Ferdinando De Vita, Michele Orditura, Fortunato Ciardiello, Floriana Morgillo Division of Medical Oncology, Department of clinical and experimental medicine and surgery "F. Magrassi e A. Lanzara", Second University of Naples, Napoli, Italy*These authors contributed equally to this work Abstract: The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I–II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients. Keywords: colorectal cancer, angiogenesis, regorafenib

Background The percentage of women

In aqueous environment amphiphilic molecules organize themselves into supramolecular structures deeply affecting the chemo-physical properties. Supramolecular assemby is also crucial in the pharmaceutical development of bioactive lipophilic molecules whose attitude to self-aggregate is a recognized factor affecting the in vivo pharmacokinetic, but can also play a crucial role in the interaction with the biological targets in in vitro tests. In aqueous solution, amphiphilic drugs exist in a complex equilibrium involving free monomers, oligomers and larger supramolecular aggregates held together by noncovalent bonds. In this review we focus our attention on the dual effect of drugs self-assembly, which can both reduce the availability of active compounds and create multivalent scaffolds, potentially improving binding affinity and avidity to cellular targets. We examine the effect of aggregation on different classes of amphiphatic molecules with significant biological activities, such as immunomodulatory, anti-tumor, antiviral, and antibiotic.Our purpose is to provide a comprehensive overview of how supramolecular chemistry influences the pharmacological and biological responses of amphiphilic molecules, emphasizing the need to consider these effects in early-stage drug development and in vitro testing. By elucidating these phenomena, this review aims to offer insights into optimizing drug design and formulation to overcome challenges posed by self-aggregation.

Chloroplast genomes (plastomes) represent a very important source of valuable information for phylogenetic and biogeographic reconstructions. The use of short reads (as those produced from Illumina sequencing), along with de novo read assembly, has been considered the “gold standard” for plastome reconstruction. However, short reads often cannot reconstruct long repetitive regions in chloroplast genomes. Long Nanopore (ONT) reads can help bridging long repetitive regions but are by far more error-prone than those produced by Illumina sequencing. Verbesina is the largest genus of tribe Heliantheae (Asteraceae) and includes species of economic importance as ornamental or as invasive weeds. However, no complete chloroplast genomes have been published yet for the genus. We utilized Illumina and Nanopore sequencing data and different assembly strategies to reconstruct the plastome of Verbesina alternifolia and evaluated the usefulness of the Nanopore assemblies. The two plastome sequence assemblages, one obtained with the Nanopore sequencing and the other inferred with Illumina reads, were identical, except for missing bases in homonucleotide regions. The best-assembled plastome of V. alternifolia was 152,050 bp in length and contained 80, 29, and four unique protein-coding genes, tRNAs, and rRNAs, respectively. When used as reference for mapping Illumina reads, all plastomes performed similarly. In a phylogenetic analysis including 28 other plastomes from closely related taxa (from the Heliantheae alliance), the two Verbesina chloroplast genomes grouped together and were nested among the other members of the tribe Heliantheae s.str. Our study highlights the usefulness of the Nanopore technology for assembling rapidly and cost-effectively chloroplast genomes, especially in taxonomic groups with paucity of publicly available plastomes.

Designer fuel fraud consists in the smuggling of modified diesel blends as engine lubricant oils and their illegal trade avoiding payment of the excise duty applied to energy products. The fraudulent mixture contains regular diesel fuel plus a heavier hydrocarbon fraction, originating from waste automotive lubricant or cheap, residual base oils.Raman spectroscopy was tested as a rapid in-situ screening method to separate regular diesel fuel samples from those suspected to contain a heavier component, and thus demanding a more extensive characterization. The Raman fingerprint region from the screened sample is matched to purposely created spectral libraries of compliant and non-compliant diesel fuels using the instrumental search algorithm. Overall, 177 compliant fuel samples and 28 non-compliant samples (all designer fuels with a confirmed heavier fraction and/or anomalous distillation parameters) were measured. The designer fuels were all positively identified, with ∼18 % false positives.Subsequently, the Raman data-set was studied by Principal Component Analysis (PCA) and then classified as either compliant or non-compliant using Linear Discriminant Analysis (LDA). PCA using up to three principal components for data visualization shows only an incipient separation but still a partial overlap between compliant and non-compliant samples. LDA, on the opposite, performed superiorly in the binary classification task, with no false negatives and less than 4 % false positives.

The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

En este artículo, la robustez de la bien conocida técnica de par calculado es mejorada en dos aspectos: por un lado, la ley de control de bucle interno se hace depender exclusivamente de señales generadas por el usuario cuya precisión ya no se ve afectada por ruido o errores numéricos; por otro lado, la ley de control de bucle externo se hace depender de posiciones medibles y velocidades estimadas por un observador, lo que reduce el costo de implementación. Tanto el controlador como el observador son estructuras no lineales diseñadas por medio de desigualdades matriciales lineales que resultan de reescribir en forma convexa el sistema del error de seguimiento y el sistema del error de observación por medio de una factorización recientemente aparecida en la literatura para luego aplicar el método directo de Lyapunov. La propuesta de diseño es puesta a prueba en diversos sistemas Lagrange-Euler donde las ventajas en comparación con el par calculado tradicional pueden ser apreciadas tanto en simulación como en tiempo real.

International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea for cancer treatment. The impact of multidisciplinary care (MDC) on patient outcomes is not univocal, while the effective functioning of the MDT depends on many factors. This review presents the available MDT literature with an emphasis on the key factors that characterize high-quality patient care in lung cancer. The study was conducted with a bibliographic search using different electronic databases (PubMed Central, Scopus, Google Scholar, and Google) referring to multidisciplinary cancer care settings. Many key elements appear consolidated, while others emerge as prevalent and actual, especially those related to visible barriers which work across geographic, organizational, and disciplinary boundaries. MDTs must be sustained by strategic management, structured within the entity, and cannot be managed as a separate care process. Furthermore, they need to coordinate with other teams (within and outside the organization) and join with the broad range of services delivered by multiple providers at various points of the cancer journey or within the system, with the vision of integrated care.

A queueing system with the discipline of flexible limited sharing of the server is considered. This discipline assumes the admission, for a simultaneous service, of only a finite number of orders, as well as the use of a reduced service rate when the bandwidth required by the admitted orders is less than the total bandwidth of the server. The orders arrive following a batch-marked Markov arrival process, which is a generalization of the well-known $ MAP $ (Markov arrival process) to the cases of heterogeneous orders and batch arrivals. The orders of different types have different preemptive priorities. The possibility of an increase or a decrease in order priority during the service is suggested to be an effective mechanism to prevent long processing orders from being pushed out of service by just-arrived higher-priority orders. Under a fixed priority scheme and a mechanism of dynamic change of the priorities, the stationary analysis of this queueing system is implemented by considering a suitable multidimensional continuous-time Markov chain with a generator that has an upper Hessenberg structure. The possibility of the optimal restriction on the number of simultaneously serviced orders is numerically demonstrated.

Abstract Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1, differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPβ and NFIC. As a result, silencing of C/EBPβ and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPβ and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.

Abstract Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.