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ObjectiveProviding the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.MethodsAn integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).ResultsThe primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (≥ VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the ≥ VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04).ConclusionThese results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658).

The Rif Cordillera, an Alpine orogen in the Western Mediterranean, was developed by the interaction of Eurasian and African (Nubia) plates. Neotectonic deformations of the Rif foreland influence the relief, especially in post-nappe basins and their boundaries with Jurassic and Cretaceous carbonate mountain massifs, and they contribute to highlighting the recent evolution of the Cordillera. The topographic and hydrological lineaments of these basins were characterised on the basis of multi-scale morphostructural data analysis, supported by digital mapping and GIS. They were correlated with geological structures, essentially with fractures. The outcrops of the Upper Tortonian and Messinian deposits depict well-defined geometric shapes with roughly rectilinear boundaries, as defined by their contacts with the massive and rigid rocks of the Jurassic and Cretaceous series. Upper Tortonian deposits evidence major regional N70°E and N40°E lineaments, which are obliquely intersected by late structures. Messinian N120°E and N25°E lineaments, associated with N140°E lineaments, are also recognised. The interpretation of these lineaments as faults indicates the activity of two systems of transtensive sinistral and then dextral brittle shearing that correspond to two episodes of neotectonic deformation that played a decisive role in shaping the reliefs of the Eastern Rif. These deformations are particularly relevant to isolate basins and likely have a key role during the closure of the South Rifian corridor during the Mediterranean Messinian Salinity crisis.

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.

Welding is widely used in the aerospace, naval and automotive industries. Since high temperatures are involved in this process, solid state metallurgical changes are expected. These metallurgical changes can induce deformations and residual stresses in welded parts. The objective of this work is to develop a finite element calculation code, under the MATLAB environment, to predict the evolution of the various metallurgical transformations during TIG welding of C50 steel plates. In the proposed calculation procedure, we used Leblond’s equation and Waeckel’s model to characterize the metallurgical transformations during respectively heating and cooling stage. We also taken into account the effect of austenitic grain size on metallurgical transformations evolution. Thermal properties are introduced according temperature and phase proportions present during welding operation. Simulation results show that the metallurgical structure in the heat affected zone (HAZ) is largely related to welding thermal power and the plate preheating temperature. We compared simulation results to experimental measurements and the efficiency of the developed computational code was confirmed.

Under the additional assumption that the errors are normally distributed, the Ordinary Least Squares (OLS) method is the maximum likelihood estimator. In this paper, we propose, for a simple regression, an estimation method alternative to the OLS method based on a so-called Gaussian membership function, one that checks the validity of the verbal explanation suggested by the observer. The fuzzy estimation approach demonstrated here is based on a suitable framework for a natural behavior observed in nature. An application based on a group of MENA countries in 2015 is presented to estimate the employment poverty relationship.

Constructed wetlands (CWs) have been widely recognised for efficiently removing many pollutants from wastewater, making them vital for environmental bioremediation. The substrates used in constructed wetlands are crucial in determining their overall performance, notably their ability to improve nitrogen and phosphorus removal from wastewater. This study aims to investigate the possibility of removing pollutants from wastewater using a pilot scale vertical flow constructed wetland (VFCW) planted with Phragmites australis applied to various substrates, such as gravel and sand in an arid climate in Southeast Algeria. The study involved using four basins, filled with sand and gravel. Two were planted with Phragmites australis and the others were left as a control without vegetation. The efficiency of the filtration systems was evaluated based on various physicochemical and organic parameters. Results showed that the highest hydraulic retention time is in the 7 days. The removal efficiency values are 84.38% for biological oxygen demand (DBO5), 77.45% for chemical oxygen demand (COD), and 83.30% for total solid matter (TSS) in the planted gravel filter. The planted sand filter had even higher removal efficiency values, with 89.59%, 85.80%, and 86.63% for DBO5, COD, and TSS, respectively. Nitrate concentration increased in all filters due to the complete transformation of ammonium into nitrate. NO2 -, NH4 +, and PO4 3-removal efficiencies were also higher in the planted sand filter 74.45%, 95.43%, and 77.64%, respectively. [ABSTRACT FROM AUTHOR]

The polypyrrole@ZrO2–ZnO (PPy@ZrO2–ZnO) electrodes were synthesized using an in situ chemical oxidative method. The samples were characterized by XRD, FTIR, XPS, UV-vis, TGA, and BET. In addition, the electrochemical characteristics of the electrodes are tested by cyclic voltammetry (CV), galvanostatic charge and discharge (G.C.D.), and electrochemical impedance spectroscopy (E.I.S.). The values of the specific capacitances and the energy densities of PPy@ZrO2–ZnO (1.0) and PPy@ZrO2–ZnO (0.5) at a current density of 0.5 A g−1 are recorded as (395.3 F g−1 and 508.5 Wh·kg−1) and (195.3 F g−1 and 351.5 Wh·kg−1), respectively. Furthermore, the electrode stability for the formed samples was also determined, which exhibited specific capacitance retention at 90.2% for PPy@ZrO2–ZnO (1.0) and 82.4% for PPy@ZrO2–ZnO (0.5) after cycling up to 4,000 cycles. This work provides an efficient approach to the potential of the synthesized samples for application as electrodes in a supercapacitor.

This review summarizes the most relevant scientific literature related to the use of insects as alternative protein sources in poultry diets. The black soldier fly, the housefly, the beetle, mealworms, silkworms, earthworms, crickets, and grasshoppers are in the spotlight because they have been identified as an important future source of sustainable animal proteins for poultry feeding. Insect meals meet poultry requirements in terms of nutritional value, essential amino acid composition, nutrient digestibility, and feed acceptance. Furthermore, they are enriched with antimicrobial peptides and bioactive molecules that can improve global health. Results from poultry studies suggest equivalent or enhanced growth performances and quality of end-products as compared to fish meal and soybean meal. To outline this body of knowledge, this article states established threads of research about the nutrient profiles and the digestibility of insect meals, their subsequent effects on the growth and laying performances of poultry as well as the quality of meat, carcass, and eggs. To fully exploit insect-derived products, the effects of insect bioactive molecules (antimicrobial peptides, fatty acids, and polysaccharides) were addressed. Furthermore, as edible insects are likely to take a meaningful position in the feed and food chain, the safety of their derived products needs to be ensured. Some insights into the current knowledge on the prevalence of pathogens and contaminants in edible insects were highlighted. Finally, the effect of insect farming and processing treatment on the nutritive value of insect larvae was discussed. Our overview reveals that using insects can potentially solve problems related to reliance on other food sources, without altering the growth performances and the quality of meat and eggs.

تعتبر وكالة أناد من بين أولى هيئات دعم السلطات الوطنية لقطاع المؤسسات الصغيرة والمتوسطة حيث مكنت العديد من الشباب من انشاء مشاريع استثمارية مدرة للمداخيل ومستحدثة لمناصب الشغل، غير أن لوكالة مؤخرا أعلنت عن نسب ضخمة لتعثر مؤسساتها، مما استوجب طرح التساؤل حول أسباب هذا التعثر ومعرفة خطة الوكالة في مساعدة المؤسسات المتعثرة. اعتمدنا في دراستنا على المنهج الوصفي لتحليلي، القائم على وصف الظاهرة وتحليل احصائيات عمل الوكالة خلال سنة 0202 ، والتي عكست جهود الوكالة في محاولة للحفاظ على المؤسسات المستحدثة. ANADE agency is considered among the first bodies to support the SME sector, as it enabled many young people to create investment micro-projects, however, lately the agency announced huge percentages of institutional stumble. Our study aims to discover the phenomenon causes and the strategy of ANAD agency to help the stumbling institutions by analyzing the statistics of the agency work during the year 2021, which reflects its efforts to preserve the new institutions created.

Dopamine agonists are the first-line treatment of prolactinomas. The risk of developing de novo psychiatric symptoms during dopamine agonist therapy is low. Herein, we report the case of a 42-year-old woman with a giant prolactinoma who developed a psychiatric disorder after 1 day of cabergoline therapy initiation. She presented with amenorrhea, galactorrhea, headaches, and disturbed vision. Biological investigations revealed hyperprolactinemia (2975 ng/ml) with gonadotropin deficiency. Pituitary MRI showed a giant pituitary adenoma. The patient was treated with cabergoline at the dose of 1 mg twice weekly. One day after the treatment initiation, she developed acute delirium with temporospatial disorientation and compulsive medication use. These symptoms disappeared 1 week after the reduction of the dose of cabergoline. Patients with hyperprolactinemia receiving an initial high dose of cabergoline may develop changes in mood and behavior regardless of prior psychiatric history.

Abstract In the past decade, nucleic acid‐based drugs have emerged as an extremely promising approach for silencing specific disease‐related genes and targeting undruggable ones. However, most nucleic acid drug therapies have not advanced to clinical practice due to their poor stability against serum enzyme degradation and cytotoxicity. Nanoscale drug delivery vehicles show potential to improve efficacy of nucleic acid drugs via targeted delivery to disease‐causing genes, yet, safe and efficient nanocarriers remain elusive. Lipid‐based nanoparticles such as liposomes (LSs) and extracellular vesicles (EVs) are among the most extensively exploited nanoscale vehicles for therapeutic cargo delivery. LS‐based nucleic acid therapies have been used for several years, with many already adopted to the clinic. More recently, EVs hold considerable promise as nucleic acid delivery vehicles due to their high biocompatibility, low immunogenicity, and the inherent abilities to interact with target cells and cross biological barriers. Moreover, a novel LS/EV hybrid gene delivery system has been engineered to preserve the benefits of both systems and generate an advanced drug delivery system. The current review focuses specifically on LS‐ and EV‐based gene therapies and provides the key advantages and shortcomings of these systems with particular emphasis on their potential use as therapeutic vectors.

Abstract The causal protein of amyloid light‐chain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (κ) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzyme‐linked immunosorbent assay (ELISA) (Sebia) with N‐Latex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 non‐AL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA free‐light chain difference (dFLC) were lower than N‐Latex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the κ/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal κ/λ ratio by at least one assay. Only two patients had normal κ/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than N‐Latex but may be an alternative to nephelometry/turbidimetry in certain difficult cases.

The purpose of this work is to use the mixed fractional Brownian motion with parameter H ∈ ( 0 , 1 2 ) {H\in(0,\frac{1}{2})} as a modeling tool in financial mathematic, specifically in stochastic volatility modeling. We employ high frequency data from Oxford-Man Institute of Quantitative Finance Realized Library to estimate the smoothness of log-volatility. We show through empirical experiments that the measured smoothness of log-volatility is similar to that of mixed fractional Brownian motion when 0.09 ≤ H ≤ 0.2 {0.09\leq H\leq 0.2} . We propose to model the log-volatility by a mixed Fractional Brownian motion with H < 1 2 {H<\frac{1}{2}} and we construct a stationary mixed fractional Ornstein–Uhlenbeck process d ⁢ X t = - λ ⁢ ( X t - μ ) ⁢ d ⁢ t + γ ⁢ d ⁢ M t H , t ∈ [ 0 , T ] {dX_{t}=-\lambda(X_{t}-\mu)dt+\gamma dM_{t}^{H},t\in[0,T]} as a stationary model of log-volatility X t {X_{t}} and we show that it tends in distribution to the mixed fractional Brownian motion when λ → 0 {\lambda\rightarrow 0} . [ABSTRACT FROM AUTHOR]

This paper explores the role of digital culture in reducing digital violence on social media. Employing a descriptive-analytical approach within communication sociology, the study examines how digital culture can mitigate online violence. Findings indicate that social media is a fertile ground for various forms of digital violence. Thus, it is crucial to regulate and rationalize social media use through digital literacy, particularly provided by societal institutions starting with the family. The society plays a vital role in imparting the necessary principles, values, and skills for digital culture, thereby curbing violent behaviors in virtual spaces. [ABSTRACT FROM AUTHOR]

Background and Purpose: The pharmacology of flavonoids on β‐cell function is largely undefined especially in the context of defective secretion of insulin. We sought to identify flavonoids that increased the insulin‐secreting function of β‐cells and to explore the underlying mechanisms. Experimental Approach: INS‐1 β‐cells in culture and islets of Langerhans isolated from control and diabetic male rats were used for insulin secretion experiments. Pharmacological and electrophysiological approaches were used for mechanistic studies. Key Results: Among a set of flavonoids, exposure of INS‐1 β‐cells to resokaempferol (ResoK) enhanced glucose‐stimulated insulin secretion and therefore we further characterised its activity and its pharmacological mechanism. ResoK glucose‐dependently enhanced insulin secretion in INS‐1 β‐cells and pancreatic islets isolated from rats. Mechanistically, whole cell patch clamp recordings in INS‐1 cells showed that ResoK rapidly and dose‐dependently enhanced the L‐type Ca2+ current whereas it was inactive towards T‐type Ca2+ current. Accordingly, pharmacological inhibition of L‐type Ca2+ current but not T‐type Ca2+ current blocked the effects of ResoK on glucose‐stimulated insulin secretion. ResoK was still active on dysfunctional β‐cells as it ameliorated glucose‐stimulated insulin secretion in glucotoxicity‐induced dysfunctional INS‐1 cells and in pancreatic islets isolated from diabetic rats. Conclusion and Implications: ResoK is a glucose‐dependent activator of insulin secretion. Our results indicated that the effects of ResoK on insulin secretion involved its capacity to stimulate L‐type Ca2+ currents in cultured β‐cells. As ResoK was also effective on dysfunctional β‐cells, our work provides a new approach to stimulating insulin secretion, using compounds based on the structure of ResoK. [ABSTRACT FROM AUTHOR]