Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

南海西北部沉积物捕获器中颗石藻通量和属种组成变化记录

本文利用沉积物捕获器回收的连续时间序列沉降颗粒物样品,研究了南海西北部海南岸外陆坡外缘海域颗石藻的通量和属种组成变化及其环境意义。研究发现,东亚夏季风引起的海南岸外上升流以及冬季风导致的混合层深度增加都会刺激该区域颗石藻的生长,其中夏季上升流的影响尤为显著。从颗石粒属种组成来看,Florisphaera profunda是南海西北部中深层(1 000m)水体中主要的颗石粒优势种,此外Emiliania huxleyi,Gephyrocapsa oceanica和Gephyrocaps ericsonii等属种含量也颇高。然而在将颗石粒折算成颗石球数量后,Emiliania huxleyi则成为主要优势种。沉积物捕获器中F.profunda的相对百分含量与颗石粒总通量呈显著的负相关,表明F.profunda的相对含量与总的颗石藻生产力有着密切联系。本结果对于利用沉积物中的颗石藻记录,尤其是F.profunda相对含量变化,恢复和重建古海洋环境尤其是古海洋生产力的研究提供了直接的理论证据。

晚第四纪热带西太平洋Noelaerhabdaceae科颗石长度和质量变化及其影响因素

选取热带西太平洋暖池北部边缘西菲律宾海本哈姆高原(Benham Rise)MD06-3050站位的柱状样沉积物样品,利用双向圆偏光法拍摄并合成图像,通过SYRACO人工智能软件自动识别并测量和计算Noelaerhabdaceae科颗石的平均长度和平均质量。研究结果显示,自35万年以来,Noelaerhabdaceae科平均颗石长度和质量的变化趋势具有较强的相似性,两者的冰期/间冰期变化特征均不明显。根据颗石长度和质量计算得到的颗石钙化作用指标曲线与前两者的变化趋势也存在一定的相似性,说明研究海区颗石的平均质量和长度均可作为指示颗石藻钙化作用程度的指标。通过与冰芯记录的大气pCO_(2)变化曲线进行对比,发现在大气pCO_(2)浓度较高的冰期终止期以及间冰期早期,该科颗石的钙化作用相对较低,表明pCO_(2)在一定程度上影响了颗石藻的钙化作用。此外,对颗石的平均长度和质量进行23 ka周期滤波,两滤波曲线的变化与北纬15°夏季平均日照辐射曲线的变化较为一致,指示了地球天文轨道参数对颗石藻演化的调控作用。

Complete Modeling for Systems of a Marine Diesel Engine

This paper presents a simulator model of a marine diesel engine based on physical, semi-physical, mathematical and thermodynamic equations, which allows fast predictive simulations The whole engine system is divided into several functional blocks： cooling, lubrication, air, injection, combustion and emissions. The sub-models and dynamic characteristics of individual blocks are established according to engine working principles equations and experimental data collected from a marine diesel engine test bench for SIMB Company under the reference 6M26SRP1. The overall engine system dynamics is expressed as a set of simultaneous algebraic and differential equations using sub-blocks and S-Functions of Matlab/Simulink. The simulation of this model, implemented on Matlab/Simulink has been validated and can be used to obtain engine performance, pressure, temperature, efficiency, heat release, crank angle, fuel rate, emissions at different sub-blocks. The simulator will be used, in future work, to study the engine performance in faulty conditions, and can be used to assist marine engineers in fault diagnosis and estimation （FDI） as well as designers to predict the behavior of the cooling system, lubrication system, injection system, combustion, emissions, in order to optimize the dimensions of different components. This program is a platform for fault simulator, to investigate the impact on sub-blocks engine＇s output of changing values for faults parameters such as： faulty fuel injector, leaky cylinder, worn fuel pump, broken piston rings, a dirty turbocharger, dirty air filter, dirty air cooler, air leakage, water leakage, oil leakage and contamination, fouling of heat exchanger, pumps wear, failure of injectors （and many others）.

Ductal adenocarcinoma of the pancreatic head:A focus on current diagnostic and surgical concepts

Complete surgical resection still remains the only possibility of curing pancreatic cancer,however,only 10% of patients undergo curative surgery.Pancreatic resection currently remains the only method of curing patients,and has a 5-year overall survival rate between 7%-34% compared to a median survival of 3-11 mo for unresected cancer.Pancreatic surgery is a technically demanding procedure requiring highly standardized surgical techniques.Nevertheless,even in experienced hands,perioperative morbidity rates(delayed gastric emptying,pancreatic fistula etc.) are as high as 50%.Different strategies to reduce postoperative morbidity,such as different techniques of gastroenteric reconstruction(pancreatico-jejunostomy vs pancreatico-gastrostomy),intraoperative placement of a pancreatic main duct stent or temporary sealing of the main pancreatic duct with fibrin glue have not led to a significant improvement in clinical outcome.The perioperative application of somatostatin or its analogues may decrease the incidence of pancreatic fistulas in cases with soft pancreatic tissue and a small main pancreatic duct(< 3 mm).The positive effects of external pancreatic main duct drainage and antecolic gastrointestinal reconstruction have been observed to decrease the rate of pancreatic fistulas and delayed gastric emptying,respectively.Currently,the concept of extended radical lymphadenectomy has been found to be associated with higher perioperative morbidity,but without any positive impact on overall survival.However,there is growing evidence that portal vein resections can be performed with acceptable low perioperative morbidity and mortality but does not achieve a cure.

Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation

Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X-rays and computed tomographic(CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-toend anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions.

Biocompatibility of marine magnetotactic ovoid strain MO-1 for in vivo application

Magnetotactic bacteria are capable of biosynthesizing magnetic nanoparticles,also called magnetosomes,and swimming along magnetic field lines.The abilities endow the whole cells of magnetotactic bacteria with such applications as targeted therapy and manipulation of microrobots.We have shown that the intact marine magnetotactic bacteria MO-1 kill efficiently antibiotic-resistant pathogen Staphylococcus aureus in vivo,but the biocompatibility of this marine bacterium is unknown.In this study,the strain MO-1 was chosen to analyze its biocompatibility and potential for biomedicine applications.Results showed that MO-1 cells could be guided at 37℃ under an external magnetic field and swim in the blood plasma and urine.They could keep active locomotivity within 40 min in the plasma and urine,although their velocity slowed down.When incubated with human cells,magnetotactic bacteria MO-1 had no obvious effects on cellular viability at low dose,while the cell toxicity increased with the augmentation of the quantity of the MO-1 cells added.In the in-vivo experiments,the median lethal dose of magnetotactic bacteria MO-1 in rats was determined to be 7.9×10^(10) bacteria/kg.These results provided the foundation for the biocompatibility and safety evaluations of magnetotactic bacteria MO-1 and suggested that they could be basically used in clinical targeted therapy.

Adding body load modifies the vibratory sensation of the foot sole and affects the postural control

Background: Heavy backpacks are often used by soldiers and firefighters. Weight carrying could reduce the speed and efficiency in task completion by altering the foot sole sensitivity and postural control.Methods: In fifteen healthy subjects, we measured the changes in sensitivity to vibrations applied to the foot sole when standing upright or walking after load carrying(30% body weight). The participants were asked to judge different vibration amplitudes applied on the 2 nd or 5 th metatarsal head and the heel at two frequencies(25 and 150 Hz) to determine the vibration threshold and the global perceptual representation(Ψ)of the vibration amplitude(Φ)given by the Stevens power function(Ψ=k×Φ~n). Any increase in negative k value indicated a reduction in sensitivity to the lowest loads. Pedobarographic measurements, with computation of the center of pressure(COP) and its deviations, were performed during weight carrying.Results: The 25-Hz vibration threshold significantly increased after weight carrying when standing upright or walking.After standing with the added loads, the absolute negative k value increased for the 25 Hz frequency. After walking with the added loads, the k coefficient increased for the two vibration frequencies. Weight carrying significantly increased both the CoP surface and CoP lateral deviation.Conclusions: Our data show that weight carrying reduces the sensory pathways from the foot sole and accentuates the center of pressure deviations.

Multi-axial unsplit frequency-shifted perfectly matched layer for displacement-based anisotropic wave simulation in infinite domain

Multi-axial perfectly matched layer(M-PML),known to have lost the perfect-matching property owing to multi-axial coordinate stretching,has been numerically validated to be long-time stable and it is thus used extensively in linear anisotropic wave simulation and in isotropic cases where the PML becomes unstable.We are concerned with the construction of the M-PML for anisotropic wave simulation based on a second order wave equation implemented with the displacement-based numerical method.We address the benefit of the incorrect chain rule,which is implicitly adopted in the previous derivation of the M-PML.We show that using the frequency-shifted stretching function improves the absorbing efficiency of the M-PML for near-grazing incident waves.Then,through multi-axial complex-coordinate stretching the second order anisotropic wave equation in a weak form,we derive a time-domain multi-axial unsplit frequency-shifted PML(M-UFSPML)using the frequency-shifted stretching function and the incorrect chain rule.A new approach is provided to reduce the number of memory variables needed for computing convolution terms in the M-UFSPML.The obtained M-UFSPML is well suited for implementation with a finite element or the spectral element method.By providing several typical examples,we numerically verify the accuracy and long-time stability of the implementation of our M-UFSPML by utilizing the Legendre spectral element method.

Morphological and phylogenetic diversity of magnetotactic bacteria and multicellular magnetotactic prokaryotes from a mangrove ecosystem in the Sanya River,South China

Magnetotactic bacteria(MTB)are morphologically and phylogenetically diverse prokaryotes commonly able to produce magnetic nanocrystals within intracellular membrane-bound organelles(i.e.,magnetosomes)and to swim along geomagnetic field lines.We studied the diversity of MTB in the samples collected from a mangrove area in the Sanya River,Hainan,South China,using microscopic and microbial phylogenetic methods.Results of microanalysis and observation in microscopy and energy dispersive X-ray spectroscopy(EDXS)reveal a highly morphological diversity of MTB including unicellular cocci,vibrios,rod-shaped bacteria,and three morphotypes of multicellular magnetotactic prokaryotes(MMPs).In addition,analysis of the 16S rRNA gene showed that these MTB were clustered into 16 operational taxonomic units affi liated to the Alpha-,Delta-,and Gamma-proteobacteria classes within the Proteobacteria phylum.Meanwhile,by using the coupled fluorescence and transmission electron microscopy analysis,rodshaped bacteria,vibrio,and cocci were phylogenetically and structurally identified at the single-cell level.This study demonstrated highly diverse MTB communities in the mangrove ecosystem and provide a new insight into the overall diversity of MTB.

How light affect the magnetotactic behavior and reproduction of ellipsoidal multicellular magnetoglobules?

Magnetotactic bacteria(MTB)synthesize intracellular magnetic organelles,magnetosomes,which consist of magnetic crystals that are enveloped in a membrane.Magnetosomes are organized into a chain(s)and confer on cells a magnetic dipolar moment.This magnetic property allows MTB cells to align and swim along geomagnetic field lines,a movement referred to as magnetotaxis.Some MTB species change their swim direction in response to illumination by UV,violet and blue light.Here we analyzed the polarity of morphology,magnetism,and motion in Mediterranean multicellular magnetotactic prokaryotes,also called,magnetoglobules or MMP.The magnetoglobules were assembled from 60-80 cells into an asymmetric ellipsoidal morphology with a relative narrow and large end.They swam dominantly northward,parallel to the direction of the magnetic field,with the narrow-end as the leading side.In response to a reversal in the direction of the magnetic field,they aligned quickly along the magnetic field lines and kept swimming northward.Interestingly,under constant illumination,385-nm UV light,magnetoglobules changed their swimming direction southward anti-parallel to the direction of the magnetic field,with the large-end as the leading side.The change from a northward to southward direction occurred along with an increase of swimming speed.A minimum of 35-mW/cm^(2) irradiance of UV light was sufficient to trigger the swimming re-orientation.UV radiation also triggered the unidirectional division of magnetoglobules.Together these results revealed a coordination of the polarity of magnetoglobule morphology,magnetic moment,and swimming orientation,in response to magnetic and optical stimuli.The UV triggered the reversal of magnetotaxis and magnetoglobule division indicating the ecological significance of light for multicellular magnetotactic prokaryotes.

Hydro-geochemistry of groundwater and surface water in Dschang town(West Cameroon):Alkali and alkaline-earth elements ascertain lithological and anthropogenic constraints

The study aims to identify a suitable site for open and bore well in a farmhouseusing ground magnetic survey in south India.It also aims to define depth to granitoid and structural elements which traverse the selected area.Magnetic data(n=84)measured,processed and interpreted as qualitative and quantitatively.The results of total magnetic intensities indicate that the area is composed of linear magnetic lows trending NE-SW direction and circular to semi-circular causative bodies.The magnetic values ranged from-137 nT to 2345 nT with a mean of 465 nT.Reduction to equator shows significant shifting of causative bodies in the southern and northern directions.Analytical signal map shows exact boundary of granitic bodies.Cosine directional filter has brought out structural element trending NE-SW direction.Results of individual profile brought to light structurally weak zone between 90 m and 100 m in all the profile lines.Sudden decrease of magnetic values from 2042 nT to 126 nT noticed in profile line 6 between 20 m and 30 m indicates fault occurrence.Magnetic breaks obtained from these maps were visualized,interpreted and identified two suitable sites for open and bore well.Radially averaged power spectrum estimates depth of shallow and deep sources in 5 m and 50 m,respectively.Euler method has also been applied to estimate depth of granitoid and structural elements using structural indexes 0,1,2,and 3 and found depth ranges from<10 m to>90 m.Study indicates magnetic method is one of the geophysical methods suitable for groundwater exploration and site selection for open and borewells.

Resazurin as an indicator of reducing capacity for analyzing the physiologic status of deep-sea bacterium Photobacterium phosphoreum ANT-2200

Resazurin(RZ)is a weakly fl uorescent blue dye and can be reduced irreversibly to highly fl uorescent pink resorufi n(RF)that is reduced reversibly to colorless dihydroresorufi n(hRF)by photodeoxygenation,chemical reaction and reductive organic compounds produced through cell metabolism.Because of the reliable and sensitive fl uorescence-color change and noninvasive features,RZ has been used widely as a redox indicator in cell viability/proliferation assays for bacteria,yeast,and mammalian cells.However,RZ is used rarely for physiological characterization of marine microorganisms.Here,we developed a custom-made irradiation and absorption-analysis device to assess the reducing capacity and physiologic status of marine bacterial cultures.We measured the absorption spectra of RZ,RF,and hRF in the presence of the reducing compound Na 2 S and under visible-light irradiation.After establishing appropriate parameters,we monitored the color changes of RZ and its reduced derivatives to evaluate the coherence between reducing capacity,bioluminescence and growth of the deep-sea bacterium Photobacterium phosphoreum strain ANT-2200 under various conditions.Emission of bioluminescence is an oxidation process dependent upon cellular reducing capacity.Growth and bioluminescence of ANT-2200 cell cultures were impeded progressively with increasing concentrations of RZ,which suggested competition for reducing molecules between RZ at high concentration with reductive metabolism.Therefore,caution should be applied upon direct addition of RZ to growth media to monitor redox reactions in cell cultures.Analyses of the instantaneous reduction velocity of RZ in ANT-2200 cell cultures showed a detrimental eff ect of high hydrostatic pressure and high coherence between the reducing capacity and bioluminescence of cultures.These data clearly demonstrate the potential of using RZ to characterize the microbial metabolism and physiology of marine bacteria.

Morphology and Genetic Studies of Cymodocea Seagrass Genus in Tunisian Coasts

Specimens of Cymodocea(Viridiplantae,Magnoliophyta)collected on the Tunisian coasts showed a particular morphological and anatomical difference with the classical descriptions of Cymodocea nodosa(Ucria)Asch.the only species of this genus reported in the Mediterranean Sea.In order to precise the taxonomic identity of the new specimens we aimed in this work(i)to verify the identity of the new forms,(ii)to evaluate the genetic diversity of the population,(iii)to test the validity of the existing identification keys of the Tunisian Cymodocea populations.Four stations located in two regions of the Tunisian coasts were sampled.Leaf morphological and anatomical characters used in taxonomic identification were measured(e.g.,number of cross veins,shape of the apex).The genetic study was performed using three most common chloroplast markers for plant characterization(DNA barcodes rbcL,matK and trnHpsbA).The morphological study revealed the presence of three C.nodosa morphotypes,described here for the first time,while the molecular characterization did not allow the discrimination of these morphological types.In regard to these results,it would be wise to review the classical identification keys of the Cymodocea genus.

Determining osmotic suction through electrical conductivity for unsaturated low-plasticity soils

Determining osmotic suction from the electrical conductivity(EC)of soil pore water was widely reported in the literature.However,while dealing with unsaturated soils,they do not have enough soil pore water to be extracted for a reliable measurement of EC.In this paper,the chilled-mirror dew-point hygrometer and contact filter paper method were used to determine the total and matric suctions for low-plasticity soils with different salinities(0.05‰,2.1‰,and 6.76‰).A new piecewise function was proposed to calculate the osmotic suction,with the piecewise point corresponding to the first occurrence of precipitated salt in mixed salt solutions(synthetic seawater).EC,ion and salt concentrations used for osmotic suction calculation were transformed from the established relationships of mixed salt solution instead of experimental measurement.The calculated osmotic suction by the proposed equation and the equations in the literature was compared with the indirectly measured one(the difference between the measured total and matric suctions).Results showed that the calculated osmotic suction,especially the one calculated using the proposed function,was in fair agreement with the indirectly measured data(especially for specimens with higher salinity of 6.76‰),suggesting that the transformation of EC and concentrations from the established relationship is a good alternative to direct measurement for lowplasticity soil.In particular,the proposed method could be applied to unsaturated low-plasticity soils which do not have enough soil pore water for a proper EC measurement.

Dieback intensity but not functional and taxonomic diversity indices predict forest productivity in different management conditions: Evidence from a semi-arid oak forest ecosystem

The relationships between different aspects of diversity(taxonomic,structural and functional)and the aboveground biomass(AGB)as a major component of global carbon balance have been studied extensively but rarely under the simultaneous influence of forest dieback and management.In this study,we investigate the relationships between taxonomic,functional and structural diversity of woody species(trees and shrubs)and AGB along a gradient of dieback intensity(low,moderate,high and no dieback as control)under two contrasted management conditions(protection by central government vs.traditional management by natives)in a semi-arid oak(Quereus brantii Lindl.)forest ecosystem.AGB was estimated and taxonomic diversity,community weighted average(CWM)and functional divergence indices were produced.We found that the aerial biomass was significantly higher in the intensively used area(14.57(±1.60)t/hm^(2))than in the protected area(8.70(±1.05)t/hm^(2))due to persistence of some large trees but with decreasing values along the dieback intensity gradient in both areas.CWM of height(H),leaf nitrogen content(LNC)and leaf dry matter content(LDMC)were also higher in the traditional managed area than in the protected area.In contrast,in the protected area,the woody species diversity was higher and the inter-specific competition was more intense,explaining a reduced H,biomass and LDMC.Contrary to the results of CWM,none of the functional diversity traits(FDvar)was affected by dieback intensity and only FDvar values of LNC,leaf phosphorus content(LPC)and LDMC were influenced by management.We also found significantly positive linear relationships of AGB with CWM and FDvar indices in the protected area,and with taxonomic and structural diversity indices in the traditional managed area.These results emphasize that along a dieback intensity gradient,the leaf functional traits are efficient predictors in estimating the AGB in protected forests,while taxonomic and structural indices provide better results in forests under a high human pressure.Finally,species identity of the dominant species(i.e.,Brant’s oak)proves to be the main driver of AGB,supporting the selection effect hypothesis.

Quantitative Analysis of Lavender (<i>Lavandula angustifolia</i>) Essential Oil Using Multiblock Data from Infrared Spectroscopy

Near-infrared and mid-infrared spectroscopies were currently used to analyze natural compounds. During the last ten years various multiblocks methods were developed such as Concatenated PLS, Hierarchical-PLS (H-PLS), and MultiBlock-PLS (MB-PLS). These three algorithms were used to analyze 55 lavender (Lavandula angustifolia) essential oil samples. The results obtained were compared to the ones obtained respectively in NIR and MIR ranges. The accuracies of the models depend on the spectroscopic technique, pretreatment and the PLS methods. The results showed that the choice of the factor numbers used to build the multiblock models was the most important parameter for the H-PLS and MB-PLS methods.

Emergence of Toscana virus in the mediterranean area

Toscana virus(TOSV) is an arthropod-borne virus, identified in 1971, from Phlebotomus perniciosus and Phlebotomus perfiliewi in central Italy. TOSV belongs to the Phlebovirus genus within the Bunyaviridae family. As other bunyaviruses, the genome of TOSV consists of 3 segments(S for small, M for Medium, and L for Large) respectively encoding non structural and capsid proteins, envelope structural proteins, and the viral RNA-dependant RNA-polymerase. It is transmitted by sand flies. Therefore its distribution is dictated by that of the arthropod vectors, and virus circulation peaks during summertime when sandfly populations are active. Here, we reviewed the epidemiology of TOSV in the old world. First evidence of its pathogenicity for humans, specifically its propensity to cause central nervous system(CNS) infections such as meningitis and encephalitis, was reported in central Italy. After 2000, it was recognized that TOSV had a much larger geographic distribution than initially believed, and was present in most of the Western European countries located on the northern border of the Mediterranean Sea(Portugal, Spain, France, Greece, Croatia) as well as eastern countries such as Cyprus and Turkey. In the countries where TOSV is present, it is among the three most prevalent viruses in meningitis during the warm seasons, together with enteroviruses and herpesviruses. Up to now, epidemiological data concerning Northern Africa and other countries located south of the Mediterranean are scarce. TOSV must be considered an emerging pathogen. Despite the important role played by TOSV in CNS infections, it remains a neglected agent and is rarely considered by physicians in diagnostic algorithms of CNS infections and febrile illness during the warm season, probably because of the lack of information.

Predictive Factors of Intracranial Response of Immune Checkpoint Inhibitors in Patients with Brain Metastasis from Non-Small Cell Lung Cancer

Background: Immune checkpoint inhibitors (ICI)s were recently approved for the treatment of advanced non-small cell lung cancer (NSCLC). Whereas brain metastases (BM) are frequent in NSCLC patients, data are missing regarding ICIs intracranial efficacy and tolerance in patients with BM from NSCLC. Methods: This retrospective study was performed in the Multidisciplinary Oncology and Therapeutic Innovation department, Marseille, France between April 2013 and February 2016. Data from patients with NSCLC with at least one BM, and treated with ICIs (anti-PD1, anti-PDL1 or anti-CTL4) were analyzed. Clinical, biological data and outcomes were retrieved from electronic patients’ records. We assessed ICIs intracranial efficacy and tolerance. Results: Data from 55 patients were analyzed. Objective Response Rate (ORR) and Disease Control Rate (DCR) were respectively of 1.8 and 36.4%. Median overall survival was 17.2 months and median progression free survival was 2.9 months. Intracranial ORR (icORR) and intracranial DCR (icDCR) were respectively 16.4% and 45.5%. Both were independent of smoking status, intracranial treatment, performance status, pathology, molecular profile and the presence or number of BM at diagnosis. However, there was a trend towards an association between icORR and ECOG PS (p = 0.05), tobacco status (p = 0.057) and intracranial treatment. Adverse events were seen in 38.2% patients without identified predictive factor. Neurological symptoms appeared in 5.5% patients during immunotherapy and improved in 3.63% patients. Conclusions: ICIs can be used safely on patients with BM from NSCLC. However, intracranial response is heterogeneous in such patients and we showed ECOG PS, tobacco smoking and intracranial treatment to be associated with an improved icORR. This is the first study looking for predictive factors of intracranial response of ICIs in patients with BM from NSCLC.

Comparison of Efficacy and Safety of Artemisinin-Based Combination Therapies for Treating Uncomplicated Falciparum Malaria in Sub-Saharan African Countries: An Update on the Changes in Efficacy Using Network Meta-Analysis

Background: Several artemisinin-based combination therapies (ACT) are available to treat uncomplicated malaria in Africa. The present study aimed to assess the ranking of their efficacy and tolerance. Methods: A database of randomized controlled trials was retrieved from published papers. Network meta-analysis was used to compare efficacy on day 28 and day 42 after initiation of treatment. Age covariate effect on treatment outcome was assessed, and a modeling approach to reduce heterogeneity among trials was evaluated under the hypothesis of consistency in a meta-regression. Safety and adverse events were compared among different ACTs. A Bayesian analysis was performed to implement the consistency models using WinBUGS software. The results were compared to those of the frequentist approach using the R software. Results: Eighty-one articles, in which a total of 15 different ACTs were tested in more than 36,000 patients, were included. On day 28, dihydroartemisinin-piperaquine (DHPP) was more effective than artemether-lumefantrine (AL) before (odds ratio [OR], 1.83;95% confidence interval [CI], 1.31 - 2.56) and after age-covariate adjustment (OR, 1.70;95% CI, 1.20 - 2.43). The result was similar on day 42. DHPP occupied the top rank. The risk of having cough, diarrhoea or headache post-treatment was significantly lower with DHPP than AL. Artesunate-mefloquine (ASMQ) was associated with a significantly lower prevalence of vomiting or nausea (OR, 0.80;95% CI, 0.48 - 1.30) and headache (OR, 0.53;95% CI, 0.40 - 0.68) compared to AL. On the contrary, vomiting and nausea occurred more frequently after fixed-dose artesunate-amodiaquine formulation (ASAQf) than with AL (OR, 1.45;95% CI, 1.18 - 1.78). The risk of anaemia was higher with ASAQf and co-blistered artesunate-amodiaquine (ASAQc) than with AL. There was no significant difference in risk of anaemia (P > 0.05) between AL and different formulations of ASAQ. Conclusions: Based on the available evidence, this study demonstrated the superiority of DHPP, followed by AL, among currently recommended ACTs in terms of efficacy and tolerance. Network meta-analysis could be an alternative analytical tool but needs more data input from therapeutic efficacy studies. The determination of the best available therapy requires data triangulation and data science.