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Abstract Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining single particle tracking (SPT) and fluorescence correlation spectroscopy (FCS) techniques, to take advantage of their different sensitivities in order to analyze together slow and fast molecular movements. Thanks to calibrated samples, we developed a benchmark for quantitative analysis of molecular dynamics, to eliminate the main potential instrumental biases. We applied this workflow to study the diffusion of RPB1, the catalytic subunit of RNAP II. By a cross-analysis of FCS and SPT, we could highlight different RPB1 motility states and identifyed a stationary state, a slow diffusion state, and two different modes of subdiffusion. Interestingly, our analysis also unveiled the oversampling by RPB1 of nuclear subdomains. Based on these data, we propose a novel model of spatio-temporal transcription regulation. Altogether, our results highlight the importance of combining microscopy approaches at different time scales to get a full insight into the real complexity of molecular kinetics in cells.

Background: Aphasia affects approximately one-third of stroke patients and yet its rehabilitation outcomes are often unsatisfactory. More effective strategies are needed to promote recovery. Objective: We aimed to examine the efficacy and safety of the theta-burst stimulation (TBS) on the language area in the superior frontal gyrus (SFG) localized by personalized functional imaging, in facilitating post-stroke aphasia recovery. Methods: This randomized sham-controlled trial uses a parallel design (intermittent TBS [iTBS] in ipsilesional hemisphere vs. continuous TBS [cTBS] in contralesional hemisphere vs. sham group). Participants had aphasia symptoms resulting from their first stroke in the left hemisphere at least one month prior. Participants received three-week speech-language therapy coupled with either active or sham stimulation applied to the left or right SFG. The primary outcome was the change in Western Aphasia Battery-Revised (WAB-R) aphasia quotient after the three-week treatment. The secondary outcome was WAB-R aphasia quotient improvement after one week of treatment. Results: Ninety-seven patients were screened between January 2021 and January 2022, 45 of whom were randomized and 44 received intervention (15 in each active group, 14 in sham). Both iTBS (estimated difference = 14.75, p

Abstract Background Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurodegeneration and premature death. While miglustat can stabilize neurological manifestations in later onset forms of NP-C, its efficacy in the early-infantile neurological form has not been demonstrated. In this observational retrospective study, we compared long-term neurodevelopmental outcome and survival between an untreated and a treated group of early infantile NP-C patients. Methods Data available on all NP-C patients with early infantile neurological onset diagnosed in France between 1990 and 2013 were compiled. Patients with incomplete data or who had died from a systemic perinatal, rapidly fatal form were excluded. Results Ten patients were included in the treated group (year of birth: 2006–2012), and 16 patients in the untreated group [born 1987–2005 (n = 15), 2012 (n = 1)]. The median age at neurological onset was 9 months (5–18) in the treated group, and 12 months (3–18) in the untreated group (p = 0.22). Miglustat therapy was started at a median age of 24.5 months (9–29) and median duration was 30 months (11–56). Gastrointestinal adverse events were reported in 7/10 patients on miglustat. All patients developed loss of psychomotor acquisitions or additional neurological symptoms despite miglustat therapy. The ages of developmental milestones and neurological involvement did not significantly differ between the two groups. Four patients in the untreated group were lost to follow up. The 22 remaining patients had died by the end of the study and no patient survived beyond the age of 7.4 years. The median survival age was 4.42 years in the untreated group and 5.56 years in the treated group; the Kaplan–Meier survival curves were not significantly different (log-rank test: p = 0.11). Conclusions Miglustat allowed no significant long-term neurodevelopmental improvement nor significant increase of survival in patients with early infantile NP-C.

Abstract Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients’ tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.

Asthma and obesity are inflammatory diseases that have a considerable impact on the development of oral diseases. The purpose of this study was to establish the link between asthma induced inflammation, obesity and their impact on the development of periodontal disease. This is a cross-sectional study concerning 130 Algerians aged between 18 and 86 years old. 70 of the subjects were atopic asthmatics and 60 were control cases. The functional assessment of asthma was performed by spirometry. The CRP, ESR and eosinophil count confirmed the inflammation state. Our study revealed that women are more likely to develop asthma than men (p-value = 0.01). Snacking plays a key role in weight gain, where it is confirmed and statistically proven by a highly significant difference (p-value = 0.004). Treatment and more especially inhaled corticosteroids have a direct effect on obesity (p-value = 0.047) and on the aggravation of the quality of oral cavity. This study confirms also the high correlation between the control of asthma, the ESR ​​ and the CRP in obese asthmatic (p-value = 0.013, r = 0.225 and p-value = 0,255, r = 0.740 respectively), as well we observed a very high correlation between eosinophil level in the control of asthma in obese (p-value = 0,001, r =0.142) compared to leans ones. This study has highlighted and strengthened the link between asthma and obesity and their effect on oral health.

Merging Density Functional Theory (DFT) with the Quantitative Structure-Activity Relationship (2D/3D-QSAR) modeling represents a promising avenue for exploring antibacterial activity and discovering potential drugs effective against both gram-positive and gram-negative microorganisms. In this study, we employed this integrated approach to investigate a newly synthesized and promising class of 1,3,4-oxadiazole derivatives renowned for their high performance as antibacterial agents. To ensure an accurate characterization and thorough description of the targeted biological activity, we systematically evaluated various DFT functionals to precisely predict the geometrical and electronic descriptors of the investigated compounds. These descriptors were crucial for developing and validating the proposed 2D/3D-QSAR models. Our results reveal that the introduction of a donor group enhances the antibacterial activity of the derivatives. The analysis of molecular descriptors underscores the positive impact of this modification on the compounds' efficacy against bacteria. Additionally, our experimental compounds exhibit favorable characteristics concerning oral bioavailability, a crucial aspect in drug development. The identification of robust correlations between antibacterial activity and specific descriptors was achieved by conducting an extensive analysis that encompassed multiple linear regression (MLR), Random Forest (RF), and Artificial Neural Networks (ANN). Subsequently, a partial least squares (PLS) model was employed to construct 3D-QSAR models based on the Comparative Molecular Field Analysis (CoMFA) and Comparative Similarity Indices Analysis (CoMSIA) descriptors. Validation of the output models was performed using leave-one-out and bootstrapping strategies. The resultant 2D/3D-QSAR models demonstrated a high correlation between experimental and predicted activity values. Leveraging these models, the developed MLR model, expressed as pMIC = -12.704 + 0.260 logP – 6.104 10-03 SAG – 51.385 qN33, serves as a valuable tool for predicting antibacterial activity. we indicate that the machine learning methods, Artificial Neural Networks (ANN) and Random Forest (RF), outperform traditional models in accurately predicting antibacterial activity. We designed ten novel molecules, subjecting them to molecular docking and molecular dynamics simulations to predict their optimal postures when docked in the target and gain insights into the formed interactions. Additionally, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis was applied to discern the potential behavior of these novel compounds in the human body. As a result, the newly suggested chemical, X4, X10, exhibited robust inhibitory potential against gram-negative microbes.

Background: Type 2 diabetes is a major public health problem responsible for several macro and microvascular complications, including diabetic nephropathy. The main objective of this study was to describe the epidemiological profile of type 2 diabetic patients at admission to a reference center for chronic diseases and to explore associated factors with a glomerular filtration rate decline (GFR). Methods: This retrospective cohort study aims to examine the epidemiological characteristics of patients with type 2 diabetes who had at least one consultation between November 2005 and December 2020. Results: The study included 19,953 patients, of whom 67.8 % were women, with an average age of 58.2 ± 12.2 years. The majority (64.7 %) had a diabetes duration of less than 5 years. On admission, 37.6 % of patients had high blood pressure, 41.8 % were overweight, while 31.5 % were obese. Nearly 9 % of patients had at least one complication on admission: 2.6 % had heart disease, 2 % had nephropathy, 1.8 % had retinopathy, 0.7 % had neuropathy and 0.5 % had a diabetic foot. The study found that 76.8 % of patients had poorly controlled diabetes, and 30.1 % had a GFR 〈 60 ml/min/1.73 m². Women, patients over 65 years, those with a diabetes duration 〉 30 months, hypertensive patients, those with at least one complication on admission, patients with overweight or obesity, and those with positive albuminuria had significantly lower GFR (p

Lactoferrin is an iron-binding glycoprotein with antibacterial, antitumor, and immunomodulatory functions derived from milk and mucosal secretions. Lactoferrin is used in various products, such as infant formula milk powder, nutritional supplements, and cosmetics. Researchers have developed new technologies to produce lactoferrin because there are limitations in the separation and purification of lactoferrin from milk that cannot compensate for the market demand. Therefore, synthetic systems of lactoferrin have been developed with the development of genetic engineering, and the structure of lactoferrin expressed in heterologous systems is very similar to that of natural lactoferrin. The structure and functions of lactoferrin and the design and construction of synthetic lactoferrin biological systems, especially microbial synthetic systems, including prokaryotic and eukaryotic host-expression systems, are described. On the basis of these results, we summarize the challenges and solutions for constructing systems of high-yield lactoferrin. The development directions of recombinant lactoferrin are discussed in this review. Overall, the design and development of these synthetic biological systems have allowed us to explore the great potential of the industrial large-scale preparation of lactoferrin.

Climate change mitigation necessitates increased investment in green sectors. This study proposes a methodology to predict green finance growth across various countries, aiming to encourage such investments. Our approach leverages time-series Conditional Generative Adversarial Networks (CT-GANs) for data augmentation and Nonlinear Autoregressive Neural Networks (NARNNs) for prediction. The green finance growth predicting model was applied to datasets collected from forty countries across five continents. The Augmented Dickey-Fuller (ADF) test confirmed the non-stationary nature of the data, supporting the use of Nonlinear Autoregressive Neural Networks (NARNNs). CT-GANs were then employed to augment the data for improved prediction accuracy. Results demonstrate the effectiveness of the proposed model. NARNNs trained with CT-GAN augmented data achieved superior performance across all regions, with R-squared (R2) values of 98.8%, 96.6%, and 99% for Europe, Asia, and other countries respectively. While the RMSE for Europe, Asia, and other countries are 1.26e+2, 2.16e+2, and 1.16e+2 respectively. Compared to a baseline NARNN model without augmentation, CT-GAN augmentation significantly improved both R2 and RMSE. The R2 values for the Europe, Asia, and other countries models are 96%, 73%, and 97.2%, respectively. The RMSE values for the Europe, Asia, and various countries models are 2.24e+2, 7e+2, and 2.07e+2, respectively. The Nonlinear Autoregressive Exogenous Neural Network (NARX-NN) exhibited significantly lower performance across Europe, Asia, and other countries with R2 values of 74%, 52%, and 86%, and RMSE values of 1.11e+2, 3.63e+2, and 1.8e+2, respectively.

Introduction: Brucellosis is an important zoonosis problem worldwide. It’s also recognized as a clinical and health problem in Algeria. Methods: This research is a descriptive study to determine the prevalence of brucellosis and some clinical and epidemiological aspects of hospitalized patients in the agro-pastoral region of Theniet El Had for ten years, between March 2013 and March 2023. During the study period, 180 patients (61.66% men and 38.33% women) with confirmed brucellosis based on clinical symptoms and serological tests were hospitalized for treatment. Patients working with animals were requested to screen their animals (383 goats from 27 suspicious farms with no history of vaccination), 16, 71% of goats from 44%, and 44% herds were infected. Results: The occurrence of human cases varied from 49.18 to 66.02pcm (cases/100,000 inhabitants) with an average of 58, 48pcm (cases/100,000 inhabitants). Almost half of hospitalized people who had been in contact with animals could have been contaminated by direct contact. Consumption of unpasteurized dairy products during the last 2 months was at the order of 95.55%. A family history of Brucellosis was observed in 36 (20%) patients. Brucella epididymo-orchitis occurred in 18.01% while relapse occurred in a small proportion of 7.22%. Conclusions: Local authorities should prevent human brucellosis with surveillance systems, disease declarations, biosecurity programs, and warning communities about the hazards of consumption of unpasteurized milk and dairy products.

Solid-liquid equilibria for binary mixtures of {Methyl palmitate (1) + Naphthalene (2)} were measured using differential scanning calorimeter (DSC). Simple eutectic behaviours for this system are observed. The experimental results were correlated by means of the NRTL, Wilson, UNIQUAC and ideal models. The root-mean-square deviations of the solubility temperatures for all measured data vary from 0.5477 K (for UNIQUAC model) to 3.34K; the deviation depend on the model used. The best solubility correlation was obtained with UNIQUAC model and this observation confirms previous results.

ObjectiveA meta-analysis of proton magnetic resonance spectroscopy studies to investigate alterations in brain metabolites in people with HIV (PWH), the relationship between metabolite alterations and combination antiretroviral therapy (cART), and the relationship between metabolite alterations and cognitive impairment.MethodsThe PubMed database was searched for studies published from 1997 to 2020. Twenty-seven studies were identified, which included 1255 PWH and 633 controls. Four metabolites (N-acetyl aspartate [NAA], myo-inositol [mI], choline [Cho], and glutamatergic metabolites [Glx]) from 5 brain regions (basal ganglia [BG], frontal gray and white matter [FGM and FWM], and parietal gray and white matter [PGM and PWM]) were pooled separately using random-effects meta-analysis.ResultsDuring early HIV infection, metabolite alterations were largely limited to the BG, including Cho elevation, a marker of inflammation. cART led to global mI and Cho normalization (i.e., less elevations), but improvement in NAA was negligible. In chronic PWH on cART, there were consistent NAA reductions across brain regions, along with Cho and mI elevations in the FWM and BG, and Glx elevations in the FWM. Cognitive impairment was associated with NAA reduction and to a lesser degree mI elevation.ConclusionsThe BG are the primary region affected during early infection. cART is successful in partially controlling neuroinflammation (global mI and Cho normalization). However, neuronal dysfunction (NAA reductions) and neuroinflammation (mI and Cho elevations) persist and contribute to cognitive impairment in chronic PWH. Novel compounds targeting NAA signal pathways, along with better neuroinflammation control, may help to reduce cognitive impairment in PWH.

This paper examines the existence of Okun’s law in Algeria over the period of 1970–2020 using both the gap and differences model.

Abstract High-intensity Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a recent, non-invasive line of treatment for medication-resistant tremor. We used MRgFUS to produce small lesions in the thalamic ventral intermediate nucleus (VIM), an important node in the cerebello-thalamo-cortical tremor network, in 13 patients with tremor-dominant Parkinson’s disease or essential tremor. Significant tremor alleviation in the target hand ensued (t(12) = 7.21, p

Background: Robot-assisted pyeloplasty is the most frequently performed robotic procedure in children. A retroperitoneal approach limits surgical trauma and avoids peritoneal irritation. This led to the establishment of the criteria for day surgery (DS) and a related clinical care pathway. Objective: To assess the feasibility and safety of DS in children undergoing retroperitoneal robot-assisted laparoscopic pyeloplasty (R-RALP). Design, setting, and participants: We performed a bicentric prospective study (NCT03274050) over 2 yr involving the two major paediatric urology teaching hospitals in Paris. A clinical pathway and a prospective research protocol were specifically established. Intervention: DS in selected children undergoing R-RALP. Outcome measurements and statistical analysis: The primary outcomes were DS failure, 30-d complications, and readmission rates. The secondary outcomes included preoperative characteristics, perioperative parameters, and surgical outcomes. Quantitative variables were expressed as medians with interquartile ranges. Results and limitations: Thirty-two children fulfilled specific inclusion criteria and were consecutively selected for DS following R-RALP. The median patient age was 7.6 yr (4.1–11.8) and weight 25 kg (14–45). The median console time was 137 min (108–167). There were no intraoperative complications or conversions. Six children were kept under observation overnight and discharged the following day due to persistent pain (n = 3), parental anxiety (n = 2), or a prolonged procedure (n = 1). The median duration of hospital stay of the 26 children in the DS setting was 12.7 h (12.2–13.2). During the 30-d period, there were four emergency room visits (15%) resulting in two patients requiring readmission (8%): one for febrile urinary tract infection (Clavien-Dindo II) and one child with no JJ stent for urinoma (Clavien-Dindo IIIb). Radiological studies confirmed improvement in dilatation for all cases with no recurrence (median follow-up: 15 mo). Conclusions: This prospective case series is the first to demonstrate the feasibility and safety of DS in children undergoing R-RALP, obviating the need for routine inpatient care. Excellent results can be achieved by careful patient selection, a clear clinical pathway, and a dedicated team. Further evaluation is warranted to assess the cost effectiveness. Patient summary: This study shows that day surgery after robotic pyeloplasty is both safe and effective in selected children.

Homologous recombination deficiency is linked with platinum-based chemotherapy response in triple-negative breast cancer (TNBC) but methods to clinically identify these patients are lacking. Here, using patient-derived xenografts of TNBC the authors demonstrate that shallow HRD is predictive of response to platinum-based chemotherapy.

Coordinated hunting is widely observed in animals, and sharing rewards is often considered a major incentive for this success. However, it is unclear what causal roles are played by this reward-sharing mechanism. In order to systematically examine the effects of sharing rewards in animal coordinated hunting, we conduct a suite of modeling experiments using a state-of-the-art multi-agent reinforcement learning algorithm. The models are trained and evaluated with a task that simulates real-world collective hunting. We manipulate four evolutionarily important variables: reward distribution, hunting party size, free-rider problems, and hunting difficulty. Our results indicate that individually rewarded predators outperform predators that share rewards, especially when the hunting is difficult, the group size is large, and the action cost is high. Moreover, predators with shared rewards suffer from the free-rider problem. We conclude that sharing reward is neither necessary nor sufficient for modeling animal coordinated hunting through reinforcement learning.

This work aims to present the solvency system currently in the insurance sector in Algeria, more precisely the Solvency I Directive. To identify the shortcomings and limitations of the prudential regulation and finally, to offer recommendations necessary to ensure the development of the activity of insurance in Algeria, and consequently the economy in general. Thus, to present the transition from the Solvency I prudential standard to the Solvency II prudential standard, which was implemented on the insurance market in Europe on January 01, 2016. Finally, the Algerian regulation cannot stay away from international reforms, including the Solvency II standard; it must adapt his system to comply with these standards.

ABSTRACT Pathogenic Rickettsia species proliferate within the cytoplasm of permissive host cells in vivo. The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for Rickettsia growth. However, a dramatic host/pathogen interplay occurs when Rickettsia encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful Rickettsia parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of Rickettsia within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different Rickettsia species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens. IMPORTANCE Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

This paper aims to study the replacement of a Diesel Generator based plant by a hybrid renewable system. To overcome both source and load fluctuations, a battery-based storage system is used. The renewable energy resources available in southern Algeria is considerable. Actually, this region has one of the largest wind capacity in the country with wind speeds up to 4 to 6 m/sec, the wind energy density is 280-Watt/m2/ day. Meanwhile, the solar potential is characterized by an average duration of sunshine above 11 hours/day and the energy they can provide for a large-scale industry can change the development of the region and of the whole country. Genetic algorithms under optimtool is used to size hybrid systems. The resulting levelized cost of electricity (LPSP) of $0.262/kWh, is competitive and economical if a large-scale electricity production is undertaken. The loss of power supply probability or customer dissatisfaction rate (LPSP) of 1.2545 %, which is within standard limits.

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1) was discovered as an enzyme that detoxifies cyanide by conversion to thiocyanate (rhodanide) using thiosulfate as substrate; this rhodanese activity was subsequently identified to be almost exclusively located in mitochondria. More recently, the emphasis regarding its function has shifted to hydrogen sulfide metabolism, antioxidant defense, and mitochondrial function in the context of protective biological processes against oxidative distress. While TST has been described to play an important role in liver and colon, its function in the brain remains obscure. In the present study, we therefore sought to address its potential involvement in maintaining cerebral redox balance in a murine model of global TST deficiency (Tst−/− mice), primarily focusing on characterizing the biochemical phenotype of TST loss in relation to neuronal activity and sensitivity to oxidative stress under basal conditions. Here, we show that TST deficiency is associated with a perturbation of the reactive species interactome in the brain cortex secondary to altered ROS and RSS (specifically, polysulfide) generation as well as mitochondrial OXPHOS remodeling. These changes were accompanied by aberrant Nrf2-Keap1 expression and thiol-dependent antioxidant function. Upon challenging mice with the redox-active herbicide paraquat (25 mg/kg i.p. for 24 h), Tst−/− mice displayed a lower antioxidant capacity compared to wildtype controls (C57BL/6J mice). These results provide a first glimpse into the molecular and metabolic changes of TST deficiency in the brain and suggest that pathophysiological conditions associated with aberrant TST expression and/or activity renders neurons more susceptible to oxidative stress-related malfunction.

The type of symmetry exhibited by a travelling wave can have important implications for its behaviour and properties, such as its polarization, dispersion, and interactions with other waves or boundaries. The fractional differential Duffing problem refers to the mathematical modelling of nonlinear, damped oscillations of a system with fractional derivatives. It is a generalization of the classical Duffing equation, which describes the behaviour of a nonlinear, damped oscillator (the equation becomes symmetric under time-reversal). The fractional derivatives allow for a more accurate description of the system's memory and hereditary properties. The solution of the fractional Duffing equation can provide insight into the complex dynamic behaviour of various physical, biological, and engineering systems. We are concerned with studying a new differential Duffing fractional problem. It involves some sequential Caputo derivatives with an infinite series of Riemann–Liouville integrals and some other functions. We begin by proving a first existence and uniqueness result, then we discuss two types of stability for the obtained uniqueness result. An illustrative examples is given to show the applicability of the result. We are also concerned with applying the Tanh method to obtain new classes of travelling wave solutions for three important classes of (Khalil) fractional conformable problems; the generalized equation of Duffing, the Landau–Ginzburg–Higgs equation and the Sine–Gordon one. Some numerical simulations are plotted and a conclusion is given at the end.

ABSTRACTObjectives In this paper, we outline and compare pharmaceutical pricing and reimbursement policies for in-patent prescription medicines in three Maghreb countries, Algeria, Morocco, and Tunisia, and explore possible improvements in their pricing and reimbursement systems.Methods The evidence informing this study comes from both an extensive literature review and a primary data collection from experts in the three studied countries.Key findings Twenty-six local experts where interviewed Intervieweesincluded ministry officials, representatives of national regulatory authorities, health insurance organizations, pharmaceutical procurement departments and agencies, academics, private pharmaceutical-sector actors, and associations. Results show that External Reference Pricing (ERP) is the dominant pricing method for in-patent medicines in the studied countries. Value-based pricing through Health Technology Assessment (HTA) is a new concept, recently used in Tunisia to help the reimbursement decision of some in-patent medicines but not yet used in the pricing of innovative medicines in the studied countries. Reimbursement decision is mainly based on negotiations set on Internal Reference Pricing (IRP).Conclusion Whereas each country has its specific regulations, there are many similarities in the pricing and reimbursement policies of in-patent medicines in Algeria, Morocco, and Tunisia. The ERP was found to be the dominant method to inform pricing and reimbursement decisions of in-patent medicines. Countries in the region can focus on the development of explicit value assessment systems and minimize their dependence on ERP over the longer-term. In this context, HTA will rely on local assessment of the evidence.

The objective of this paper is to review the electrification modes associated with the Great Algerian South Networks (GSN). The study focuses on the conceptualization of the GSN through the dimensioning of mini-grids. Given the remoteness and difficulties of fuel supply, a series of reforms have been undertaken to promote the energy transition and ensure the development of these regions through the realization of hybrid systems in order to reduce the dependence on fossil fuel sources by ensuring energy savings.

In this article, we study the growth of meromorphic solutions of linear delay-differential equation of the form [\ \sum_{i=0}^{n}\sum_{j=0}^{m}A_{ij}(z)f^{(j)}(z+c_{i})=F(z),/] where Aij(z) (i = 0, 1, ..., n, j = 0, 1, ..., m, n, m ∈ N) and F(z) are meromorphic of finite logarithmic order, ci(i = 0, ..., n) are distinct non-zero complex constants. We extend those results obtained recently by Chen and Zheng, Bellaama and Belaïdi to the logarithmic lower order.