Humeral resurfacing arthroplasty (HRA) entails the substitution of the articular surface alone with a prosthetic cap without stem. It is a more conservative procedure which can be easily converted in a total arthroplasty if necessary. The present study aimed to evaluate the clinical and radiographical outcomes in a series of patients treated with HRA. 33 patients with a mean fol-low-up of 11 years were clinically (Constant score; Disability of the Arm, Shoulder and Hand score, DASH) and radiographically assessed before and after surgery. Constant and DASH score improved significantly after surgery, and only 2 cases needed revision surgery. HRA represents a valid therapeutic option in selected cases to improve the quality of life and delaying the need for more invasive procedures.

Aims of the paper are the results of a research on a wooden box that holds an important historical document, which is a hand Bible handwritten in the thirteenth century. The tradition connect this Bible to the name of Marco Polo (Venice, 1254 - Venice, 1324), who would be the owner and that it would accompany him on his travels (1262 and 1271) in China. The Bible, of fine workmanship, written on thin parchment, and its container, along with a yellow silk cloth, is preserved in the ancient and prestigious Laurentian Library in Florence. The manuscript was in very poor condition and in the course of the study (2011) was being restored. Aims of survey were to determine the place and period of realization of the box, or rather if it be contemporary or later than the manuscript it contains and whether it was made in the East or in Europe.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

The extensive use of rare earth elements (REEs) in a number of technologies is expected to impact on human health, including occupational REE exposures. A body of experimental evidence on REE-associated toxicity has been accumulated in recent decades. Unlike experimental studies, the consequences of REE exposures to human health have been subjected to relatively fewer investigations. Geographical studies have been conducted on residents in the Chinese REE mining districts, reporting on REE bioaccumulation, and associations between REE residential exposures and adverse health effects. A more limited series of studies has been focused on occupational REE exposures, such as movie operator (with occurrence of cerium aerosol) with the observation of pneumoconiosis and lung fibrosis. Similar effects have been reported in case reports for other workers, such as a lens grinder and a printer exposed to carbon-arc lamp emission. As for the occupations related to REE mining and processing, REE bioaccumulation in scalp hair and excess REE urine levels were reported. A study was devoted to workers employed in e-waste separation, showing alterations of several plasma markers. As for other REE occupational exposures, mention should be made of: a) mechanical workshops, with exposures to diesel exhaust microparticulate (containing nanoCeO₂ as a catalytic additive) and, b) production and manufacture of REE supermagnets for hybrid engines and wind turbines. Diesel exhaust microparticulate has been studied in animal models, leading to evidence of several pathological effects in animals exposed by respiratory or systemic routes. As for supermagnet production and manufacture, a body of literature is reviewed of experimental studies, and of human exposure studies showing several pathological effects of static magnetic fields, warranting further investigations.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Volatility is the most widespread measure of risk. Volatility modeling allows investors to capture potential losses and investment opportunities. This work aims to examine the impact of the two waves of COVID-19 infections on the return and volatility of the stock market indices of the euro area countries. The study also focuses on other important aspects such as time-varying risk premium and leverage effect. Thus, this investigation employed the Threshold GARCH(1,1)-in-Mean model with exogenous dummy variables. Daily returns of ten euro area stock indices from 4th January 2016 to 31th December 2020 has been used for the analysis. The results reveal that euro area stock markets respond differently to the COVID-19 pandemic. Specifically, the first wave of COVID-19 infections had a notable impact on stock market volatility of euro area countries with large and middle financial centres while the second wave had a significant impact only on stock market volatility of Belgium.

Research found that those who believe sexual orientation is inborn have generally positive attitudes towards gay men and lesbians. However, other studies have also found that these beliefs could include negative eugenic ideas. This study aims to investigate the role of people’s beliefs about the aetiology of sexual orientation on attitudes towards adoption for both gay and lesbian couples. We hypothesized that this relationship would be mediated by sexual prejudice. To test the predictions, 256 Italian heterosexual participants were asked to answer to a scale about their beliefs regarding the aetiology of sexual orientation, sexual prejudice, and attitudes towards adoption by same-sex couples. Results confirmed that the relationship between aetiology beliefs and adoption support was fully mediated by sexual prejudice. These investigation results suggest that the belief that sexual orientation is controllable may serve to justify one’s prejudice and, in turn, result in a lower support for same-sex couples’ adoption.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Microbes have evolved many fascinating and complex ways of interacting with conspecifics. Perhaps one of the most interesting is aggregative multicellularity, wherein independent cells come together and adhere to one another in order to form a larger entity. The fundamental benefits of active aggregation into multicellular groups generally remain unclear, and there are many open questions about what selective pressures led to the evolution of this behavior in various eukaryotic and prokaryotic taxa, most notably the dictyostelids and the myxobacteria. Aggregative multicellularity can be partitioned into three main phases: coming together, staying together as a group, and disaggregation. Different selective pressures may have led to adaptations unique to each phase. While aggregative microbial systems generally form elevated multicellular structures such as fruiting bodies, these can vary in complexity and morphology even among closely related species. What evolutionary forces shaped such morphological diversification remains unknown. Strains that are not genetically identical can coaggregate, which can impact group-level function either positively through functional synergy or negatively through harmful exploitation. Such chimerism within aggregates is likely to have played important roles in shaping the evolution of microbial multicellularity. Much further research is needed into the evolutionary forces and processes leading to and shaping the many forms of microbial aggregation.

Background: Tibial shaft fractures are the most common of long bone fractures. The gold standard for management is locked intramedullary nailing. The freehand method under fluoroscopic monitoring is the most often utilized method for distal screw locking. Electromagnetic guidance-based distal screw locking methods have gained popularity recently. The study's objective is to evaluate the system using electromagnetic tracking data against the free-hand technique. Methods: Sixty-three patients who received intramedullary nailing for tibial shaft fractures at our institute between January 2018 and May 2022, were included in this study. Two groups of patients were distinguished: Group FH underwent freehand distal locking and intramedullary nailing, while Group SS underwent electromagnetically guided locking. Radiation exposure period, as well as dose area product, were noted and statistically compared. Results: In terms of dose area product, a mean value of 43.57±31.57 cGy/cm2 in group FH and a mean value of 27.62±11.20 cGy/cm2 in group SS (p &lt; 0.05) was assessed. Concerning the duration of surgery a mean value of 128.83±26.51 minutes was reported in group FH and a mean value of 126.42±48.31 minutes in group SS (p &gt; 0.05). Conclusions: This study confirms the use of electromagnetic-guided locking distal screws reduces the total time of exposure to ionizing radiation, with no difference in operating time.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Since association between myocardial infarction (MI) and respiratory infections has been described for influenza-viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. First data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss: pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; what emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.

The Urban Heat Island (UHI) is one of the more serious consequences of urbanization resulting in impacts on thermal comfort levels, heat stress, and even mortality. For Municipal Beirut, implementation of “cool” surface materials and green spaces have been recommended to counterbalance the UHI. This paper builds on previous findings on the topic of non-constructible parcels within the district of Bachoura in Municipal Beirut and examines the possibility of implementing “cool” surface or paving materials and urban vegetation which can improve thermal conditions especially during the summer period and with the viewto project the positive findings of this case study to the entire Municipal Beirut area. A numerical analysis using ENVI-met 4.0 investigates the thermal performance of these non-constructibles further to implementation of high reflective surfaces and urban vegetation within a broad neighborhood scale in Bachoura. Results show reductions in ambient temperatures up to 1K on a summer day.. Within the framework of an integrated approach to planning, this form of urban acupuncture aims for substantial UHI reduction. Energy performance of buildings further to implementation of these mitigation measures is also recommended for future studies and to validate the findings in this paper.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Li⁺-conducting polyethylene oxide-based membranes, incorporating the N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide, are as electrolyte separators for all-solid-state lithium polymer batteries operating at medium-high temperatures. The incorporation of the ionic liquid remarkably improves the thermal, ion-transport and interfacial properties of the polymer electrolyte, which, in combination with the wide electrochemical stability even at medium-high temperatures, allow high current rates without any appreciable lithium anode degradation. Battery tests carried out at 80 °C have shown excellent cycling performance and capacity retention even at high rates, never tackled by ionic liquid-free polymer electrolytes. No dendrite growth onto the lithium metal anode was observed.

It was for long time believed that lidar systems based on the use of high-repetition micro-pulse lasers could be effectively used to only stimulate atmospheric elastic backscatter echoes, and thus only exploited in elastic backscatter lidar systems. Their application to stimulate rotational and roto-vibrational Raman echoes, and consequently their exploitation in atmospheric thermodynamic profiling, was considered not feasible based on the technical specifications possessed by these laser sources until a few years ago. However, recent technological advances in the design and development of micro-pulse lasers, presently achieving high UV average powers (1-5 W) and small divergences (0.3-0.5 mrad), in combination with the use of large aperture telescopes (0.3-0.4 m diameter primary mirrors), allow to presently develop micro-pulse laser-based Raman lidars capable to measure the vertical profiles of atmospheric thermodynamic parameters, namely water vapour and temperature, both in daytime and nighttime. This paper is aimed at demonstrating the feasibility of these measurements and at illustrating and discussing the high achievable performance level, with a specific focus on water vapour profile measurements. The technical solutions identified in the design of the lidar system and their technological implementation within the experimental setup of the lidar prototype are also carefully illustrated and discussed.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

As a hazardous waste, pickling waste liquor must be properly treated. An alternative consists in promoting the formation of ferrous salts from this residue, due to its higher ferrous content. Since FeCl2·4H2O is widely used in several applications, obtaining pure crystals of this material appears to be an interesting prospect. However, this compound has scarcely been investigated. In the present work, FeCl2·4H2O crystals have been obtained from pickling waste liquors. Their structural and morphological characteristics have been investigated by X-ray diffraction, scanning electron microscopy as well as Mössbauer spectroscopy. In addition, the photoluminescence study of the obtained samples was also assessed. It was observed that after some aging time, the obtained crystals change in colour from green to more yellowish. So, the aged sample has also been evaluated, and their structural characteristics are compared with the original crystals. Despite this, the obtained crystals exhibit a FeCl2·4H2O structure, which is not modified with the aging of the sample.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

Orificed Hollow Cathodes are electric devices necessary for the functioning of common plasma thrusters for space applications. From their reliability mainly depends the success of a spacecraft’s mission equipped by electric propulsion. The development of plasma models is crucial in the evaluation of plasma properties within the cathodes that are difficult to measure due to the small dimensions. Many models, based on non-linear system of plasma equations, have been proposed in the open literature. These are solved commonly by means of iterative procedures. This paper investigates the possibility to solve them by means of Particle Swarm Optimization method. The results of the validation tests confirm the expected trends for all the unknowns; the confidence bound of the discharge current as function of mass flow rate is very narrow (2÷5V), moreover the results match very well the experimental data except at the lowest mass flow rate (0.08mg/s) and discharge current (1A), where the computations underpredict the discharge current to the utmost by 40%; the highest data dispersion regards the plasma density in the emitter region (± 20 % of the average value) and the wall temperatures (± 50K respect to the average values) of orifice and insert; those of the others variables are very tiny.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

Purpose: to assess any differences on marginal bone loss between bone-level or tissue-level dental implants through a review of literature until September 2019. Materials and methods: MEDLINE, Embase and other database were searched by two independent authors. The search was limited to articles in English. Results: The search provided 1028 records and, after removing the duplicates through titles and abstracts screening, 45 full-text articles were assessed for eligibility. For qualitative analysis 20 articles were included, 17 articles of them for quantitative analysis. A total of 1161 patients (mean age 54,4 years) and 2933 implants were observed, 1427 (Tissue-level) and 1506 (Bone-level). The survival rate and the success rate were more than 90%, except for 2 studies with a success rate of 88% and 86.2%. No studies reported any differences between groups in term of success and survival rates. Three studies showed that BL-implants had statistically less marginal bone loss (P< 0.05). Only one study reported statistically less marginal bone loss in TL-implants (P< 0.05). In the most part of the studies, differences between implant types in marginal bone loss were not statistically significant. Conclusion: Despite to the peri-implant tissue around transmucosal implants has been reported to be inflammation-free because of the absence of bacterial infiltration in the micro-gap between the fixture and abutment, no clinical and radiological differences were highlighted between groups from the included studies after a variable period of follow-up ranged between 1 to 5 years.

The emergence of new methodologies and tools for digitizing objects belonging to the Cultural Heritage (CH) changed the paradigms adopted so far. Traditionally, the process to acquire artifacts required specialized and often costly equipment tailored to specific purposes. However, the development of more generalized, adaptable, and affordable tools led to novel approaches. This manuscript provides a glimpse into the evolving landscape of custom-made tools for digital documentation, both hardware and software, and their transformative impact on the digitization techniques, built to meet requirements of specific case studies, including ancient drawings, manuscripts, paintings, and museum objects. The advent of self-built instruments has revolutionized the way professionals work today, by leveraging a new generation of low-cost, adaptable gears, leading to unprecedented flexibility and efficiency, while facilitating the capture of high-quality digital representations of objects with minimal damage and preserving their integrity. The outcomes of instruments and tools specifically produced for the contexts described in this paper highlight their potential for promoting interdisciplinary collaboration, facilitating scholarly research, enhancing conservation efforts, and fostering cultural exchange. Ultimately, this research contributes to illustrate how custom software, in combination with recent devices such as smartphones and 3D printers, underscores the importance of adopting these innovative approaches to generate an ecosystem of tools and methods able to preserve, document, and promote the richness of our collective past for future generations.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecules detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combine both molecular filtering and molecular capture capabilities for biosensing applications. Along this line short oligonucleotide detection in a displacement assay is set within PEGDA hydrogels synthetized by UV radical photopolymerization. To provide insights on the molecular filter capability, diffusion studies of several probes (sulforhodamine G and dextrans) with different hydrodynamic radii were carried out using NMR technique. Moreover, fluorometric analyses of hybridization of DNA oligonucleotides inside PEGDA-hydrogels shed light on the mechanisms of recognition in 3D, highlighting that mesh size and crowding effect greatly impact of hybridization mechanism onto polymer network. Finally, we found the best probe density and diffusion transport conditions to allow the specific oligonucleotide capture and detection inside PEGDA-hydrogels for oligonucleotide detection and the filtering out of higher molecular weight molecules.

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Stress is a natural yet potentially harmful aspect of human life, necessitating effective management, particularly during overwhelming experiences. This paper presents a scoping review of personalized stress detection models using wearable technology. Employing the PRISMA-ScR framework for rigorous methodological structuring, we systematically analyzed literature from key databases including Scopus, IEEE Xplore, and PubMed. Our focus was on biosignals, AI methodologies, datasets, wearable devices, and real-world implementation challenges. The review presents an overview of stress and its biological mechanisms, details the methodology for the literature search, and synthesizes the findings. It shows that biosignals, especially EDA and PPG, are frequently utilized for stress detection and demonstrate potential reliability in multimodal settings. Evidence for a trend towards deep learning models was found, although the limited comparison with traditional methods calls for further research. Concerns arise regarding the representativeness of datasets and practical challenges in deploying wearable technologies, which include issues related to data quality and privacy. Future research should aim to develop comprehensive datasets and explore AI techniques that are not only accurate but also computationally efficient and user-centric, thereby closing the gap between theoretical models and practical applications to improve the effectiveness of stress detection systems in real scenarios.

Background: Recent advances allow the usage of Augmented Reality (AR) for many medical procedures. We perform different AR-assisted knee surgery techniques using optical surgical navigation with ArUco-type artificial marker sensors. Our study aimed to evaluate the system’s accuracy using an in vitro protocol. We hypothesised that the system’s accuracy was equal to or less than 1mm and 1° for distance and angular measurements, respectively. Methods: Our research was an in-vitro laboratory with a 316 L steel model. We evaluated absolute reliability according to the Hopkins criteria with seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. Results: The accuracy of the system to assess distances had a mean error of 1.203mm and an un-certainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observer almost perfect or perfect. Conclusions: The mean error for the distance’s determination has been statistically larger than 1mm (1.203mm) but with a trivial effect size. The mean error assessing angular values was sta-tistically minor than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Background: The surgical approach to treating calcaneal fractures, specifically Sanders types II, III, and IV, is still a subject of controversy. The decision to opt for open reduction and internal fix-ation (ORIF) or minimally invasive osteosynthesis (MIOS) remains uncertain owing to varying complication rates. This study intends to examine each treatment’s pros and cons in relation to the incidence of complications. Methods: In this retrospective study, we examined 70 patients treated between January 2018 and September 2022: 50 received ORIF, and 20 underwent MIOS. We evaluated functional outcomes with the Maryland Foot Score and the Creighton-Nebraska Health Foundation Assessment Scale (CNHFAS). We also assessed the amount of anatomical restoration using Böhler’s and Gissane’s angles, determined by radiographic checks, and the frequency of postoperative complications. Results: A significant reduction in the risk of reinter-vention was observed in patients with high anesthetic risks, polytraumatized individuals, and those with comorbidities who underwent MIOS. The chi-square test analysis of postoperative complications highlighted no substantial differences between the ORIF and MIOS groups in rela-tion to tendinitis, chronic pain and swelling, algodystrophy, and surgical wound infections (p > 0.20 for all). Conclusion: ORIF is more suitable for patients who have high motor function re-quirements, a long-term activity schedule and can endure potential additional procedures. This preference is because ORIF provides better anatomical restoration and features a lower osteoar-thritis occurrence rate.

This study describes the design and development of novel compounds aimed at optimizing the function of microtubules and tubulin in the immune system and the brain as they relate to the Orch OR theory of consciousness. These compounds are defined by the following molecular formulas:C65H100CoN15O22P(C6H12O5);C65H100CoN15O22P(C5H10NO4);(C65H100CoN15O22P)(C6H12N2O)n;(C65H100CoN15O22P)(C6H12O5)(C6H12N2O)n;(C6H12N2O)n(C6H12O5)m;Zn(C6H12O5)2;These molecules, formulated under the form of drugs, health functional foods, or food supplements, have the potential to positively affect a number of areas ranging from prevention and therapy of neurological diseases to supporting the immune system.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

We present a numerical illumination model to calculate direct as well as diffuse or Hapke scattered radiation scenarios on arbitrary planetary surfaces. This includes small body surfaces such as main belt asteroids as well as e.g. the lunar surface. The model is based on the raytracing method. This method is not restricted to spherical or ellipsiodal shapes but digital terrain data of arbitrary spatial resolution can be fed into the model. Solar radiation is the source of direct radiation, wavelength-dependent effects (e.g. albedo) can be accounted for. Mutual illumination of individual bodies in implemented (e.g. in binary or multiple systems) as well as self-illumination (e.g. crater floors by crater walls) by diffuse or Hapke radiation. The model is validated by statistical methods. A χ2 test is undertaken to compare simnulated images with DAWN images acquired during the survey phase at small body 4 Vesta.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

In this article, we consider the relationship between the brain and the immune system in the context of the Orch OR (Orchestrated Objective Reduction) theory of consciousness. Orch OR is a theory that postulates that consciousness arises from quantum computations occurring inside microtubules. The immune system is capable of acquiring, learning, and remembering information, thus showing all the attributes of natural intelligence. We argue that the immune system also has the attribute of consciousness and can gain access to an amount of information greater than what is accessible to the brain since it is not constrained by brain's reducing valve that is responsible for cognitive bottlenecks. We also describe the role of meditation and religious chanting in affecting the brain and immune system. We speculate that some effects of religious chanting on the immune system may not be mediated by the brain. Finally, we examine the role of the immune system in connecting with the consciousness embedded in the universe.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Variable-Angle Tow (VAT) laminates can improve straight fiber composites mechanical properties thanks to the application of curvilinear fibers. This characteristic allows to achieve ambitious objectives for design and performance purposes. Nevertheless, the wider design space and the higher number of parameters result in a more complex structural problem. Among the various approaches that have been used for VATs study, Carrera’s Unified Formulation (CUF) allows to obtain multiple theories within the same framework, guaranteeing a good compromise between the results accuracy and the computational cost. In this article, the linear buckling behavior of VAT laminates is analyzed through the extension of CUF 2D plate models within the Reissner’s Mixed Variational Theorem (RMVT). Results show that RMVT can better approximate the prebuckling non-uniform stress field of the plate when compared to standard approaches, thus improving the prediction of the linear buckling loads of VAT composites.

Driven by the growing interest of the scientific community and the proliferation of research in this field, cranial implants have seen significant advancements in recent years regarding design techniques, structural optimisation, appropriate material selection and fixation system method. Custom implants not only enhance aesthetics and functionality but are also crucial for achieving proper biological integration and optimal blood irrigation, critical aspects in bone regeneration and tissue health. This research aims to optimize the properties of implants designed from triply periodic minimal surface structures. The gyroid architecture is employed for its balance between mechanical and biological properties. Experimental samples were designed varying three parameters of the surface model: cell size, isovalue and shape factor. Computational simulation tools were used for determining the relationship between those parameters and the response variables: the surface area, permeability, porosity and Young modulus. These tools include computer aided design, finite element method and computational fluid dynamics. With the simulated values, the corresponding regression models were fitted. Using the NSGA-II, a multi-objective optimisation was carried out, finding the Pareto set which includes surface area and permeability as targets, and fulfil the constraints related with the porosity and Young modulus. From these non-dominated solutions, the most convenient for a given application was chosen, and an optimal implant was designed, from a patient computed tomography scan. An implant prototype was additively manufactured for validating the proposed approach.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

The Dead Sea basin is the lowest terrestrial site on the globe and is internationally recognized as a photoclimatotherapy center. Since the last century, questions raised regarding the possible presence of a unique incident ultraviolet irradiation, allowing successful treatment of psoriasis, atopic dermatitis and other dermatological diseases. Aim: Determine the characteristics of the solar ultraviolet irradiation and understand the mechanism of action of photoclimatotherapy while applying the results to clinical protocols of treatment. Methods: A meteorological station was established at the Dead Sea basin to continuously measure global, UVB and UVA irradiation. The same irradiation parameters are also being monitored continuously by a set of identical ultraviolet irradiation instruments installed on the campus of the Ben-Gurion University of the Negev, in Beer Sheva. Results: This study details the results of these long-term measurements, ae well as their correlation with the success obtained by clinicians treating psoriasis patients. Conclusions: A database of more than 25 years has enabled the medical staff to establish tailor-made protocols for sun-exposure time intervals as a function of particular month and hour of day. The availability of such information has significantly improved the results of photoclimatotherapy for psoriasis and at the same time increasing the safety of sun-exposure at the Dead Sea.

In this paper we investigate the geometric structure and control of exponential families depending on additional parameters, called external parameters. These generalized exponential families emerges naturally when one applies the maximum entropy formalism to derive the equilibrium statistical mechanics framework. We study the associated statistical model, compute the Fisher metric and introduce a natural fibration of the parameter space over the external parameter space. The Fisher Riemannian metric allows to endow this fibration with an Ehresmann connection and to study the geometry and control of these statistical models. As an example, we show that horizontal lift of paths in the external parameter space corresponds to an isentropic evolution of the system. We apply the theory to the example of a ideal gas in a rotating rigid container. Most of the results are expressed in local coordinates; in the appendices we hint at possible global extensions of the theory.

The increasing demand for higher inclusion cleanliness levels motivates the control over the formation and evolution of inclusions in the steel production process. In this work, the evolution of the chemical composition and size distribution of inclusions throughout a slab production process of Al-killed steel, including ladle furnace (LF) treatment and continuous casting (CC), was followed. The initial solid Al2O3 and Al2O3-MgO inclusions were modified to liquid Al2O3-CaO-MgO inclusions during LF treatment. The evolution of the size distributions during LF treatment was associated with the growth and removal of inclusions, as new inclusions were not created after the deoxidation process, according to a population density function (PDF) analysis. Additionally, the size distributions tended to be similar as the LF treatment progressed regardless of their initial features, whereas they differed during CC. Analysis of the upper tails of the distributions through generalized extreme values theory showed that inclusion distributions shifted from larger to smaller sizes as the process progressed. There were great changes in the distributions of large inclusions throughout the LF treatment and between the end of the LF treatment and the start of the CC process. Additionally, distributions of large inclusions differed at the end of the LF treatment, whereas such differences decreased as CC progressed.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

During a sanitary crisis, excess mortality measures the number of all-cause deaths, beyond what we would have expected if that crisis had not occurred. The high number of COVID-19 deaths started a debate in Italy with two opposite positions: those convinced that COVID-19 deaths were not, by default, excess deaths, because many COVID-19 deaths were not correctly registered, with the most part attributable to other causes and to the overall crisis conditions, and those who presented the opposite hypothesis. We analyzed the curve of the all-cause excess mortality, during the period January 5, 2020 – August 28, 2022, compared to the curve of the daily confirmed COVID-19 deaths, investigating the association between excess mortality and the recurrence of COVID-19 waves in Italy. We compared the two curves looking for the corresponding highest peaks and we found that 5 out of the 6 highest peaks (83.3%) of the excess mortality curve have occurred, on average, just a week before the concomitant COVID-19 waves hit their highest peaks of daily deaths (Mean 6.4 days; SD 2.4 days). This temporal correspondence between the moments when the excess mortality peaked and the highest peaks of the COVID-19 deaths provides further evidence that the all-cause excess mortality wave has been mostly driven by COVID-19 deaths

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Augmented Reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications is driving new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify the value and impact in the medical-scientific field especially in the improvement of diagnostic in complex fractures. Acetabulum fractures have always been a challenge among orthopedics, for volumetric complexity and low diagnostic reliability.Background/Objectives: The goal of this study is to determine whether these methods can improve the learning aspect and diagnostic accuracy of complex acetabulum fractures compared to gold standard CT (computed tomography). Methods: Orthopedic residents of our department have been selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum have been included in the study, obtaining : CT-scans, 3DP model, and AR model displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture according to methods. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: 20 residents (JUN=10, SEN=10) classified five fractures. Overall DAs were 26% (CT), 18% (3DP), and 29% (AR). AR-DA resulted to be superior to 3DP-DA (p=0,04). DA means (JUN vs SEN respectively) were :CT-DA was 20% vs 32% (p&lt;0.05), 3DP-DA was 12% vs 24% (p=0.08), and AR-DA was 28% vs 30% (p=0,80). Overall RT was 61.2 sec (±24,6) for CT, 35.8 sec (±20,1) for 3DP, and 46,7 sec (±20,8) for AR. R was fairly poor between methods and groups. 3DPs resulted to have superior overall C (65%). Conclusions: AR resulted to have the same Overall DA as CT, independent from experience, 3DP has minor DA and R, but it resulted to be the most confident and fast method. Intra and interobserver R between methods remain very poor in residents.

This article describes a novel topical composition constituted by gamma-amino butyric acid (GABA) and microbial chondroitin sulfate. This composition, formulated by the author and manufactured in a certified facility in the United States of America, exhibits potential for non-invasive intervention in anxiety management, sleep quality enhancement, and promotion of brain-related functions like meditation and nonlocal consciousness. The core component comprises GABA, a key inhibitory neurotransmitter within the central nervous system, complexed with a suitable carrier molecule, microbial chondroitin sulfate. This complexation aims to enhance transdermal absorption and optimize delivery of GABA to target tissues. The proposed mechanism of action involves modulation of GABAergic signal transduction pathways. Application of the topical composition allows GABA penetration into the skin and potentially deeper tissues, where it interacts with GABA receptors. This interaction leads to mental calmness and relaxation as assessed by electroencephalography. The influence of GABAergic signaling on brain circuits demonstrated in this article, when associated with meditation and nonlocal consciousness, suggests potential for the composition to support these practices. The advantage of such an approach consists in avoiding the potential systemic side effects associated with oral or injectable administration of GABA, anxiolytics or hypnotics. Furthermore, the combination of GABA and microbial chondroitin sulfate may offer synergistic benefits, potentially enhancing the overall biological effects. In conclusion, this article presents a novel topical approach for managing anxiety, enhancing sleep quality, and potentially facilitating meditation and nonlocal consciousness through modulation of GABAergic signaling pathways. While further research is necessary, the potential for a non-invasive and potentially side-effect-free intervention in these areas is promising.

Sinkhole flooding is an essential hydrological process to recharge karst aquifer in arid to dry sub-humid regions. On the other hand, the increase of rain extremes is one of the major consequences of the global warming, together with the expansion of drylands. Thus, appropriate runoff regulation in endorheic karst basins in order to reduce the risk of flooding and improve the quantity and quality of the water drained by sinkholes will be more and more crucial. With these premises, a systematic review was performed by using WoS engine to infer the best practices for the karst water management in regions actually or potentially affected by water scarcity. Hydrological models are essential to manage the consequences of climate change on karst water resource, however the review shows that providing the tools necessary for reliable modeling is still challenging. Finally, due to the intrinsic vulnerability of the karst aquifers, pollution reduction and wastewater recycling policy will play key role in the next decades.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Coaxial rotors can be found in multirotor vehicles for the added thrust compared to independent rotors while keeping similar area footprints but, performance losses should be considered. This experimental study analyzes the effects of varying motor throttle and propeller pitch values in motor-propeller systems with two to four coaxial rotors. The results show that in a two-rotor coaxial system, to lessen the adverse effects of a front rotor’s backwash and to operate at the maximum performance, only the back motor should be operated initially up to 75% duty cycle before using the front motor up to its 75% duty cycle. Additional thrust requirements should be generated from the back rotor and then from the front rotor up to their maximum duty cycles. In two, three, and four-rotor coaxial setups, total thrust output generated is 1.6, 2.1, and 2.5 times the thrust output at system thrust performance of 86%, 76%, and 66%, respectively of that of an isolated rotor. In a four-rotor coaxial setup, maximum system performance is achieved when the propeller pitch values are gradually increased from the first to the last rotor. The gradual increments in propeller pitch values also result in more uniform thrust sharing among rotors.

High efficacy LED lamps combined with adaptive lighting control and greenhouse integrated photovoltaics (PV) could enable the concept of year-round cultivation and become a feasible option even in the harsh climate of the Nordic countries. Meteorological satellite data of this region was analyzed in a parametric study to evaluate the potential of these technologies. The generated maps showed monthly average temperatures fluctuating from -20°C to 20°C throughout the year. The natural photoperiod and light intensity also changed drastically, resulting in monthly average daily light integral (DLI) levels ranging from 45-50 mol·m-2·d-1 in summer and contrasting with 0-5 mol·m-2·d-1 during winter. To compensate, growth room cultivation independent from outdoor conditions could be used in winter. Depending on the efficacy of the lamps, the electricity required for sole-source lighting at 300 µmol·m-2·s-1 for 16 hours would be between 1.4 and 2.4 kWh·m-2·d-1. Greenhouses with supplementary lighting could help start the cultivation earlier in spring and extend it further into autumn. The energy required for lighting highly depends on several factors such as the natural light transmittance, the light threshold settings and the lighting control protocol, resulting in electric demands between 0.6 and 2.4 kWh·m-2·d-1. Integrating PV on the roof or wall structures of the greenhouse could offset some of this electricity, with specific energy yields ranging from 400 to 1120 kWh·kWp-2·yr-1 depending on the region and system design.

We studied the weekly number and the growth/decline rates of COVID-19 deaths in the period October 31, 2022 – February 9, 2023, in Italy, finding that that COVID-19 winter wave reached its peak during the three holyday weeks extending from December 16, 2022 to January 5, 2023, and it was definitely trending downward, returning to the same number of deaths of the end of October 2022, in the week February 3 – 9, 2023. During this period of fifteen weeks, that wave caused a number of deaths as large as 8,526. Its average growth rate was +7.89% deaths per week (ten weeks), while the average weekly decline rate was -12.32% (five weeks). Currently, Italy is experiencing a new COVID-19 wave, with the latest six weekly bulletins (October 26, 2023 – December 14, 2023) showing that the deaths have climbed from 148 to 322. The weekly growth rate has risen by +14.08% deaths, on average. In the hypothesis that this 2023-2024 wave have a duration similar to that of 2022-2023, with: i) a comparable extension of both the growing period and of the decline period and ii) similar growth/decline rates, a prediction can be cast regarding the number of COVID-19 deaths in the period November 2023 - January 2024. They could reach the amount of 4100-4200

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Recent evidence obtained in murine atrial cardiomyocytes suggests that the behavior of tubulin, a constituent of microtubules, is influenced by audible sounds. In the present study, the sequence and the structure of murine and human tubulins were compared with those of human TMC1 (Transmembrane channel-like protein 1), a sound-sensitive protein that is responsible for forming the pore of mechanosensory transduction channels in the hair cells of the inner ear of vertebrates, and with those of bacterial FtsZ (Filamenting temperature-sensitive mutant Z), a bacterial protein homologous to tubulin. The results show that mouse and human alpha-tubulin are 100% identical, whereas sequence homology of human TMC1 and human tubulin alpha 1A chain is scarce, with only 17.31% identity. A higher degree of similarity was observed in the presence of aromatic amino acids as well as in the propensity to form alpha-helices. Based on these results, it is hypothesized that the response of tubulin to audible sounds is mediated by the external alpha-helices as it occurs in TMC1. The sequence homology of human TMC1 and FtsZ from Lactobacillus johnsonii, is moderate with 23.40% identity, however higher than that between TMC1 and tubulin. The overall presence of aromatic amino acids in FtsZ is scarce, but helix propensity is significant. These results are discussed in the context of Orch OR, a theory that postulates that consciousness emerges from quantum computations occurring in microtubules of neurons via information processing mediated by aromatic amino acids of tubulin.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Landward displacement of coastal boulders is a morphodynamic signature of inundation and erosion processes. The study of these movements can provide useful elements for coastal hazards assessment. In this note, using open-access remote sensing resources, the 2017 to 2021 annual mobility of medium, coarse, and very coarse boulders spread over about 100 km of the eastern coast of the Gulf of Taranto (Italy) is detected. A large interannual variability was found. As established by multi-temporal object-based image analysis, one hundred and ten boulders changed position between July 2019 and June 2020, no boulder was displaced between July 2017 and July 2018, and few boulders were displaced between July 2018 and July 2019, and June 2020 and September 2021. A hydrodynamic analysis of the investigated boulder displacement led to the estimation of the energy of nearshore waves that hit the coast. The storm Detlef, that crossed over the Mediterranean Sea during 11-13 November 2019, is presumed to be the main cause of the massive displacement phenomenon.

We present here a five hours experimentation of a didactical path about the electromagnetic induction addressed to students of the last year of an Italian scientific high school and oriented to better understand the physical origin of the induced electromotive force. The expression of the induced electromotive force as the sum of the term linked to the time variation of the magnetic field and of the motional one has been obtained in a detailed way, still suitable for presentation at high school. Many examples have been proposed to the students in order to clarify the conceptual physical knots. The students’ responses to a 6-questions multiple choice questionnaire have been analyzed. It emerged that our approach is concretely feasible although we find the well-known difficulties in calculating flux and circulation of a vector field. Furthermore, it emerged that an integral approach to the problem masks the understanding of the nature of the forces acting locally on the charges. Hence our proposal of a “redefinition” of the induced electric field in terms of the magnetic vector potential is also presented.

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

In Nitrate Vulnerable Zones (NVZ) site-specific techniques are needed to match N availability with durum wheat (Triticum turgidum subsp. durum Desf.) requirements. Enhanced-efficiency fertilizers (EEF) can improve efficient N supply and reduce leaching, thus contributing to sustainable agriculture. To study the effects of rates, sources and timings of nitrogen application, two-year field experiments were carried out at two Mediterranean NVZs of Central Italy (Pisa and Arezzo). The trial compared: i) two N rates: one based on the crop N requirements (NO), the other on the Action Programmes’ prescriptions of the two NVZ (NAP); ii) three N sources (urea, methylene urea (MU), and nitrification inhibitor (NI) 3,4-Dimethylpyrazole phosphate (DMPP); and two top-dressing timings (1st tiller visible and 1st node detectable). Grain yield and yield components were determined, together with N uptake. Results showed that: i) grain and biomass production were reduced with NAP at both locations; ii) urea performed better than slow-release fertilizers; iii) the best application time varied depending on N source and location: at Pisa enhanced-efficiency fertilizers achieved higher yields when applied earliest, while for urea the contrary was true; at Arezzo different N fertilizers showed similar performances between the two application timings. Different behaviors of top-dressing fertilizers at the two localities could be related to the diverse patterns of temperatures and rainfall. Therefore, optimal fertilization strategies vary according to environmental conditions.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from April 2021 to May 2023 were retrospectively collected and analyzed according to age groups and vaccination status and the Standardized Mortality Ratio (SMR) for all-cause mortality and for non-COVID-19 were calculated in comparison to the corresponding unvaccinated groups. Results show that, since an age group dependent date, the all-cause mortality SMRs were increasing in any of the age groups considered. Initially, the all-causes death SMRs were less than 1 for all age groups, but due to their growth, for the age groups 18-39, 80-89 and 90+ years by a certain date they exceeded the reference value. For the other age groups, as long as the trend is maintained, it is possible to predict the date in which the SMR would reach the value 1. Non-COVID-19 SMR values show a very similar trend. Their initial values much lower than 1 suggest the presence of significant biases in the ONS dataset which lead to an underestimation of the risks for those vaccinated, as it is not plausible that the vaccine protects from causes other than COVID-19. The finding that all-cause mortality SMRs in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and should be implemented a moratorium of the promotion of mass vaccination campaigns.

Compressive residual stresses in thin films can inhibit crack propagation under normal or sliding contact loading, with associated enhancement of the coating apparent toughness, load bearing capacity and wear resistance. This study investigates the influence of residual stress distributions on the thin film/substrate adhesion using a nanoindenter coupled with scanning electron microscope (SEM) investigations of indentation induced failure modes. Reactive and un-reactive magnetron sputtering with ion plating was used to coat a (100) silicon substrate with aluminum nitride (AlN) with and without an aluminum (Al) adhesion layer. The presence of an Al bond layer gives additional interfacial tensile stress because of the difference in thermal expansion coefficient. Additionally, a different magnitude of residual stresses in the AlN coating was achieved by changing the applied bias voltage onto the substrate. Wafer curvature method and incremental focused ion beam (FIB) milling, combined with high-resolution in situ scanning electron microscopy (SEM) imaging and full field strain analysis by digital image correlation (DIC), were used to measure the average and in-depth stress residual stress distribution in the produced coatings. The adhesion energy was then quantified by using a nanoindentation based model. Results demonstrate that the additional tensile residual stress in the aluminum adhesion layer decrease significantly the coating adhesion, even in presence of a higher compressive stress state in the AlN top-layer. Therefore, the coatings without Al-layer showed better adhesion because of a more homogeneous compressive residual stress in comparison with the coating having Al layer, even though both groups of coatings are produced under same bias voltage. Results are discussed, and some general suggestions are made on the correlation between coating/substrate property combination and the adhesion energy of multilayer stacks. The results suggested that Al bond-layer and inhomogeneous residual stresses affected the adhesion of AlN negatively to a substrate like silicon.

Spatio-temporal aspects of data lead to critical information. Sensors capture data at all scales continually so it is imperative that useful information be extracted ubiquitously and regularly. Location plays a vital part by helping understand relations between datasets. It is crucial to link developmental works with spatial attributes and current challenge is to create an open platform that manages real-time sensor data and provides critical spatial analytics atop expert domain knowledge provided in the system. That is a two-faced problem where the solution tackles not only data from multiple sources but also runs data management platform, a spatial data infrastructure(SDI) as backbone framework able to harness sensor web(SW). The paper proposes development of such a globally shared open spatial expert system(ES), SmaCiSENS, a first of a kind geo-enabled knowledge based(KB) ES for multiple fields, smarter cities to climate modeling. SmaCiSENS is integration of SW and SDI with domain KB on data and problems, ready to infer solutions. The paper describes an architecture for semantic enablement for SW, SDI; connect interfaces, functions of SDI and SW, and sensor data application program interfaces (APIs) to better manage climate modeling, geohazard, global changes, and other vital areas of attention and action.

In the digital age, Artificial Intelligence (AI) is emerging as a transformative force in various sectors, in-cluding medicine. This article explores the potential of AI, akin to the magical genie of Aladdin's lamp, particularly within thoracic surgery and lung cancer management. It examines AI applications like ma-chine learning and deep learning in achieving more precise diagnoses, preoperative risk assessment, and improved surgical outcomes. The challenges and advancements in AI integration, especially in computer vision and multi-modal models, are discussed alongside their impact on robotic surgery and operating room management. Despite its transformative potential, implementing AI in medicine faces challenges regarding data scarcity, interpretability issues, and ethical concerns. Collaboration between AI and medi-cal communities is essential to address these challenges and unlock the full potential of AI in revolution-izing clinical practice. This article underscores the importance of further research and interdisciplinary collaboration to ensure the safe and effective deployment of AI in real-world clinical settings.

This study investigates the microbial composition of a commercially available Swiss fermented milk and colostrum product with a history of use in chronic condition management since 2014. The analysis, performed using the Axiom Microbiome Array, identified a high number of targets corresponding to microbial species classified as probiotics belonging to the Bifidobacteriaceae family. The array provided 28 unique targets, each corresponding to a specific microbe. Next, the amino acid sequences of beta-galactosidase and sialidase from Bifidobacteria and humans were studied because these enzymes are responsible for the production of GcMAF (Gc protein-derived Macrophage Activating Factor) from the Gc protein that is abundant in colostrum. The Bifidobacterial enzymes showed striking functional similarities with their human counterparts. In addition, the study explores the potential health benefits of this product with a focus on GcMAF and chondroitin sulfate, a glycosaminoglycan highly represented in milk and colostrum. The high concentration of specific Bifidobacteria strains contributes to these benefits through two mechanisms: enhanced GcMAF production and activation of chondroitin sulfate, which in turn exhibits GcMAF-like activity. These findings suggest that the Bifidobacteria-rich Swiss product could offer health benefits through these combined mechanisms.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Gastric cancer is the fifth most common and fourth deadliest cancer worldwide, with a bleak 5-year survival rate of about 20%. Despite significant research into its pathobiology, prognostic predictability remains insufficient due to pathologists’ heavy workloads and the potential for diagnostic errors. Consequently, there is a pressing need for automated and precise histopathological diagnostic tools. This study leverages Machine Learning and Deep Learning techniques to classify histopathological images into healthy and cancerous categories. By utilizing both handcrafted and deep features and shallow learning classifiers on the GasHisSDB dataset, we conduct a comparative analysis to identify the most effective combinations of features and classifiers for differentiating normal from abnormal histopathological images without employing fine-tuning strategies. Our methodology achieves an accuracy of 95% with the SVM classifier, underscoring the effectiveness of feature fusion strategies. Additionally, cross-magnification experiments produced promising results with accuracies close to 80% and 90% when testing the models on unseen testing images with different resolutions.

The progression of the recent COVID-19 pandemic surprised political authorities as well as scientists. The possibility to design powerful strategies for health care and preserving economic and social activities strongly relies on the capacity to monitor correctly the virus spreading and the immune response in the symptomatic and asymptomatic population. The available data relative to the first pandemic months indicate that the test reliability was progressively improved but also that the extremely variable methodologies used in the diagnostic studies generated data that are often not comparable. This condition prevents a simple metadata analysis for the identification of reliable diagnostics guidelines. Nevertheless, there are converging evidences that combinations of complementary approaches may enable more precise identification of virus infection. Furthermore, it appears that the similarities between SARS-CoV2 and the related types SARS-CoV1 and MERS that caused outbreaks in the last 20 years can be exploited to infer some information for which no direct evidence is still available

Since the discovery of the first reported case with Zinc-deficiency in Iran¹ by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response ^2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency⁴. In the western world, Zinc deficiency is more prevalent among the geriatric population³, vegans/vegetarians, and people with certain underlying conditions⁴such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders^4,5. Zinc and Zinc deficiency has been associated with several infectious diseases ^2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21^st century^6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.

Growth hormone (GH) deficiency affects up to 1 in 4,000 children and is usually treated with daily injections of GH whilst the child is still growing. With children typically diagnosed around 5 years old, this can mean over 10 years of therapy, which can place a considerable burden on the child and parent. Over three-quarters of children are estimated to be not fully compliant with therapy, which can compromise their chances of attaining their target height. In recent years, interactive mobile health (smart phone or tablet) interventions using game-like concepts, so called ‘gamification’, have increased in popularity and have demonstrated success in promoting positive self-management behaviour in children with chronic conditions, such as diabetes. The application of gamified interventions has the potential to support adherence to therapy and positive behaviour in children with GH deficiency in a number of ways: 1) By providing education in a format that the child understands and accepts (e.g. using behavioural constructs to facilitate explaining why adherence is important); 2) By providing a mechanism to reduce the anxiety and stress associated with administering the injection (e.g. diversion with a virtual pet); and 3) By providing feedback to encourage on-going engagement (e.g. rewards, progression through levels).

This study examines the activities conducted at the archaeological site of Aptera in Crete, Greece. The research was part of the DIACHRONIC LANDSCAPES International Design Workshop, organized by the CAM (Center for Mediterranean Architecture), TUC (Technological University of Crete School of Architecture), and UNIFE (University of Ferrara Department of Architecture). This article outlines the methods used for data acquisition and processing on a territorial scale, which generated digital outputs necessary for the analysis and design phases of the workshop, as well as for further examination of the results. The collected data, obtained through low-cost aerial photogrammetric surveying and GNSS terrestrial coordinate detection, were integrated in a Structure from Motion workflow that led to the creation and exportation of various digital outputs, such as point clouds, DTM, DSM, orthophotos, and contour lines. An accuracy analysis was performed to evaluate the effectiveness and efficiency of the digital models compared to the implemented surveying strategies, including the Ground Control Point and Quality Check Point marker positioning strategy. The resulting digital models proved to be valuable assets for analysis and design within the workshop and provided insightful prospects for future research and territorial-scale projects.

Single-cell RNA sequencing (scRNA-seq) technology has significantly advanced our understanding of the diversity of cells and how this diversity is implicated in diseases. Yet, translating these findings across various scRNA-seq datasets poses challenges due to technical variability and dataset-specific biases. To overcome this, we present a novel approach that employs both an LLM-based framework and explainable machine learning to facilitate generalization across single-cell datasets and identify gene signatures to capture disease-driven transcriptional changes. Our approach uses scBERT, which harnesses shared transcriptomic features among cell types to establish consistent cell-type annotations across multiple scRNA-seq datasets. Additionally, we employ a symbolic regression algorithm to pinpoint highly relevant yet minimally redundant models and features for inferring a cell type’s disease state based on its transcriptomic profile. We ascertain the versatility of these cell-specific gene signatures across datasets, showcasing their resilience as molecular markers to pinpoint and characterize disease-associated cell types. Validation is carried out using four publicly available scRNA-seq datasets from both healthy individuals and those suffering from ulcerative colitis (UC). This demonstrates our approach’s efficacy in bridging disparities specific to different datasets, fostering comparative analyses. Notably, the simplicity and symbolic nature of the retrieved gene signatures facilitate their interpretability, allowing us to elucidate underlying molecular disease mechanisms using these models.

This study investigates the effects of chanting Nam-Myoho-Renge-Kyo on sound frequencies, brain activity, and microbial metabolism. Spectral analysis of chanting revealed peaks at 8 Hz and 116 Hz, corresponding to the first Schumann resonance and a frequency linked to chloride ion movements, respectively. Additionally, five peaks corresponding to solfeggio frequencies were identified. These frequencies are known to exert a positive impact on the human endocrine and autonomous nervous systems; improve survival of human brain cells; decrease anxiety in rats; reverse cognitive and endocrine deficits in zebra fish; reduce total concentration of reactive oxidative species in brain tissue. Brain activity changes were measured using functional near-infrared spectroscopy. Prefrontal cortex activity increased modestly during chanting compared to a pre-chanting baseline, but significantly increased afterwards. This suggests a shift towards focused attention during chanting and enhanced activity afterward. The study also examines the effects of chanting on microbial metabolism. Cultures exposed to chanting, either directly or indirectly, showed increased metabolic activity. This suggests local and non-local effects, similar to previously reported phenomena. Importantly, the study clarifies that the spiritual practice of Nichiren Shoshu Buddhism can't be reduced to mere neurophysiological mechanisms in the brain or any other part of the body. The religious and spiritual experience of practicing Buddhism and chanting Nam-Myoho-Renge-Kyo goes well beyond brain activity, neurotransmitters or quantum phenomena of consciousness. It encompasses a mystic dimension that, although not in contradiction with science, can’t be explained solely by science.

In the present paper, we efficiently solve the two-body problem for extreme cases such as those with high eccentricities. The use of numerical methods, with the usual variables, cannot maintain the perihelion passage accurately. In previous articles, we have verified that this problem is treated more adequately through temporal reparametrizations related to the mean anomaly through the partition function. The biparametric family of anomalies, with an appropriate partition function, allows a systematic study of these transformations. In the present work, we consider the elliptical orbit as a meridian section of the ellipsoid of revolution, and the partition function depends on two variables raised to specific parameters. One of the variables is the mean radius of the ellipsoid at the secondary, and the other is the distance to the primary. One parameter regulates the concentration of points in the apoapsis region, and the other produces a symmetrical displacement between the polar and equatorial regions. The three most used geodesy latitude variables are also studied, resulting in one not belonging to the biparametric family. However, it is in the one introduced now, which implies an extension of the biparametric method. The results obtained by the method presented here now allow a causal interpretation of the operation of numerous reparametrizations used in the study of orbital motion.

In recent years web applications and on-line business transactions have grown many folds. Consequently, also cyberattacks have increased and represent a serious threat to the pervasive digital services upon which our society relies. To mitigate cyberattacks, many countermeasures are deployed on computing nodes (e.g., anti-malware software) as well as on network devices to detect and possibly block malicious packets in transit; these monitoring devices broadly go under the name of firewalls. Firewalls are designed according to two main architectural approaches: software running on a standard or embedded computer, or purposedly designed hardware, e.g., ASICs. Software-based solutions have the advantage of high flexibility and can be ported on easily upgradable hardware. However, hardware implementation represents the only viable solution for high data rates. On the market, very fast devices of the latter kind are available, but their cost is typically very high, especially considering that their ultra-optimized design makes updating them very difficult, with the consequence of a rather short lifespan. As a more balanced alternative, we wanted to investigate the use of an FPGA architecture, , which is significantly easier to update than custom-built chips, and features low-latency and high-throughput characteristics concurrently, making it preferrable to other programmable systems based on GPUs or microcontrollers. In this paper a packet sniffer that has been designed on FPGA with a 1 Gbit/s data transfer rate is presented. The system is implemented on the FPGA development board KC705 by Xilinx, can analyze Ethernet frames, checking the frame fields against a set of rules defined by the user and calculates statistics of the received Ethernet frames over time. The designed packet sniffer has been successfully tested both with Ethernet frames ad hoc generated using a packets generator, and with real web traffic by connecting the packet sniffer to the internet.

The Volturno Plain is one of the largest alluvial plain of peninsular Italy. This area is characterized by both natural and human induced subsidence, and is and most susceptible to coastal hazards. The present study is based on post-processing, analysis and mapping of the available Persistent Scatterer interferometry datasets, derived from combination of both ascending and descending orbits of three different SAR satellite systems, during an observation period of almost two decades (June 1992 - September 2010). The main output of the research work is a map of the vertical deformation that provides new insights into the areal variability of ground deformation processes (subsidence/uplift) of Volturno plain over the last decades. Vertical displacement values derived by interferometric data post-processing show that the Volturno river plain is characterized by significant subsidence in the central axial sectors and in the river mouth area, whereas moderate uplift is detected in the eastern part of the plain. Other sectors of the study area are characterized by moderate subsidence and/or stability. We infer that the subsidence recorded in the Volturno plain is mainly a consequence of a natural process related to the compaction of the fluvial deposits that fill up the alluvial plain. Anthropic influence (e.g. water exploitation, urbanization) can be substantially regarded as an additional factor that only locally may enhance subsidence. The uplift imaged in the eastern sector of the plain can be related to tectonic activity. The study of subsidence in the Volturno plain is a valuable tool relevant for river flood analyses and coastal inundation hazard assessment addressed to risk mitigation.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.

Macrophages are well known for the involvement in the biocompatibility, as well as biodistribution, of nano(bio)materials. Although there are a number of rodent cell lines, they may not fully recapitulate primary cell responses; particularly for those of human cells. Isolation of tissue resident macrophages, from humans, is difficult and may result in insufficient cells with which to determine the possible interaction with nano(bio)materials. Isolation of primary human monocytes, and differentiation to monocyte-derived macrophages, may provide a useful tool with which to study, further, these interactions. To that end, we developed a standard operating procedure for this differentiation, as part of the REFINE project, and used it to measure the secretion of bioactive molecules from M1 and M2 differentiated monocytes in response to model nano(bio)materials, following an initial assessment of pyrogenic contamination which may confound, potential, observations. The SOP was deployed in two partner institutions with, broadly, similar results. The work presented here shows the utility of this assay but, highlights the relevance of donor variability in responses to nano(bio)materials. Whilst donor variability can provide some, logistical, challenges to application of such assays, this variability is much closer to the heterogeneous cells that are present in vivo, compared to homogeneous, non-human, cell lines.

This note makes available five years of data gathered in a measurement site equipped with a micrometeorological station and two monitoring wells. Series of data of hydrological and atmospheric variables allow to estimate the flux of water across the atmosphere-land interface and to calculate the water budget, that are crucial topics in climate and environmental sciences. The measures of water-table began during 2017, one of the driest year of the whole instrumental period of climate history for the Central Mediterranean. Data from the micrometeorological station have been used to construct two more datasets of daily and monthly cumulative values of different terms of the surface water budget, from which the groundwater infiltration has been estimated. A significant decreasing trend characterizes both the data time series of piezometric heights and estimated infiltration in the considered period. All the data are collected in 2017-2022 datasets that are available in the supplementary material.

This article proposes a particular strategy to proceed with a progressive electrification of public transport systems in cities. Starting from a bus operation model, the possible electrification of two routes is analysed, one urban and another extra-urban in the city of Pisa. An estimate is made of the energy uses associated with certain operating modes. The maximum level of consumption is estimated at approximately 280 kWh per day per bus for the urban route and excluding some special days, less than 215 kWh per day for the extra-urban route, for which a hybrid bus is proposed. Starting from an estimate of the daily consumption for the management of the two routes, the sizing of a photovoltaic system distributed on some modular shelters which serves to power the same routes is carried out. The resulting system has a power of the order of 190-200 kW. The modular solution is also outlined, and an installation is proposed. The analyzed case lends itself to being easily replicated.

Contaminants of Emerging Concern (CECs), a new category of contaminants in limelight, is a major issue of global concern. The pervasive nature of CECs and its harmful effects, such as cancer, reproductive disorders, neurotoxicity etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentration of CECs can cause great impacts on living beings. It also has a nature of bioaccumulation. Thus, it is the ultimate need to have efficient sensors for detection of CECs to ensure safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in literatures under each category for the detection of major CECs.

Several coastal barriers experienced significant erosion and change in shape throughout the Mediterranean coasts over the past decades, and the issue has become of increasing concern for scientists and policymakers. With reference to a case study and by meteorological and geomorphological investigations, this note aims to infer recent shoreline dynamics and define coastal phenomena shaping the beach-dune barrier of Cesine Lagoon (South Italy), to finally point out the weather-driven processes. A challenge for this research was to obtain significant results from publicly available sources and simple and inexpensive methods. The retreat of the dune toe, the accretion of washover fans, and the formation of gravel beaches have been related to the analyzed wind-wave conditions. Net longshore transport was found in accordance with the direction of the more intense winds. The role of extreme events in the shaping of coastal landforms is yet to be established even if they greatly increase the vulnerability to flooding of the study area. The results achieved so far are starting points for further data collection and analysis in the perspective of assessing the impact of climate changes on the lagoon barrier.

Magnesium is one of the lightest structural metal used in different industrial sector and many works are present in literature about the study of its reinforcement by fillers addition. Basalt fibres are natural fillers with good mechanical properties, excellent resistance to high temperature and lower cost than carbon fibres. For these aspects, in the last years they are increasingly used in the production of composite materials with polymeric matrices. However, very few information are presents in literature about the use of basalt fibres as reinforcement in metal matrix composite materials. It is well known that the impregnation of fibres reinforcement affects the mechanical behavior of composites materials. The aim of this study is to investigate the impregnation and the behavior of basalt fibres in a magnesium alloy composite material manufactured by a centrifugal casting technique.

This study deals with vibrational and crystallographic aspects of the thermally induced transformation of serpentine-like garnierite into quartz, forsterite, and enstatite occurring at about 620 °C. Powder specimens of garnierite have been annealed in static air between room temperature and 1000 °C. The resulting products from the transformations detected based on thermogravimetric and differential thermal analysis, have been extensively characterized via microRaman spectroscopy, and X-ray diffraction. Our study shows that serpentine-like garnierite consists of a mixture of different mineral species. Furthermore, these garnierites and their composition can provide details based on the mineralogy and the crystalline phases resulting from the thermal treatment.

Studying the dynamics of urban form means questioning the processes of evolution of the form in general. The discussion on the architecture of buildings and urban spaces has drawn the concept of adaptation from the theories of natural evolution. These notes propose a reflection on the opposite concept of exaptation proposed by the biologist and paleontologist Stephen Jay Gould in 1982. Through some examples (some different transformations of the Roman amphitheaters of the imperial age and the metamorphoses that occurred to the Chinese urban fabrics, originally made by courtyard houses, in the contemporary city), it is possible to extend to urban form the idea of casual co-optation for new uses of organs and anatomical parts developed for other reasons. This kind of reflections opens up innovative considerations on the potential of transitional urban analysis and its repercussions on evolutive urban transformation processes.

HU is the Hypergeometrical Universe Theory (HU)[1-8], proposed in 2006, where the Universe is a Lightspeed Expanding Hyperspherical Hypersurface and Gravitation is an absolute-velocity-dependent, epoch-dependent force. Here we introduce the Big Pop Cosmogenesis and show our calculations associated with the Equation of State of the Universe. This article is the first in a series of articles[9-22] supporting the paradigm shift.

It is proposed to incorporate the concepts of brain microbiota and microbial consciousness in the Orchestrated Objective Reduction (Orch OR) theory of human consciousness with the goal of increasing its explanatory and predictive powers. If consciousness arises from quantum computations in cytoskeletal structures inside human neurons, there is no theoretical impediment at hypothesizing that it might also occur in the cytoskeletal structures of the microbes resident in the human brains. If the concept of the brain microbiota is integrated in a general Orch OR theory, its explanatory and predictive powers would be vastly increased.

Portfolio weights solely based on risk avoid estimation error from the sample mean, but they are still affected from the misspecification in the sample covariance matrix. To solve this problem, we shrink the covariance matrix towards the Identity, the Variance Identity, the Single-index model, the Common Covariance, the Constant Correlation and the Exponential Weighted Moving Average target matrices. By an extensive Monte Carlo simulation, we offer a comparative study of these target estimators, testing their ability in reproducing the true portfolio weights. We control for the dataset dimensionality and the shrinkage intensity in the Minimum Variance, Inverse Volatility, Equal-risk-contribution and Maximum Diversification portfolios. We find out that the Identity and Variance Identity have very good statistical properties, being well-conditioned also in high-dimensional dataset. In addition, the these two models are the best target towards to shrink: they minimise the misspecification in risk-based portfolio weights, generating estimates very close to the population values. Overall, shrinking the sample covariance matrix helps reducing weights misspecification, especially in the Minimum Variance and the Maximum Diversification portfolios. The Inverse Volatility and the Equal-Risk-Contribution portfolios are less sensitive to covariance misspecification, hence they benefit less from shrinkage.

Manufacturing organizations shall recognize sustainability as a business occasion to capitalize on, rather than an undesirable pressing situation. Still, empirical evidence shows that this opportunity is hard to capture and communicate in global strategic decisions, through planning by tactical management, to daily operational activities. This paper systematically reviews the modeling challenges at the crossroad of value and sustainability decisions making, spotlighting methods and tools proposed in literature to link sustainability to customer value creation at strategic, tactical and operational level. While statistical results show that the topic of sustainability and value modeling is trending in literature, findings from content analysis reveal that recent attempts to promote a value-based view in the sustainability discussion remain at a strategic level, with most of the proposed indicators being suited for managerial decision-making. The lack of support at operational level points to the opportunity of cross-pollinating sustainability research with value-centered methodologies originating from the aerospace sector. The Value Driven Design framework is proposed as main hub from which to derive models supporting engineers and technology developers in the identification of win-win-win situations, where sustainable improvements are aligned with business advantages.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p