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Background: Morocco faces a substantial public health challenge due to diabetes mellitus, affecting 12.4% of adults in 2023. The Moroccan population makes extensive use of phytotherapy and traditional medicine to address the difficulties this chronic condition poses. The aim of this study is to document the use of medicinal plants in traditional medicine for managing type 2 diabetes in the provinces of the Casablanca-Settat region. Methods: The study employed a semi-structured questionnaire for data collection. A study was conducted between August 1st and September 30th, 2023, and 244 individuals diagnosed with diabetes were invited to take part in the research, all of whom used at least one medicinal plant to manage type 2 diabetes, by visiting primary healthcare facilities in Morocco. The analysis included the use of Relative Frequency of Citation (RFC) to scrutinize the data. Results: A total of 47 plant species belonging to 25 families were documented. Notably, the Apiaceae, Lamiaceae, and Fabaceae families were frequently mentioned in the context of treating type 2 diabetes in Morocco. Prominent among the cited plant species were Sesamum indicum L., Lepidium sativum L., followed by Foeniculum vulgare Mill., and Rosmarinus officinalis L. Seeds emerged as the plant part most commonly mentioned, with infusion being the prevailing preparation method and oral consumption being the most frequently depicted method of administration. Conclusion: This research underscores the practicality of incorporating traditional medicine into the healthcare framework of the Casablanca-Settat region. The findings not only offer valuable documentation but also have a vital function in safeguarding knowledge regarding the utilization of medicinal plants in this locality. Moreover, they provide opportunities to delve deeper into the phytochemical and pharmacological potential of these plants. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The present study aims to provide a global and regional estimate of the prevalence of COPD based on spirometry according to the two most widely used diagnostic criteria of COPD: fixed ratio (FR) and lower limit of normal (LLN). Methods: We conducted a systematic review of the literature according to PRISMA guidelines. MEDLINE, Web of Sciences, and Scopus databases were searched to identify studies on the spirometry-based prevalence of COPD in individuals aged 40 years and older. The meta-analysis was performed using MedCalc 19 software. Results: In total, 42 of the 3393 studies reviewed were eligible for inclusion. The overall prevalence of COPD in people aged 40 years and older was 12.64% (95% CI 10.75%-14.65%) and 7.38% (95% CI 5.47% − 9.55%) based on FR and LLN criteria, respectively. By gender, men had a higher prevalence of COPD compared to women (15.47%; 95% CI 12.22%-19.02% for men versus 8.79%; 95% CI 6.94%-10.82% for women). Using the LLN criteria, the prevalence of COPD in both sexes was almost identical (8.67%; 95% CI 8.44%- 8.90% for men and 8.00%; 95% CI 6.42% − 9.73% for women). We reported a high prevalence of COPD among smokers and the elderly by both definitions of airway obstruction. Regional prevalence estimates using the FR definition indicate that the highest COPD prevalence was recorded in the Americas and the lowest was recorded in the Eastern Mediterranean region. Using the LLN definition, the highest prevalence was recorded in the Southeast Asian region and the lowest prevalence was recorded in the American region. The most common COPD stage was stage II, with a prevalence of 50.46%. The results indicate a huge lack of prevalence data in the African and Eastern Mediterranean region. The results were given using a random-effect model due to the high heterogeneity between studies. Conclusion: Results show that the prevalence of COPD differs according to the diagnostic criteria used. In addition, management and prevention strategies targeting risk factors for COPD are certainly needed to reduce the global burden of this chronic respiratory disease. [ABSTRACT FROM AUTHOR]

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Summary: BRAF inhibitors are an effective treatment for BRAFV600E‐mutated, risk‐organ‐positive Langerhans cell histiocytosis (RO+ LCH). However, cell‐free BRAFV600E DNA often persists during therapy and recurrence frequently occurs after therapy discontinuation. To identify a pathological reservoir of BRAFV600E‐mutated cells, we studied peripheral blood cells obtained from six infants with RO+ multisystem (MS) LCH that received targeted therapy. After cell sorting, the BRAFV600E mutation was detected in monocytes (n = 5), B lymphocytes (n = 3), T lymphocytes (n = 2), and myeloid and plasmacytoid dendritic cells (n = 2 each). This biomarker may offer an interesting tool for monitoring the effectiveness of new therapeutic approaches for weaning children with RO+ LCH from targeted therapy. [ABSTRACT FROM AUTHOR]

Discrete search and rescue path planning for a moving target problem is computationally hard. Despite heuristic methods proposed so far, for which efficiency is further plagued by random episodic target kinematic behavior, qualifying real solution goodness and specifying optimality gap still remain elusive. In this paper a new alternate formulation is proposed to solve the search path planning problem for a moving target. Rather than tackling explicitly the original problem model, a remarkable property is exploited to solve a conjugate mixed-integer linear programming problem. The approach lies on a compact open-loop search path planning problem model with anticipated feedback to efficiently minimize probability of detection failure as opposed to traditionally maximize cumulative probability of success. Preserving path solution optimality, solving the conjugate problem proves very valuable in significantly reducing computational complexity. This is mainly achievable by virtue of the resulting problem objective property which concisely defines the function to be minimized in terms of terminal belief contributions only. For the first time optimal or upper bound solution computation are made possible in reasonable time for practical size problems. A network representation is further utilized to simplify modeling and facilitate constraint specification. Computational results show the strength of the approach for one and two searching agent problem instances. [ABSTRACT FROM AUTHOR]

Summary: The nucleoside analogue, 2‐chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long‐term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long‐term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow‐up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five‐year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five‐year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long‐term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory. [ABSTRACT FROM AUTHOR]

Background: Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed.Methods: Among 1482 children (< 15 years) registered in the French LCH registry (1994-2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure.Results: The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine-corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging.Conclusions: Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy. [ABSTRACT FROM AUTHOR]

Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late‐onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND‐LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND‐LCH. The 10‐year cumulative incidence of cND‐LCH was 4·1%. cND‐LCH typically affected patients previously treated for a multisystem, risk organ–negative LCH, represented in 69·4% of cND‐LCH cases. Pituitary gland, skin and base skull/orbit bone lesions were more frequent (P < 0·001) in cND‐LCH patients compared to those without cND‐LCH (respectively 86·1% vs. 12·2%, 75·0% vs. 34·2%, and 63·9% vs. 28·4%). The 'cND susceptible patients' (n = 671) i.e., children who had experienced LCH disease with pituitary or skull base or orbit bone involvement, had a 10‐year cND risk of 7·8% vs. 0% for patients who did not meet these criteria. Finally, BRAFV600E status added important information among these cND susceptible patients, with the 10‐year cND risk of 33·1% if a BRAFV600E mutation was present compared to 2·9% if it was absent (P = 0·002). [ABSTRACT FROM AUTHOR]

This paper presents a technique for integrating information about future customer requests to improve decision making for dynamic vehicle routing. We use a co-evolutionary approach to generate better waiting strategies such that the expected number of late-request customers who are served is maximized. An empirical evaluation of the proposed approach is performed within a previously reported hybrid genetic algorithm for the dynamic vehicle routing problem with time windows. Comparisons with other heuristic methods demonstrate the potential improvement that can be obtained through the application of the proposed approach. [ABSTRACT FROM AUTHOR]

The BRAF V600E mutation is reported in half of patients with Langerhans cell histiocytosis ( LCH). This study investigated the detection of the BRAF V600E allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAFV600E-mutated LCH were investigated to detect ccf BRAF V600E at diagnosis ( n = 48) and during follow-up ( n = 17) using a picolitre-droplet digital PCR assay. At diagnosis, ccf BRAFV600E was positive in 15/15 (100%) patients with risk-organ positive multisystem ( RO+ MS) LCH, 5/12 (42%) of patients with RO− MS LCH and 3/21 (14%) patients with single-system ( SS) LCH ( P < 0·001, Fisher's exact test). The positive BRAFV600E load was higher for RO+ patients (mean, 2·90%; range, 0·04-11·4%) than for RO− patients (mean, 0·16%; range, 0·01-0·39) ( P = 0·003, Mann-Whitney U test). After first-line vinblastine-steroid induction therapy, 7/7 (100%) of the non-responders remained positive for ccf BRAFV600E compared to 2/4 (50%) of the partial-responders and 0/4 of the complete responders ( P = 0·002, Fisher's exact test). Six children treated with vemurafenib showed a clinical response that was associated with a decrease in the ccf BRAFV600E load at day 15. Thus, ccf BRAFV600E is a promising biomarker for monitoring the response to therapy for children with RO+ MS LCH or RO− LCH resistant to first-line chemotherapy. [ABSTRACT FROM AUTHOR]

As discrete multi-agent static open-loop target search path planning known to be computationally hard recently proved to be solvable in practice in the homogeneous case, its heterogeneous problem counterpart still remains very difficult. The heterogeneous problem introduces broken symmetry reflected by dissimilar sensing ability/capacity, agent capability and relative velocity and, is further exacerbated when operating under near real-time problem-solving constraints, as key decision variables grow exponentially in the number of agents. Departing from the homogeneous agent model already published, new integer linear and quadratic programming formulations are proposed to reduce computational complexity and near-optimally solve the discrete static search path planning problem involving heterogeneous agents. The novelty consists in taking advantage of typical optimal path solution property to derive new tractable problem models. At the expense of a slightly accrued computational complexity, the proposed quadratic integer program formulation conveys considerable benefit by keeping key decision variables linear in the number of agents. The convexity property of its defined objective function further allows ensuring global optimality when a local optimum is computed. Special agent network representations capturing individual agent decision moves are also devised to simplify problem modeling and expedite constraint modeling specification. As a result, cost-effective quadratic program implementation for realistic problems may be achieved to rapidly compute near-optimal solutions, while providing a robust bound on solution quality through Lagrangian relaxation. [ABSTRACT FROM AUTHOR]

The French national cohort of children with Langerhans cell histiocytosis ( LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ ( RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96·6% (95% confidence interval: 95·4-97·5%) overall, improving from 92% pre-1998 to 99% post-1998 ( P < 0·001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent. [ABSTRACT FROM AUTHOR]

Threshold Accepting, a variant of Simulated, Annealing, is applied for the first time to a set of 356 benchmark instances for the Vehicle Routing with Time Windows. The Threshold Accepting metaheuristic is used to improve upon results obtained with a recent parallel genetic algorithm and a multi-start local search to illustrate its value as a post-processor. The Threshold Accepting metaheuristic is shown to be a fast and versatile post-processor that can be imposed upon a variety of heuristic or metaheuristic approaches for vehicle routing to get better results in both theoretical and practical application. [ABSTRACT FROM AUTHOR]

A route-directed hybrid genetic approach to address the Vehicle Routing Problem with Time Windows is presented. The proposed scheme relies on the concept of simultaneous evolution of two populations pursuing different objectives subject to partial constraint relaxation. The first population evolves individuals to minimize total traveled distance while the second focuses on minimizing temporal constraint violation to generate a feasible solution, both subject to a fixed number of tours. Genetic operators have been designed to incorporate key concepts emerging from recent promising techniques such as insertion heuristics and large neighborhood search to further explore the solution space. Results from a computational experiment over common benchmark problems show that the proposed technique matches or outperforms some of the best heuristic routing procedures, providing six new best-known solutions. In comparison, the method proved to be fast, cost-effective and highly competitive. [ABSTRACT FROM AUTHOR]

Background: Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions.Methods: A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response.Results: The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events.Conclusion: VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication. [ABSTRACT FROM AUTHOR]