The reliability of Computational Fluid Dynamics (CFD) in reproducing qualitative and quantitative features of loadings exerted by waves on Seawave Slot-cone Generators (SSG) has been investigated via ...17 numerical experiments, conducted with the suite Flow 3D. The geometry of the Wave Energy Converter (WEC), as well as the characteristics of the foreshore in front of it, were identical to those used by the authors in a laboratory study, carried out on a small scale model of a pilot plant to be located along the West Norwegian coasts; the similitude of the layouts allowed an in depth comparison between the results. A good agreement has been generally found between physical and numerical experiments, apart from some aspects of the wave-structure interaction that, however, can be considered secondary for engineering purposes.
OBJECTIVES:To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women.
...MATERIALS AND METHODS:We enrolled asymptomatic women aged ≥25BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer.
RESULTS:A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥50 years of age.
CONCLUSION:MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.
Microwave imaging is a safe and promising new technology in breast radiology, avoiding discomfort of breast compression and usage of ionizing radiation. This paper presents the first prospective ...microwave breast imaging study during which both symptomatic and asymptomatic subjects were recruited. Specifically, a prospective multicentre international clinical trial was performed in 2020-2021, to investigate the capability of a microwave imaging device (MammoWave) in allowing distinction between breasts with no radiological finding (NF) and breasts with radiological findings (WF), i.e., with benign or malignant lesions. Each breast scan was performed with the volunteers lying on a dedicated examination table in a comfortable prone position. MammoWave output was compared to reference standard (i.e., radiologic study obtained within the last month and integrated with histological one if available and deemed necessary by responsible investigator) to classify breasts into NF/WF categories. MammoWave output consists of a selection of microwave images' features (determined prior to trials' start), which allow distinction between NF and WF breasts (using statistical significance p<0.05). 353 women were enrolled in the study (mean age 51 years ± 12 SD, minimum age 19, maximum age 78); MammoWave data from the first 15 women of each site, all with NF breasts, were used for calibration. Following central assessor evaluation, 111 NF (48 dense) and 272 WF (136 dense) breasts were used for comparison with MammoWave output. 272 WF comprised 182 benign findings and 90 malignant histology-confirmed cancer. A sensitivity of 82.3% was achieved (95%CI: 0.78-0.87); sensitivity is maintained when limiting the investigation to histology-confirmed breasts cancer only (90 histology-confirmed breasts cancer have been included in this analysis, having sizes ranging from 3 mm to 60 mm). Specificity value of approximately 50% was achieved as expected, since thresholds were calculated (for each feature) using median value obtained after recruiting the first 15 women (of each site), all NF. This prospective trial may represent another step for introducing microwave imaging into clinical practice, for helping in breast lesion identification in asymptomatic women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylammonium lead tribromide (MAPbBr
) perovskite single crystals demonstrate to be excellent direct X-ray and gamma-ray detectors with outstanding sensitivity and low limit of detection. Despite ...this, thorough studies on the photophysical effects of exposure to high doses of ionizing radiation on this material are still lacking. In this work, we present our findings regarding the effects of controlled X-ray irradiation on the optoelectronic properties of MAPbBr
single crystals. Irradiation is carried out in air with an imaging X-ray tube, simulating real-life application in a medical facility. By means of surface photovoltage spectroscopy, we find that X-ray exposure quenches free excitons in the material and introduces new bound excitonic species. Despite this drastic effect, the crystals recover after 1 week of storage in dark and low humidity conditions. By means of X-ray photoelectron spectroscopy, we find that the origin of the new bound excitonic species is the formation of bromine vacancies, leading to local changes in the dielectric response of the material. The recovery effect is attributed to vacancy filling by atmospheric oxygen and water.
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IJS, KILJ, NUK, PNG, UL, UM
Methylammonium lead tribromide (MAPbBr3) perovskite single crystals demonstrate to be excellent direct X-ray and gamma-ray detectors with outstanding sensitivity and low limit of detection. Despite ...this, thorough studies on the photophysical effects of exposure to high doses of ionizing radiation on this material are still lacking. In this work, we present our findings regarding the effects of controlled X-ray irradiation on the optoelectronic properties of MAPbBr3 single crystals. Irradiation is carried out in air with an imaging X-ray tube, simulating real-life application in a medical facility. By means of surface photovoltage spectroscopy, we find that X-ray exposure quenches free excitons in the material and introduces new bound excitonic species. Despite this drastic effect, the crystals recover after 1 week of storage in dark and low humidity conditions. By means of X-ray photoelectron spectroscopy, we find that the origin of the new bound excitonic species is the formation of bromine vacancies, leading to local changes in the dielectric response of the material. The recovery effect is attributed to vacancy filling by atmospheric oxygen and water.
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IJS, KILJ, NUK, PNG, UL, UM
Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is ...corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients.
In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations.
About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations.
Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations.
Bacterial sepsis induces the production of excessive pro-inflammatory cytokines and oxidative stress, resulting in tissue injury and hyperinflammation. Patients recovering from sepsis have increased ...rates of central nervous system (CNS) morbidities, which are linked to long-term cognitive impairment, such as neurodegenerative pathologies. This paper focuses on the tissue injury and hyperinflammation observed in the acute phase of sepsis and on the development of long-term neuroinflammation associated with septicemia. Here we evaluate the effects of Coriolus versicolor administration as a novel approach to treat polymicrobial sepsis. Rats underwent cecal ligation and perforation (CLP), and Coriolus versicolor (200 mg/kg in saline) was administered daily by gavage. Survival was monitored, and tissues from vital organs that easily succumb to infection were harvested after 72 h to evaluate the histological changes. Twenty-eight days after CLP, behavioral analyses were performed, and serum and brain (hippocampus) samples were harvested at four weeks from surgery. Coriolus versicolor increased survival and reduced acute tissue injury. Indeed, it reduced the release of pro-inflammatory cytokines in the bloodstream, leading to a reduced chronic inflammation. In the hippocampus, Coriolus versicolor administration restored tight junction expressions, reduce cytokines accumulation and glia activation. It also reduced toll-like receptor 4 (TLR4) and neuronal nitric oxide synthase (nNOS) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome components expression. Coriolus versicolor showed antioxidant activities, restoring glutathione (GSH) levels and catalase and superoxide dismutase (SOD) activities and reducing lipid peroxidation, nitrite and reactive oxygen species (ROS) levels. Importantly, Coriolus versicolor reduced amyloid precursor protein (APP), phosphorylated-Tau (p-Tau), pathologically phosphorylated tau (PHF1), phosphorylated tau (Ser202 and Thr205) (AT8), interferon-induced transmembrane protein 3 (IFITM3) expression, and β-amyloid accumulation induced by CLP. Indeed, Coriolus versicolor restored synaptic dysfunction and behavioral alterations. This research shows the effects of Coriolus versicolor administration on the long-term development of neuroinflammation and brain dysfunction induced by sepsis. Overall, our results demonstrated that Coriolus versicolor administration was able to counteract the degenerative process triggered by sepsis.
Human scalp hair follicles (HFs) engage in olfactory receptor (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like ...odorant Sandalore® up-regulated HF antimicrobial peptide expression of dermcidin (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands.
To understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner.
DCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this treatment affected the HF microbiome.
Synthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs ex vivo. Combined antibiotic and odorant treatment, during an ex vivo dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured Staphylococcus epidermidis and Malassezia restricta over S. aureus and M. globosa, while exhibiting antimicrobial activity against Cutibacterium acnes. These effects were reversed by co-administration of Phenirat®.
We provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, ...therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52#177;1 yrs, BMI 27#177;7 kg/m.sup.2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score less than or equal to7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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