Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.

The introduction of tenofovir-derived prodrugs has revolutionised the prevention and management of HIV, which has coincided with 23% reduction in new HIV incidences globally. To date, there are two formulations of tenofovir-derived nucleoside reverse transcriptase inhibitor (NRTI): tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and tenofovir alafenamide fumarate/emtricitabine (TAF/FTC). Although these prodrugs have shown favourable safety profile, their effects on cardiovascular health are differ from one another: TDF/FTC exhibits potential lipid-lowering effect, TAF/FTC demonstrates potential lipid-inducing effect, which is a major risk factor for cardiovascular diseases. However, this issue has not been previously elucidated, especially among the marginalised populations [lesbian, gay, bisexual and transgender (LGBT) and men who have sex with men (MSM)] who are likely be the main users of these prodrugs. This is of clinically significance as the cardiovascular health in these populations is often overlooked, in addition to a lack of appropriate cardiovascular risk prediction algorithm. Therefore, this review aims to (1) highlight the cardiovascular risks of tenofovir-derived prodrugs in the marginalized populations, and also to (2) establish the importance of having a cardiovascular risk prediction model that is specific to this particular populations so that their health management could be more comprehensive.

SLM Additive Manufacturing has demonstrated great potential for aerospace applications when structural elements of individual design and/or complex shape need to be promptly supplied. 3D-printable AlSi10Mg (RS-300) alloy is widely used for the fabrication of different structures in aerospace industry. The importance of the evaluation of residual stresses that arise as a result of complex 3D-printing process thermal history is widely discussed in literature, but systematic assessment remains lacking for their magnitude, spatial distribution, and comparative analysis of different evaluation techniques. In this study we report the results of a systematic study of residual stresses in a 3D-printed double tower shaped samples using several approaches: the contour method, blind hole drilling laser speckle interferometry, X-ray diffraction, and Xe pFIB-DIC micro-ring-core milling analysis. We show that a high level of tensile and compressive residual stresses is inherited from SLM 3D-printing and retained for longer than 6 months. The stresses vary over a significant proportion of the material yield stress. All residual stress evaluation techniques considered returned comparable values of residual stresses even regardless of dramatically different dimensional scales from millimeters for the Contour Method down, laser speckle interferometry and XRD and down to small fractions of a mm (70 μm) for Xe pFIB-DIC ring-core drilling. The use of residual stress evaluation is discussed in the context of optimizing the printing strategy to enhance the mechanical performance and long-term durability.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Currently, data regarding optimal treatment modality, response, and outcome specifically for N3 head and neck cancer are lacking. This study aimed to compare the treatment outcomes between definitive concurrent chemoradiotherapy (CCRT) to the neck and upfront neck dissection followed by adjuvant CCRT. 93 N3 squamous cell carcinoma head and neck cancer patients were included. Primary tumor treatment was divided to definitive CCRT (CCRT group) or curative surgery followed by adjuvant CCRT (surgery group). Neck treatment was also classified into two treatment modalities: definitive CCRT to the neck (CCRT group) or curative neck dissection followed by adjuvant CCRT (neck dissection group). Overall, the 2-year overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 51.8%, 47.3%, 45.6%, and 43.6%, respectively. In both oropharyngeal cancer and nonoropharyngeal cancer patients, in terms of OS, LRFS, RRFS or DMFS no difference was noted regarding primary tumor treatment (CCRT vs. surgery) or neck treatment (CCRT vs. neck dissection). In summary, N3 neck patients treated with definitive CCRT can achieve similar outcomes to those treated with upfront neck dissection followed by adjuvant CCRT. Cautions should be made to avoid overtreatment for this group of patients.

The aim of this study was to assess if the ovine articular cartilage serine proteinase inhibitors (SPIs) were related to the Kunitz inter-α-trypsin inhibitor (ITI) family. Ovine articular cartilage was finely diced and extracted in 6M urea and SPIs isolated by sequential anion exchange, HA affinity and Sephadex G100 gel permeation chromatography. Selected samples were also subjected to chymotrypsin and concanavalin-A affinity chromatography. Eluant fractions from these isolation steps were monitored for protein and trypsin inhibitory activity and pooled fractions assessed by affinity blotting using biotinylated trypsin to detect active SPIs and by Western blotting using antibodies to α1-microglobulin, bikunin, TSG-6 and 2-B-6 (+) CS stub epitope generated by chondroitinase-ABC digestion. This identified 2-B-6 (+) positive 220-250,120, 58 and 36 kDa SPIs. The 58 kDa SPI contained α1-microglobulin, bikunin and chondroitin-4-sulphate stub epitope consistent with its identity as the α1-microglobulin-bikunin (AMBP) precursor and was also isolated by concanavalin-A lectin affinity chromatography indicating it had N-glycosylation. Kunitz protease inhibitor (KPI) species of 36, 26, 12 and 6 kDa could be autolytically generated by prolonged storage of the aforementioned 120 and 58 kDa SPIs; chymotrypsin affinity chromatography also generated the 6kDa SPI. KPI domain 1 and 2 SPIs were separated by concanavalin lectin affinity chromatography, domain 1 displayed affinity for this lectin indicating it had N-glycosylation. KPI 1 and 2 both displayed potent inhibitory activity towards trypsin, chymotrypsin, kallikrein, leucocyte elastase and cathepsin G. Localisation of versican, lubricin and HA in the surface regions of articular cartilage represented probable binding sites for the ITI SPs with likely importance in the preservation of joint function.

Zircon xenocrysts from alkali basalts in Ratanakiri Province, Cambodia, represent a unique low-Hf zircon, within a 12,000 km long Indo-Pacific megacryst zone. Colourless, yellow, brown and red crystals ({100}, {101}, subordinate {211}, {1103}), with hopper growth and corrosion features, range up to 20 cm in size. Zircon chemistry implicates juvenile, Zr-saturated, mantle-derived alkaline melt (Hf 0.6–0.7 wt%, Y <0.2 wt%, U+Th+REE <600 ppm, Zr/Hf 66–92, Eu/Eu*_N ~ 1, positive Ce/Ce*_N, HREE enrichment). Incompatible element depletion with increasing Yb/Sm_N from core to rim at ~ constant Hf suggests single stage growth. Ti-in-zircon temperatures (~570–740 °C) are lower than predicted by crystal morphology (800–900 °C) and decrease from core to rim (D_T = 10–50 °C). The d¹⁸O values (4.88 to 5.01‰ VSMOW) are relatively low for xenocrysts from the zircon Indo-Pacific zone (ZIP). The ¹⁷⁶Hf/¹⁷⁷Hf values (+ εHf 4.5–10.2) give T_{Depleted Mantle} model source ages of 260–462 Ma and T_Crustal ages of 391–754 Ma. The source magmas reflect variably depleted lithospheric mantle with little supracrustal input. Zircon U-Pb (0.88–1.56 Ma) and (U-Th)/He (0.86–1.02 Ma) ages are older than host basalt ages (~0.7 Ma), suggesting limited residence before transport. Zircon genesis suggests Zr-saturated, Al-undersaturated, carbonatitic-influenced, low-degree partial melting (<1%) of peridotitic mantle at ~60 km beneath the Indochina terrane.

The application of a commonly used computer algorithm based on the group-additivity method for the calculation of the liquid viscosity coefficient at 292.15K and the activity coefficient at infinite dilution in water at 298.15K of organic molecules is presented. The method is based on the complete breakdown of the molecules into their constituting atoms, further subdividing them by their immediate neighbourhood. A fast Gauss-Seidel fitting method using experimental data from literature is applied for the calculation of the atom groups’ contributions. Plausibility tests have been carried out on each of the calculations using a 10-fold cross-validation procedure which confirms the excellent predictive quality of the method. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the viscosity coefficient, expressed as log(η), was 0.9728 and 0.11, respectively, for 413 test molecules, and for the activity coefficient log(γ)^∞ the corresponding values were 0.9736 and 0.31, respectively, for 621 test compounds. The present approach has proven its versatility in that it enabled at once the evaluation of the liquid viscosity of normal organic compounds as well as of ionic liquids.

The paper investigates the accuracy of the angular velocity estimation based on measurements of the components of the induction vector of the Earth's magnetic field. A comparative analysis of angular velocity estimates using the Boer formula, the derivative of the induction vector of the Earth's magnetic field and direct measurements of the components of the angular velocity vector using a gyroscopic sensor for the ISOI small spacecraft (SXC3-219) is carried out. The results obtained make it possible to investigate the accuracy of estimates of the angular velocity of a small spacecraft in various ways to improve the quality of its target tasks.

The purpose of the research was to obtain information about the necessity and efficiency of the application of localized irrigation to some qualitative indices of plum trees in the nursery, against the background of different fertilization treatments. The expected results to be obtained by applying differentiated rules of irrigation and fertilization will consist in obtaining a healthy, vigorous fruit tree planting material, increasing production in the nursery. With fruit trees in the nursery, as with all cultivated plants, the growth process depends to the greatest extent on the climate and soil conditions available to them. The use of fertilizers in tree culture becomes necessary to renew the reserve of nutrients consumed by plants or leached in depth, then to improve the physical condition, the chemical composition, and the overall state of fertilization of the soil. It is necessary to intervene every year, in several rounds, with fertilizations that ensure, on the one hand, the achievement of a certain level of production, and on the other hand, a certain level and ratio of nutritional elements by returning the amounts of elements easily accessible nutrients extracted with the harvest to be able to maintain, in this way, the fertility of the soil in accordance with the age of the plantation and the level of production. The two varieties of plum studied were Stanley and Cacanska Lepotica, two valuable varieties for the quality of the fruit. During the research, the fertilization treatments had the highest contribution (34.50 %) on the stem diameter, compared to irrigation (20.67 %) and respectively the variety (5.63 %), considering that the variety did not significantly influence the increase in diameter of the grafted trees.

Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is recognized for being associated with severe cases of the disease. This study conducted the phylogenetic investigation of DENV-2 in the Northern region of Brazil. DENV-2 isolates from 2017 to 2021, originating from Northern Brazilian states, were selected. Only one lineage (I) of the Asian-American genotype and one lineage (5) of the cosmopolitan genotype were observed. All sequences of the Asian-American genotype used in this study were segregated into a paraphyletic subgroup aligned with sequences from an American clade. These results indicate a probable geographic link starting from Puerto Rico. Additionally, sequences from Acre were identified and grouped into a monophyletic clade of the cosmopolitan genotype. These results indicate the cocirculation of two DENV-2 distinct lineages: Lineage 1, Asian-American genotype (probable origin from Puerto Rico); Lineage 5, cosmopolitan genotype (probable origin from Peru). Our results provide important data regarding the study of DENV genotypes and lineages distribution, as well as opening up possibilities for probable introduction and dissemination routes.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress has a severe effect on low-density lipoprotein (LDL) oxidation, leading to several detrimental health effects. Thereof, in this study, the effect of beeswax alcohol (BWA) was evaluated to prevent LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipoprotein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle and older human subjects (n=50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better them the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails CuSO4 (final 0.5 μM) evoked LDL/apo-B oxidation and a marked reduction of lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counter carboxymethyllysine (CML, 500 ng) induced toxicity and rescued zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blind, placebo-controlled preliminary clinical study on middle and older-aged human subjects (n=50) exhibited that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA), total hydroperoxides, and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in anthropometric profile, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and has a positive impact on the oxidative variables of human subjects.

In PVC compounds, hydrogen chloride plays a fundamental role in .H and .OH radical trapping lowering the flame energy during combustion. Furthermore, it yields actual Lewis acids promoting the cross-linking of the polyene sequences from PVC degradation and bringing a char layer, protecting PVC items from flames. Therefore, PVC is inherently flame retarded. However, plasticized PVC requires flame retardants and smoke suppressants to enhance fire performance. Low smoke acidity PVC compounds contain potent acid scavengers capable of acting at high temperatures. They react with hydrogen chloride in the condensed phase, making it unavailable in the gas and even in the condensed phase, compromising the reaction to fire and enhancing the smoke produced during the combustion. The effect of the sequestration of hydrogen chloride in PVC compounds for cables by potent acid scavengers has been studied in this paper through measurements of oxygen index, heat release, and smoke production. It is shown that potent acid scavengers strongly affect parameters like fire growth rate in cone calorimetry, specific (total) heat capacity, and specific heat of combustion of fuel gases in micro combustion calorimetry. They neutralize the action of antimony trioxide and Lewis acid precursors commonly used as flame retardants and smoke suppressants in PVC items, making them prone to ignite, release smoke, and spread flame. A new generation of flame retardants and smoke suppressants is necessary to keep low smoke acidity and high fire performances together in PVC items

As a form of protection, a nature park is often created to protect and valorise natural and cultural heritage in peripheral rural areas. However, in terms of multi-functionality, new nature parks are incorporated into traditional productive activities, such as recreational and tourist activities, which sometimes compromise sustainability. The research objective is to study the relationship between tourism and sustainability in the Nature Parks of “Sierra de Aracena y Picos de Aroche”, “Sierra Norte de Sevilla” and “Sierra de Hornachuelos” that makes up the Dehesas de Sierra Morena Biosphere Reserve in Andalusia, Spain. Therefore, selective interviews have been carried out with the stakeholders to establish their perception of sustainable tourism and the presence of dominant discourses. The main conclusions indicate (1) the presence of different dominant discourses on sustainability, namely the conservationist and mercantilist ones, with the prevalence of the economic dimension; (2) poor awareness and adaptation to the context of global change; and (3) the presence of competitive relationships that generate difficulties for the governance of sustainable tourism.

Nitrogen and phosphorous loading drives eutrophication of aquatic systems. Lakes and reservoirs are often effective N and P sinks, but information is needed on the variability of their biogeochemical dynamics, especially for tropical systems. A long-term N and P mass balance (2003-2018) in a small tropical eutrophic reservoir lake, Valle de Bravo (VB), Mexico, showed it is a net sink of N (-41.7 g N m-2 y-1), and P (-2.7 g P m-2 y-1), mainly through net sedimentation, equivalent to 181% and 68% of their respective loading (23.0 g N m-2 y-1 and 4.2 g P m-2 y-1). N mass balance showed that VB has a high net N atmospheric influx (31.6 g N m-2 y-1), which was 1.3 times the external load, and likely dominated by N2 fixation. During a period of high water level fluctuations (WLF), the net N atmospheric flux decreased by half compared to high level years. WLF can be a useful management tool to improve the trophic status of water bodies by decreasing anoxic conditions and net atmospheric fluxes, possibly through decreasing nitrogen fixation and/or promoting denitrification and other microbial processes that alleviate the N load.

Brucellosis infection induces fever, chills, sweats, headache, myalgia, arthralgia, anorexia, fa-tigue, and mood disorders. In mice, it causes a rise in IL-6, TNF-, and IFN-; and reduces sero-tonin and dopamine levels in hippocampus. There is loss in muscle strength and equilibrium and increased anxiety and hopelessness. Imipramine (ImiP) is a tricyclic antidepressant that increases the capacity of macrophages to destroy intracellular microorganisms in vivo. The effect of ImiP was evaluated in Balb/c mice infected with Brucella abortus 2308. Serum levels were determined in IFN-, IL-6, TNF-, IL-12, MCP-1, and IL-10 by FACS; the bacterial count in the spleen, by CFU; the serotonin concentration in the hippocampus, by HPLC; and strength, equilibrium, and mood by behavioral tests. Our results showed that infected vs. control mice had a significant rise in lev-els of IFN-, IL-6, TNF-, and IL-12 with a low IFN-/IL-6 ratio, elevated bacterial-counts, alter-ations in serotonin concentration at hippocampus, and decreased muscular strength, equilibrium, and mood. Infected mice treated with ImiP vs. infected mice showed: 1) improved mood; 2) in-creased hippocampal serotonin availability, splenic dendritic cells, and macrophage phagocytic activity; and 3) upturn inflammation and reduced CFU ability. Our results support that ImiP fa-vors positive outcomes in subjects handling Brucella infections likely by improving psychoim-mune resilience.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

The hypothesis that consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased procollagen I concentration in the bone tissue and weakened biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for the skeleton protection under low-level and moderate chronic exposure to Cd.

The bulk planetary compositions are thought to be linked to the chemical abundances of their host stars. The abundances of 8 key rock-forming elements and the key planetary abundance ratios in G– and F–type main sequence stars located in the Solar neighborhood within 50 pc were statistically analyzed. The averaged C/O, Mg/Si, and Fe/Si elemental ratios of the planetary systems have a crucial role in the chemical composition and the mineralogy of a rocky planet's interior. We also studied the variation of the calculated Ca/Si, Al/Si, Na/Si and Fe/Si ratios in the samples of the examined stars using the Ca, Al, Na, and Fe abundances from the catalog and then attempt to constitute plausible occurrence trends of the analyzed abundance ratios for the rocky planet population in the near – solar galactocentric distances. Considering these results, we provide simple predictions for the most likely bulk compositions of the potential rocky planets. We further apply our results to compare them to the solar averaged abundance ratios, finding that the key elemental ratios for rocky planet composition in the Solar System are not typical amongst most of the studied stellar samples.

Communicating about sex is important in generating positive perceptions about one’s sexual and romantic life. The last decade has provided insight into the theoretical applications on sex communication research. While the focus on extant research focuses on the psychological processes’ individuals employ to talk about sex, no theoretical framework exists that identifies key constructs that provides a parsimonious understanding about the communicative processes of sex and sexuality. This review sought to identified key constructs that are suitable to develop a sex talk theory. In the current project, we reviewed 24 studies including 8,698 participants (Mage = 24.98) that applied a theoretical framework to sex research. This review identified three salient constructs (e.g., disclosure, cognitive, and relational and behavioral) that are important for a sex talk theory. Last, this review indicated that scholarship should explain the relationships between the key constructs. We provided several recommendations that scholars should take when developing a theory in sex communication research.

Abstract Introduction: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomized controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. Method: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medical event following immunisation (MEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded “Yes” to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an MEFI/AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. Results: A total of 704 (31%) participants responded to the SMS prompts, with 75% (528/704) indicating “No” and 25% (176/704) "Yes” to experiencing a MEFI. However, 31% (55/176) who responded “Yes” did not complete a CATI survey, but 69% (121/176) did; and 64% (77/121) of these indicated negative to AEFI experience whilst 36% (44/121) were affirmative. There were no AEFI reported in control group participants. Zm-STARSS showed promising results in that the AEFI detection rate using SMS-CATI was 2% (44/2280) on an intention to treat cohort. Conclusion: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in LMICs for all vaccines.

Background: Cardiovascular disease (CVD) has been one of the leading causes of death and disability-adjusted life years lost worldwide. Blood pressure, lipid, and cholesterol are good predictors of CVD risk and correspond upon age and physical fitness. However, few studies have explored the variation trend of CVD risk factors across different populations upon age and their muscle strength. Objective: to analysis the variation tendency of CVD risk factors in blood according to age and relative grip strength among different populations. Method: 25363 participants were recruited in this cross-sectional study and 24709 were included in the analysis. A logistic regression and a Bayesian probabilistic analysis based on Markov Chain Monte Carlo (MCMC) Modeling is conducted to build probability prediction models of hypertension, hyperlipidemia, and hypercholesterolemia according to age, relative grip strength, body weight conditions, and physical activity levels. Results: 1) age might be the main influence factor of hypertension, which is regarded as one of the primary CVD risk factors. However, although keeping a high level of physical activity might have positive effect on preventing hypertension because that individuals with normal body weight and higher physical activity shows a lower probability of being diagnosed with hypertension, it might could not prevent individuals from getting hypertension with age. 2) After 60, individuals of normal body weight seem more likely to have hyperlipidemia than those are overweight or obese. 3) Larger relative grip strength might not be able to offset the negative effects of obesity, overweight and physical inactivity on hyperlipidemia. 4) The probability of getting hypercholesterolemia varies less with age and relative grip strength. Conclusion: Body weight management and keeping high levels of physical activity are recommended at any age. It might benefit to increase some bodyweight after 60 years old.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

Estimation of the reality can easily be flawed, hence, in order to result in accurate and useful estimates the process has to be protected from bias and confounding and should follow other methodological milestones inherent to different types of empirical observations. Candidate-gene association studies are a specific form of observations that have been rather extensively applied in psychiatry yielding valuable information on various aspects – when methodologically adequate and used in appropriate settings. However, certain flaws that may occur in such studies might not be bluntly obvious, at least not at first glance, and may pass unnoticed by researchers and reviewers. This case study uses two recent published candidate-gene association reports suggesting involvement of cannabinoid receptor type 1 and of heat shock protein single nucleotide polymorphisms in development of neurocognitive performance and psychopathology in a cohort of adult first episode psychosis patients to point-out the types of flaws inevitably resulting in inaccurate and useless estimates.

Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tear (sPTRCT) with fresh, uncultured, unmodified, autologous adipose derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to physical therapy treatments for at least six weeks were randomly assigned to receive a single injection of an average 11.4×10⁶ UA-ADRCs (in 5 mL liquid; mean cell viability: 88%) (n=11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/ml; 2 mL) plus 3 mL of 0.25% bupivacaine (n=5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey and pain visual analogue scale (VAS) at baseline (BL) as well as three weeks (W3), W6, W9, W12, W24, W32, W40 and W52 post treatment. Fat-saturated T2 weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment. Results: No severe adverse events related to the injection of UA-ADRCs were observed in the 12 months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. However, one subject in the corticosteroid group developed a full rotator cuff tear during the course of this pilot study. Despite the small number of subjects in this pilot study, those in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than those in the corticosteroid group (p < 0.05). Discussion: This pilot study suggests that the use of UA-ADRCs in subjects with sPTRCT is safe and leads to improved shoulder function without adverse effects. To verify the results of this initial safety and feasibility pilot study in a larger patient population, a randomized controlled trial on 246 patients suffering from sPTRCT is currently ongoing.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

Abstract Introduction: Visual perceptual skills are essential for independent participation in self-care tasks, educational, work and leisure time activities. The effect of HIV on the visual perceptual skills is not well understood among children in low resource settings like Zimbabwe. Methods: A cross sectional comparative study was done with 30 children living with HIV and 30 children living without HIV residing in Harare urban area. The TVPS-3 was used to assess their visual perceptual skills. SPSS version 22, STATISTICA 13 and Microsoft 2016 were used for data analysis. Results: Both groups of children had mean percentile ranks below 50 on their TVPS-3 scores. Children without HIV generally performed better than those with HIV but the difference was not statistically significant in most cases. Through univariate analysis, only performance on Spatial Relations significantly differed between the two groups. Both groups had lowest scores in Basic visual perceptual skills. Age and school grade were the independent predictors of the children’s performances in the study. Conclusion: There is need for Occupational therapy services in public primary schools and in the pediatric Opportunistic Infections clinics in hospitals to be part of the health team which caters for children with visual perceptual challenges.

Background: Research articles are essential for describing new ideas, techniques, and procedures and consolidating concepts. It creates an opportunity to expose studies and publicly assimilate published knowledge. Therefore, one of them is the most used and accepted index to verify the author’s scientific impact is the H-index or Hirsch index. It provides a robust single metric that combines quality and quantity. Therefore, it presents disadvantages, (1) researchers with shorter scientific carriers may have fewer articles and citations than those with longer scientific life; (2) it allows scientists to receive citations even if no new papers are published; (3) it is only useful for comparing the better scientists in a field; (4) this indicator can never decrease; (5) it is only weakly sensitive to the number of citations received; (6) the major and minor (or no) contributor in the research gained equal h-index. Then, the H-index ignores the total of citations and the time of a researcher's experience (“scientific age” [sa]). Objective: Thus, the goal of this study was to present a new index system (GFsa index ©) based on the two variables completely forgotten (total of citations and “scientific age”), introducing a new terminology “scientific age”, to evaluate the best-ranked researchers in Dentistry. Methods: The AD Scientific Index was used, and all researchers included in this study were cited in the AD Scientific Index (2024) in the Dentistry field and had the Google Scholar page accessible for a consultation to manually obtain the total of citations and calculate the “scientific age”. The information was retrieved by two authors (G.V.O.F. and J.C.H.F.), who assessed the data twice to avoid errors or mistakes. For inclusion: a minimum H-index value of 30; for exclusion: (i) the author did not have a Google Scholar page; (ii) duplicated author; or (iii) presented any suspicious activities about manipulation of articles. Then, a dataset of all researchers who were reported in Dentistry was prepared (name, H-index, i10 index, and publications). The formula developed and applied was GFsa=(total number of citations)/(“scientific age)². The Pearson correlation statistically evaluated the data obtained; the confidence interval was 95%. Results: A total of 9,093 researchers in Dentistry were recorded, of whom 1,020 were included. Then, we collected all 1,020 researchers' Google Scholar data (publications, citations, and indexes), and each researcher's total citations and “scientific age” were registered and calculated. The mean “scientific age” registered was 34.18 ± 13.34 (standard error of mean = 0.4181). With this information and data collected, GFsa index © was calculated, presenting a minimum value of 0.2186 and a maximum of 154.8 (mean = 10.33 ± 11.82; standard error of mean = 0.3706). Then, the data was organized and sorted following the ranking obtained in the GFsa index ©. The Pearson correlation showed that the H-index had a weakly positive association with the researcher’s “scientific age”; this fact means that the H-index will increase according to the “scientific age” increase. Otherwise, a moderately negative correlation between GFsa and “scientific age” was demonstrated, whereby a higher GFsa © had a lower “Scientific age”. This assessment shows that the variables introduced were fairly used. Moreover, a positive correlation was observed between both indexes (H-index and GFsa). Conclusion: It is possible to conclude that the new variable reported (“Scientific age”) and using the total citations brought a fairer and more feasible evaluation among the researchers. Thus, we are launching the new GFsa index © and the new information named “Scientific age” for the first time in the literature. The future perspective of the GFsa © application will be (1) the evaluation of the 9,093 researchers in Dentistry (total initially registered), including more authors/researchers in the Dentistry field, (2) expanding the exposition of this new index for other areas of the knowledge, and (3) provide free access of all data through the website (http://gfindex.us.to).

Coronavirus disease 2019 (COVID-19), can manifest with ocular symptoms. These symptoms can be divided into isolated events attributed to COVID-19 and those occurring in multisystem inflammatory syndrome in children (MIS-C), a newly diagnosed disease entity associated with COVID-19 infection. Currently, the literature lacks specific guidelines and treatment regimens for COVID-19 ocular symptoms, especially in children.

Like all RNA viruses, SARS-CoV-2 shows high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season due to climate change in Italy, the first Western country to have been hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58,85 million people. Methods: during the state of national health emergency and the Draghi government, the Civil Defense Department daily released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions, and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing COVID-19 pandemic in Italy during the summers 2020 (following the nationwide lockdown), 2021 and 2022. Results: from summer 2020 (before mass vaccination) to summers 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination) all pandemic trend indicators have showed a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6.850% (i.e. ≈68,50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. Conclusions: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climate may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is obviously not absolute but limited, also taking into account that vaccine protection wanes considerably after 6 months. It follows that a subject vaccinated at the beginning of winter will not be completely covered in the height of summer, without forgetting the unvaccinated. As a final remark, the long nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during summer 2020.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aβ cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer’s disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid β-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features and % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aβ-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

On 14 March 2020 the state of epidemic threat was introduced in Poland applicable until 20 March 2020 when the state of epidemic was introduced in the territory of the Republic of Poland. The situation associated with the growing number of SARS-CoV-2 infections forced ongoing monitoring of the epidemic situation, which entailed an introduction of a number of restrictions and solutions intended to isolate the infected persons on the one hand, and to minimize the risk of development of an epidemic in Poland on the other. Activity of the Polish legislator is also essential, which tried to introduce solutions that would correspond with current expectations and needs. In this paper, the author points to the issues of communication with a public authority by specific reflections on the principles of serving documents on beneficiaries of EU programs under which they were awarded funding for their implementation. The author points to the dynamics of the legislator’s work in this respect by analyzing the rules for serving documents by a public authority on beneficiaries who are public entities and those who are not.

Analyses of the Hubble diagrams are presented for SN1a supernovae and gamma ray bursts in the redshift ranges z = 0.01–1.3 and 0.034–8.1, respectively. Data are presented on the typical z/μ scale and also on the less common yet increasingly sensitive photon flight time t/(z+1) scale. The primary conclusion is that on the basis of the presently accessible data in the redshift range z = 0.01–8.1, the slope of the Hubble diagram is, or is extremely close to, exponential.

This article is a tribute to Lewis Wolpert on the occasion of the recent 50th anniversary of the publication of his article ‘Positional Information and the Spatial Pattern of Differentiation’. This tribute relates to another of his ideas: his early ‘Progress Zone’ timing model for limb development. Recent evidence is reviewed that a mechanism sharing features with this model patterns the main body axis in early vertebrate development. This tribute celebrates the golden era of Developmental Biology.

The European Space Agency (ESA) defines as Earth observation (EO) Level 2 information product a single-date multi-spectral (MS) image corrected for atmospheric, adjacency and topographic effects, stacked with its data-derived scene classification map (SCM), whose thematic map legend includes quality layers cloud and cloud-shadow. ESA EO Level 2 product generation is an inherently ill-posed computer vision (CV) problem never accomplished to date in operating mode by any EO data provider at the ground segment. Herein, it is considered: (I) necessary not sufficient pre-condition for the yet-unaccomplished dependent problems of semantic content-based image retrieval (SCBIR) and semantics-enabled information/knowledge discovery (SEIKD) in multi-source EO big data cubes. (II) Synonym of EO Analysis Ready Data (ARD) format. (III) Equivalent to a horizontal policy for background developments in Space Economy 4.0. In compliance with the GEO-CEOS Quality Assurance Framework for EO Calibration/Validation guidelines, to contribute toward filling an analytic and pragmatic information gap from multi-sensor EO big data to timely, comprehensive and operational EO value-adding information products and services, this work presents an innovative AutoCloud+ CV software toolbox for cloud and cloud-shadow quality layer detection in ESA EO Level 2 product. In vision, spatial information dominates color information. Inspired by this true-fact, the inherently ill-posed AutoCloud+ CV software was conditioned, designed and implemented to be “universal”, meaning fully automated (no human-machine interaction is required), near real-time, robust to changes in input data and scalable to changes in MS imaging sensor’s spatial and spectral resolution specifications.

The pathophysiologic substrate of pediatric hydrocephalus has not been thoroughly explained. Because of that, the available treatment options and protocols will be largely based on expert opinions or the results of single-center databases, until a more comprehensive knowledge of the various subcategories of hydrocephalus is undertaken. In retrospect, we mention that valve-based shunt systems have been constituting the mainstay of therapy since the late 1950s. The initially used shunt systems were concerning the ventricular system and the atrium. In the 1970s, VA shunts were not the main stay of treatment, as the primary location for the distal end was substituted by the peritoneum, due to the emergence of the ventriculoperitoneal shunts. Several types of one-way valve-based shunt systems have been developed. The ultimate goal was the drainage of the appropriate amount of CSF, in order to avoid either overdrainage or underdrainage, without interfering with normal brain development or cognition. Our review briefly analyzes these valve types and attempts a comparison, based on their functional characteristics. In addition to the peritoneum, other distal locations for shunt placement have been explored, including the pleural space and gallbladder. A separate subcategory includes the shunt systems which incorporate the lumbar subarachnoid space as the proximal location for the central catheter. Nowadays, the only available surgical alternative for the treatment of hydrocephalus is ETV. Since 2000, approximately 50% of children suffering hydrocephalus have been considered to be candidates for the execution of ETV. The potential benefits are that it closely resembles to the normal, physiological pathway of CSF absorption, thus circumventing the need for an artificial shunt system. Moreover, this technique is associated with lower infection rates, as well as on average, with a lower reoperation rate. Attempts of future progression are largely based on the development of improved shunt valve systems that could be affordable worldwide, as well as with the constant availability of ETV in developing countries. Another term that deserves special mention is related with the outcome of ETV in children who had a medical history of previously incorporated shunts and who were subsequently experiencing shunt dysfunction. This subset of patients is discussed in terms of efficacy (success rate from 40% to 80%) and safety (0%–32.5% of complications). Based on literature reviews, well-recognized predictive factors associated with secondary ETV failure include age, early onset of hydrocephalus, and prematurity. Currently, there is no consensus when the optimum surgical strategy is concerned in the different subgroups of patients, who are suffering from shunt dysfunction. Therefore, another issue that this review attempts to elucidate is the identification of subgroups of patients in whom shunt treatment is associated with a favorable outcome, compared to ETV, and vice versa. The objective of our study is to evaluate the comparative safety and efficacy, as well as the outcomes, of shunting and ETV in pediatric hydrocephalus cases. Anatomic and molecular substrate of hydrocephalus need to be better elucidated, so that medications or genetic modifications become more effective in order to offer a potential cure for hydrocephalus. Advancements in the treatment of hydrocephalus will depend on research into the shared molecular mechanism underlying various forms of the condition, paving the way for new therapeutic strategies.

The lack of a Dengue vaccine and pharmacological antiviral drugs has made Vector Control Programs the primary resource in the fight against arboviral diseases. Although Integrated Management and Control programs implement intense control measures for adult, pupal, larval, and breeding sites during outbreaks, there is a lack of studies to understand the role of the vector egg stage in disease dynamics. This study aimed to assess the dry season quiescent Aedes aegypti and Aedes albopictus egg populations in houses and backyards in the tropical city of Tapachula, southern Mexico. Two hundred fifty ovitraps were placed in 125 homes in the Las Americas neighborhood. A total of 7,290 eggs were collected from 211 (84.4%) ovitraps, with 4,031 (71.1%) identified as Ae—aegypti, and 1,636 (28.8%) as albopictus, respectively. Eighty-three larval sites were sampled with desiccated eggs during the dry season; most of them were described as trash-like because larvicides are only used for larger containers of 5-10 L. Evolutionary characteristics for the two species include rapid and delayed hatching of eggs, ambient-regulated quiescence, the ability of the embryo to survive for a more extended period intra-seasonally, and the sticking of egg walls to container walls. This demands urgent operational research to achieve successful egg-proof larval container methods.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Aim To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. Materials and methods We conducted a retrospective monocentric observational study over a 3 years period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint or tyrosine kinase inhibitors (ICIs or TKIs) as of January-2017. Imaging reports were analysed by two physicians in consensus. Anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results Eighty patients were included and 195 couples of scans analysed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The more frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions Treatment monitoring with 18F-FDG

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Monitoring the quality of stored bulk grain is generally done using temperature cables hung from silo roofs. Little investigation has been done into the effects of number of sensors and their placement in terms of reliability of the monitoring system with regard to making stored grain quality management decisions. A previously developed 3D finite element simulation model was verified and used to investigate these aspects. In the first study, a silo was loaded with about 228.6 Mg (9000 bushels) of maize and six temperature cables were placed in the grain mass. The maize was aerated continuously for a period of two weeks, and the cable sensor temperatures were compared to the predicted temperatures which were in close agreement with the observed readings. The standard error of prediction ranged from 2.0 to 3.7°C. In the second study, 15 and 30 sensors were placed at manufacturer recommended depths and horizontal locations in the grain mass of three silo sizes (i.e., 11x11, 14.6x14.6 and 14.6x18.3 m diameter by eave height). The average grain temperatures predicted by the 15 and 30 sensors over a one-year simulation period were compared to the average grain temperatures predicted for the entire grain mass (1968, 3052, and 3204 mesh nodes). The number of sensors needed to monitor stored grain temperatures reliably in the three silo sizes investigated heavily depended on whether the aeration control strategy achieved a sufficiently low temperature by the time the aeration fans were turned off and sealed ahead of the non-aerated storage period. Fifteen or 30 sensors were sufficient to monitor grain temperatures during the aeration cooling period but for the two larger silo sizes more than 30 sensors would be needed during the storage period. As silo size increased, and surface-to-volume ratio decreased, grain temperatures remained lower during the storage period. Results support the best management practice recommendation of leaving cooled grain cold and not warming it up in the spring ahead of storage into the summer.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

The photophysical properties of Cu(II) complexes with 5,10,15,20-meso-tetrakis(phenyl)porphyrin and 5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin were examined by luminescence and femtosecond time-resolved absorbance methods respectively. These studies were supported by DFT and TD-DFT calculations which highlight the important role played by a ligand-to-metal charge-transfer states in directing the system towards either intersystem crossing to the triplet hypersurface or coordinative expansion to a five-coordinate quasi-stable intermediate. The latter processes occurs when the porphyrin is photolyzed in the presence of suitably located Lewis bases. Femtosecond time resolved absorbance measurements on Cu(II)-5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin confirm that the coordinative expansion in water occurs in approximately 700 fs while crossing to the triplet hypersurface takes approximately 140 fs in the same solvent. These processes are mutually exclusive, but both can occur simultaneously depending on the environment of the porphyrin. The ratio of the two processes depends on the relative orientation of the Lewis base with respect to the copper atom at the time of excitation. As a consequence, copper porphyrins such as these, are excellent probes to the environment of the porphyrin, and can be used to identify the location of the porphyrin when interacting with DNA fragments.

Let  β= (((24!)!)!)!, and let {${\mathcal P}_{n^2+1}$} denote the set of all primes of the form {$n^2+1$}. Let ${\mathcal M}$ denote the set of all positive multiples of elements of the set {${\mathcal P}_{n^2+1} \cap (\beta,\infty)$}. The set {${\mathcal X}=\{0,\ldots,\beta\} \cup {\mathcal M}$} satisfies the following conditions: (1) ${\rm card}({\mathcal X})$ is greater than a huge positive integer and it is conjectured that ${\mathcal X}$ is infinite, (2)} we do not know any algorithm deciding the finiteness of ${\mathcal X}$, (3)~a~known and short algorithm for every {$n \in N$} decides whether or not {$n \in {\mathcal X}$}, (4) a known and short algorithm returns an integer~$n$ such that ${\mathcal X}$ is infinite if and only if ${\mathcal X}$ contains an element greater than $n$. The following problem is open: {\em simply define a set {${\mathcal X} \subseteq N$} such that ${\mathcal X}$ satisfies conditions (1)-(4), and \underline{we do not know any representation of~~${\mathcal X}$~~as a finite union of sets whose definitions are simpler than} \underline{the definition of ${\mathcal X}$}} {\tt (5)}. Let {$f(1)=2$}, {$f(2)=4$}, and let {$f(n+1)=f(n)!$} for every integer {$n \geqslant 2$}. For a positive integer $n$, let {$\Psi_n$} denote the following statement: {\em if a system of equations ${\mathcal S} \subseteq \Bigl\{x_i!=x_k: i,k \in \{1,\ldots,n\}\Bigr\} \cup \Bigl\{x_i \cdot x_j=x_k: i,j,k \in \{1,\ldots,n\}\Bigr\}$ has only finitely many solutions in positive integers \mbox{$x_1,\ldots,x_n$}, then each such solution \mbox{$(x_1,\ldots,x_n)$} satisfies {$x_1,\ldots,x_n \leqslant f(n)$}.} We prove that for every statement $\Psi_n$ the bound {$f(n)$} cannot be decreased. The author's guess is that the statements {$\Psi_1,\ldots,\Psi_9$} are true. We prove that the statement $\Psi_9$ implies that the set ${\mathcal X}$ of all {non-negative} integers $k$ whose number of digits belongs to {${\mathcal P}_{n^2+1}$} satisfies conditions {\tt (1)-(5)}.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune mediated rheumatic disesases (IMRD) patients are scarce. This study describes breakthrough COVID-19 among IMRD patients participating of SAFER-study, a Brazilian multicentric cohort evaluating safety, effectiveness and immunogenicity of SARS-Cov-2 vaccines in autoimmune diseases. Descriptive analysis and a binary logistic regression model, to evaluate predictors of COVID-19-related hospitalization, were performed. P-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with mean (SD) age 40.23 (13.19) years. Patients received 2 (19%), 3 (70%) or 4 (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n=150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n=112) was with BNT162b2 (40%) or ChAdOx1 (26%). COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84, CI: 1.9-18.5, p=0.002) and treatment with corticosteroids (OR: 2.94, CI: 1.02-8.49, p=0.0043) associated with higher odds of hospitalization, while the increasing number of vaccine doses was protective (OR: 0.37, CI: 0.15-0.9, p=0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favour of booster vaccination in IMRD patients.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.