For decades, Metal oxide (MOX) gas sensors have been commercially available and used in various applications such as the Smart City, gas monitoring, and safety due to advantages such as high sensitivity, a high detection range, fast reaction time, and cost-effectiveness. However, several factors affect the sensing ability of MOX gas sensors. This article presents the results of a study on the cross-sensitivity of MOX gas sensors toward ambient temperature and humidity. A gas sensor array consisting of temperature and humidity sensors and four different MOX gas sensors  was developed. The sensors were subjected to various relative gas concentrations, temperatures (from 16 °C to 30 °C), and humidity levels (from 75% to 45%), representing a typical indoor environment. The results proved that the gas sensor responses were significantly affected by the temperature and humidity. The increased temperature and humidity levels led to a decreased response for all sensors, except for MiCS-6814, which showed the opposite response. Hence, this work proposed regression models for each sensor, which can correct the gas sensor response drift caused by the ambient temperature and humidity variations. The models were validated, and the standard deviations of the corrected sensor response were found to be 1.66 kΩ, 13.17 kΩ, 29.67 kΩ, and 0.12 kΩ, respectively. These values are much smaller compared to the raw sensor response , indicating that the model provided a more stable output and minimised the drift. Overall, the results also proved that the models can be used for MOX gas sensors employed in the training process, as well as for other sets of gas sensors. Metal oxide (MOX) gas sensors have been used in many applications, such as monitoring indoor and outdoor air quality, due to their design simplicity, longer lifetime, high sensitivity, and lower price . StudiesThe fundamental principles of MOX gas sensors are based on redox reactions that take place on the surface of the sensitive layer. MOX sensors are highly affected by the temperature of the MOX layer. Conventional operation of conductometric MOX gas sensors takes place on the sensing layer at temperatures in the range of 200–500 °C ,10,11. TMoreover, MOX gas sensors suffer from high sensitivity to air humidity ,12. Gene2–SiO2) composite layer to enhance the temperature cross-sensitivity [Several studies have focused on removing or correcting the cross-sensitivity of MOX gas sensors to temperature and humidity. Cross-sensitivity results in response drift because of changes in the surface reaction of MOX gas sensors. Therefore, many researchers have extensively studied the cross-sensitivity of the sensor toward several factors and proposed an alternative to enhance its response. Wang discussed the cross-sensitivity that affects the MOX sensor response, including the chemical components, surface modification, microstructures of sensing layers, and ambient temperature and humidity . Chauhansitivity . Ghosh ositivity . Nair cositivity . Anothersitivity .Sensor response drift is one of the most challenging problem in gas sensor technology because the temporal shift of the sensor response is observed under the same working conditions. Such operating condition factors cause phenomena such as dust, speed, wind, and fluctuations of the ambient environmental variables  and system hardware ,19. Ther2 value for the multiple regression analysis was 0.874, which is higher than the value of R2 (0.801) obtained from the univariate regression analysis. This shows that the multiple regression analysis fits the data better.The regression method can be classified into univariate and multiple linear regression models. Univariate regression is a model that can be tested for only one independent variable. In contrast, the multiple regression model can describe the relationships between several independent variables and a response variable. Based on studies performed by Badura, raw data were fitted to univariate and multiple regression models . The R2 Moreover, in multiple regression analysis, more factors can be considered and form a complex model, such as temperature and humidity. This method has the potential to solve the cross-sensitivity problem. The findings of Sohn were used to create partial-least-squares calibration models . The effIn this study, we attempt to learn the relationship between the response of MOX gas sensors towards the ambient temperature and humidity. The novelty of the work is that we proposed new correction models for specific MOX sensors  to minimise the effect of ambient temperature and humidity on its response. Previous studies have failed to develop a model that includes both ambient temperature and humidity parameters in a single model. In addition, some studies are also concerned with the effect of the heater’s temperature rather than the ambient temperature. With this improvement, the gas sensors are expected to provide a more stable response, less affected by environmental conditions fluctuation.LV is the voltage across Generally, MOX gas sensors consist of metal oxide semiconductor layers that react to targeted gas based on the conductance principle. A simple electrical circuit can be developed to convert the change in conductivity to an output signal, indicating the gas concentration. A general electrical schematic diagram used to monitor the MOX sensor response is shown in In addition, the characteristics and response of the MOX sensor are highly affected by the temperature of the metal oxide layer. The temperature range of the layer is said to lie between 200 °C and 500 °C ,27,28 anA sensor array module was developed that consisted of sensor arrays and was covered by a partially closed chamber, as shown in In order to obtain different relative concentrations of VOC, six different ethanol solutions were prepared  by mixing an ethanol solution with certain volumes of distilled water. These solutions were labelled as c0, c50, c200, c500, c1000, and c2000 respectively, and bubbled with clean air in different experimental settings. Note that the actual concentration was not measured since the main objective is to study the variation of the sensor’s response with respect to varying temperatures and humidity at relatively different levels of gas concentrations. The incubator was set to cause the temperature to oscillate between 16 °C and 30 °C uniformly between the 30th and 630th min, while the humidity was gradually reduced from 75% to 45% and increased again to 75% within the same period. This setting was used to minimise the time effect. It is because, over the continuous bubbling process, the concentration of ethanol gas might decrease. The calculated average of the outcomes of both temperature controls (ramp up and ramp down) can generate a more reliable pattern. Finally, the incubator was set to ramp up the temperature to 20 °C and ramp down the humidity to 65%, leaving the incubator to meet these conditions for 15 min, and then it was left for 30 min. The gas sensor responses to these conditions during the last 30 min were used as reference data , while the period between the 30th and 630th min was used as training data. The whole experiment is repeated with all humidity levels and at different ethanol solution concentrations.F can predict the corrected response In this study, a gas sensor response model was created. Given The k-fold cross-validation (CV) approach was utilised to evaluate the performance and provide a measure of fit, i.e., mean square error (MSE), to select candidate models for the dataset. The dataset was randomly divided into k equally sized subsamples in this approach. At every sample time, k − 1 subsample was gathered to form the training dataset, and the other subsample was used as the validation dataset. The procedure was repeated k times so that every k subsample was in a test set only once. Then, the entire k-fold process was repeated n times, with new randomly drawn subsamples. Finally, the MSEs were obtained from all the n repetitions, the k-folds were averaged, and the standard deviation was calculated. The technique has an advantage over the conventional testing method  in that all samples are used for both training and testing. Therefore, more reliable results were obtained.In this section, the plots of the sensors’ responses acquired based on the experimental setup described in The overall patterns of the sensor responses with respect to varying temperature and humidity were analysed and used to predict the general form of the Equation used for modelling. The sensor responses decrease almost linearly with increasing temperature.The sensor responses decrease almost linearly with increasing humidity.Generally, based on the analysis of the 2D and 3D plots for each gas sensor response, two main observations can be made:SR values resulting from temperature and humidity variations are examined through a multiple linear regression model in the next section. The correction of gas response fluctuations was studied and is valid for the examined VOCs.Hence, the models proposed to correct SR, T, and H). In general, the MSE patterns for all sensors decreased as the complexity of the model increased . The MSEs for m1 and m2 for all sensors were significantly higher than for the other models because of the absence of important interaction terms . The averaged MSE dropped substantially from m2 to m3, suggesting that the terms T and H should be separated. The findings also indicate that the individual temperature and humidity terms are significant, as in m4. The change from C4RsTH in m4 to (4RSTC + 5RSHC) in m5 also improved the result.The linear regression method with 10-fold CV was utilised to show the effect of temperature and humidity fluctuations on the gas sensor response, and the correction was performed using supervised linear regression. First, the k-fold CV technique was utilised to measure the fit  of the candidate models. The averaged MSEs and standard deviations for all models see  when usiTH or STHR) in m6 and m7 on the sensor response has never been discussed in the literature. With this interaction term, a false correction may be produced.The results show similar average MSEs and standard deviations in m5, m6, and m7. Therefore, these can potentially be used as a model to solve this problem. However, m5 was chosen because of its lower complexity and avoiding overfitting due to additional interaction terms. In addition, the interaction between the temperature and humidity  that minimises the effects of temperature and humidity.Second, the models were independently generated based on the m5 basis function and utilised all gas sensors’ entire dataset. Third, the coefficients for model m5 were determined based on the supervised linear regression method explained in Finally, the reliability of the proposed models –(13)) was further verified by using different gas sensors instead of the ones used in the model generation experiments. To avoid confusion, these gas sensors were denoted as MiCS-5524V2, GM-402BV2, GM-502BV2, and MiCS-6814V2. The experiment was conducted in a closed room (closed door and window), and an air conditioner was used to control the temperature and humidity. The sensors were exposed directly to ambient air instead of being enclosed in the previously mentioned chamber. To observe the gas sensor response at different temperatures, the setting of the air conditioner was repeatedly changed between 30 °C and 16 °C for two cycles with an interval of 2 h between sets. However, the room’s actual temperature did not reach the set values (30 °C and 16 °C) because of the air conditioner efficiency and ambient conditions outside the room. Furthermore, the narrow openings of the windows and door result in some heat transfer and minor air exchange. In addition, the humidity throughout the experiments depended on the air conditioner’s setting. Changes in temperature and humidity were observed to affect all the gas sensor responses. As shown in the plots, the gas sensor responses were inversely proportional to the change in temperature and humidity, except for MiCS-6814. Therefore, the modelled gas sensor response could minimise the effects of temperature and humidity. However, the plots slowly deviated from the reference over time because of changes in air composition throughout the experiment. This was more pronounced when the air conditioner setting was changed, owing to significant air exchange, while the door was opened to change the setting. Based on the results, the general model was verified, and the cross-sensitivity affected by temperature and humidity was minimised for all sensors, even though different sensors were used. Moreover, the experiments revealed that the model was effective when the sensor was directly exposed to the ambient environment.3 gas. Therefore, linear regression was performed to produce different models: FMiCS5524, FGM402B, FGM502B, and FMiCS6814. The model works such that, given the sensor response (SR), temperature (T), and humidity (H), it can predict a corrected sensor response MOX gas sensors are widely used in gas-sensing technologies. However, this sensor type is cross-sensitive to the temperature and humidity of the ambient air. Therefore, an attempt was made to correct the MOX gas sensor response for a more reliable gas-sensing operation. The incubator was used to vary the ambient temperature and relative humidity while exposing the gas sensors to six different concentrations of ethanol gas. The results indicate that the response of the sensors decreases almost linearly as temperature and humidity increase, except for the MiCS-6814 sensor, which has the opposite behaviour because of its layer built to react with NH


Three-dimensional (3D) graphene was grown by the thermal CVD method on the nickel foam and subsequently coated with thin films of anatase employing the sol–gel method. Thereafter, it was gratifyingly demonstrated that the hybrid nanomaterial, TiO2/3D-GF-Ni, was able to bring about more than 90% decolorization of methyl orange dye after 30 min under simulated sunlight irradiance. Moreover, the efficiency of the methyl orange decolorization was 99.5% after three successive cycles. This high-performance photocatalyst which can effectively decolorize methyl orange will most likely make a great contribution to reducing environmental pollution by employing renewable solar energy.The development of highly efficient sunlight-driven photocatalysts has triggered increased attention due to their merit in effluent treatment through a chemically green approach. To this end, we present herein the synthesis and characterization of the TiO The development of efficient and cost-effective wastewater treatment materials capable of recycling and improving water quality is one of the main problems society is facing today. After agriculture, the textile industry, particularly fabric dyeing, is the second largest polluter of surface water. Representing more than half of the industrial colorants , highly Titanium dioxide is an extensively employed photocatalyst, but its wide band gap and high recombination rate render it with low efficiency and responsivity limited to the UV range. With the current burden to develop highly efficient sunlight-driven photocatalysts, heterojunctions that will allow both efficient separation of the photogenerated charge carriers and visible light absorption have been intensively explored. The physicochemical properties of graphene and its derivatives have triggered interest in employing them as a photocatalyst in a hybrid heterostructure ,5,6,7,8.These hybrid materials have shown photocatalytic activity under solar irradiation, but their industrial application is limited by inefficient regeneration and separation after the photochemical reaction. To overcome these limitations, nanocomposites with magnetic phases have been developed ,20,21,222 layer. The advantage of the sol–gel technique comes from its low-temperature synthesis in a reproducible manner, requiring a limited infrastructure and enabling industrial application with minimal costs. To adjust the hydrophobicity of the graphene’s surface and introduce oxygen-containing groups for efficient metal oxide–graphene interaction, the graphene surface underwent UV-ozone treatment before titania deposition. This method modifies the graphene’s surface energy while preserving good transport properties of graphene due to the negligible presence of defect density ..2 syntheOn the other hand, the results of the diffuse reflectance measurements estimating the band gap of anatase indicated an increase in the band gap with increasing calcination time and temperature. Thus, increasing the calcination time from 2 to 3 h, an evident increase, from 3.17 to 3.41 eV, was observed when the temperature was 450 °C, but only a slight increase, from 3.35 to 3.4 eV, when the temperature was 550 °C. These results are in accordance with the consensus that the absorption edge of anatase, associated with the indirect transition, is around 3.2 eV.2/3D-GF/Ni photocatalyst was selected to be completed at a calcination temperature of 450 °C for 2 h.Considering structural characterization which indicated only the presence of a well-defined anatase phase without significant changes in crystallinity with increasing the calcination temperature or time at 550 °C or 3 h, and the lowest band gap of 3.17 eV observed for the 450 °C and 2 h, the synthesis of the TiO2 sol and calcination at 450 °C for 2 h, the thin TiO2 film follows the architecture of the Ni foam , 195 (Eg), 398 (B1g), 517 (B1g or A1g), and 636 (Eg) cm−1, indicating the 100% anatase phase [−1. Additionally, the absence of the D band, commonly centered at ~1350 cm−1 and associated with the disorder and defects in the graphene layers, indicates the growth of high quality, defect-free graphene network that preserves its structure even after anatase formation. The other two characteristic vibration bands of graphene, G and 2D, related to the crystallinity and symmetry of the graphene, and the number of graphene layers, are centered at 1577 cm−1 and 2724 cm−1. However, the IG/I2D ratio, describing the number of layers in the 3D graphene network, is larger than unity indicating a multilayer structure of the synthesized graphene.The formation of the anatase phase is also confirmed in the Raman spectrum depicted in se phase ,30. Depi2/3D-GF/Ni hybrid was assessed by the photodegradation of the anionic dye, methyl orange, under both UV light and simulated sunlight. The dye solution was a Na2SO4-based medium to simulate the wastewater environment since Na2SO4 is a common promoter and buffering agent in the dyeing industry. All photocatalytic tests were carried out in a 10 mL dye solution of pH 3 to favor the anionic dye adsorption on the positively charged anatase surface. Initially, the photolysis of the methyl orange was evaluated by exposing the dye solution to both UV light and simulated sunlight in the absence of the photocatalyst. The constant concentration of the methyl orange working solution observed in the absence of the photocatalyst under both UV light and simulated sunlight indicates the high stability of the dye, as well as the inefficient degradation without an adsorbent or photocatalyst  were performed, the degradation efficiency was 62%, with an increase to 73% when four deposition cycles (1.6 mg TiO2) were completed. However, as noticed in 2 and four deposition cycles (8 mg TiO2), a near complete decolorization (99.2%) was observed after 180 min of UV irradiation, and around 98% after 150 min.In the presence of the TiO process b–d. The 2 specimen, as well as the increase to 38% for the specimen of 4 cm2  and three (6 mg TiO2) deposition cycles, with a degradation efficiency of 99.5% and 99.2%, respectively after 90 min of irradiation. The deficiency of TiO2 to absorb visible light is supported by the absence of photodegradation in the case of the TiO2 film deposited on the 2 × 2 cm2 glass substrate . Surface morphology and structure indicate the formation of an interconnected, porous, and robust graphene network in the shape of the nickel template and the TiO


Finally, saracatinib significantly decreased TGF-β gene expression. Our results indicate that treatment responsiveness varies between IPF patients in relation to their oxidative and inflammatory status. Interestingly, saracatinib tends to be more effective in IPF than standard antifibrotic drugs.Idiopathic pulmonary fibrosis (IPF) has a detrimental prognosis despite antifibrotic therapies to which individual responses vary. IPF pathology is associated with oxidative stress, inflammation and increased activation of SRC family kinases (SFK). This pilot study evaluates individual responses to pirfenidone, nintedanib and SFK inhibitor saracatinib, markers of redox homeostasis, fibrosis and inflammation, in IPF-derived human bronchial epithelial (HBE) cells. Differentiated HBE cells from patients with and without IPF were analyzed for potential alterations in redox and profibrotic genes and pro-inflammatory cytokine secretion. Additionally, the effects of pirfenidone, nintedanib and saracatinib on these markers were determined. HBE cells were differentiated into a bronchial epithelium containing ciliated epithelial, basal, goblet and club cells. NOX4 expression was increased in IPF-derived HBE cells but differed on an individual level. In patients with higher NOX4 expression, pirfenidone induced antioxidant gene expression. All drugs significantly decreased NOX4 expression. IL-6 ( Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease of unknown etiology, characterized by scarring of the lung tissue associated with a high burden of disease and a detrimental survival rate ,2 In addRecently, two clinically approved antifibrotic drugs, pirfenidone and nintedanib, were shown to ameliorate the course of the disease by slowing down its progression of , althoughttps://clinicaltrials.gov/ct2/show/NCT04598919), accessed on 11 November 2022.Recently, the non-receptor tyrosine inhibitor saracatinib , which inhibits SRC family kinases (SFK) and BCR-ABL kinases, has been suggested as a potential treatment strategy for IPF ,17,18. SIPF pathology is now commonly considered an epithelial-driven and fibroblast-activated process with mild inflammation , and effPatients were recruited at the Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg  supplemented with bovine pituitary extract (4 µL/mL), epidermal growth factor (10 ng/mL), insulin (5 µg/mL), hydrocortisone (0.5 µg/mL), triiodo-L-thyronine (6.7 ng/mL) and transferrin (10 µg/mL) , sodium selenite , ethanolamine , phosphorylethanolamine , sodium pyruvate , adenine , Hepes , 1x GlutaMAX (Gibco), and 10 µM Rock-inhibitor , as described previously [Human bronchial epithelial (HBE) cells were obtained from endobronchial lining fluid (ELF) of IPF patients and controls by minimally invasive bronchoscopic microsampling (BMS) during bronchoscopy from subsegmental airways as previously described  After BMeviously .After reaching confluency, cells were transferred to 12-well tissue culture inserts and plated at 90.000 cells/insert . After 2–3 days, cells were subjected to air–liquid interface (ALI) culture by removing the medium from the apical chamber and adding PneumaCult-ALI media  to the basal chamber only. Differentiation into a pseudostratified mucociliary epithelium was achieved after approximately 24–27 days. At day 28, cells were stimulated for 24 h with different concentrations of pirfenidone , nintedanib  or saracatinib   that were added to the basolateral side of the medium to mimic the systemic administration of these drugs to patients. After this incubation, RNA, proteins and supernatants were collected see .To validate differentiation to a pseudostratified mucociliary epithelium, ALI cultures were stained with specific antibodies. The cells were washed with PBS and fixed on slides with 4% paraformaldehyde for 20 min at 4 °C. Afterwards, mounted slides were rinsed with PBS and incubated in PBS containing 0.2% Triton X-100 for 2 min. Slides were then cut in 4 pieces and washed with PBS, blocked in PBS containing 1% bovine serum albumin (BSA) for 30 min, and stained with antibodies against keratin 5 , tubulin-β4 , CC10  and mucin 5AC  overnight at 4 °C. The next day, slides were washed with PBS and blocked for 10 min in PBS/1% BSA. Alexa Fluor secondary antibodies 488 and 594  were added, and slides were incubated for 45 min at 37 °C, followed by Hoechst staining  for 10 min at room temperature. Images were obtained with confocal microscopy (Leica TCS SP5) and Leica Application Suite X software.Secretion of interleukin (IL)-8 and IL-6 in cell culture supernatants was determined using human ELISA DuoSet kits  according to the manufacturer’s instructions.Cells were plated in a 96-well plate, grown to 70% confluency and afterwards stimulated for 24 h. The next day, MTT (Sigma-Aldrich) solution  was added to all wells and incubated for 1 h at 37 °C in the dark. Cells were washed with HBSS, and DMSO was added to solubilize the formed formazan. Afterwards, the plate was incubated for 30 min on a shaker, and absorbance was measured at λ = 540 nm.LDH cell death assay was used according to the instructions of the manufacturer .−∆∆Ct method to relatively quantify the expression of genes of interest. These genes included the ROS-producing enzyme NOX4 as well as selected antioxidant genes  according to the manufacturer’s instructions. The RNA concentration was determined using a NanoDrop spectrophotometer (Thermo Scientific), after which cDNA was synthesized from 500 ng isolated RNA using IScript  according to the manufacturer’s instructions. RT-PCR was performed using SYBR Green PCR Supermix (BioRad) with 4.4 μL of 50 times diluted cDNA and 0.5 μmol/L predesigned primers. PCR amplifications were carried out for up to 55 cycles of denaturation  and annealing/elongation  for selected genes . The gennt genes .p value less than 0.05.All quantitative data were represented as means ± SEM. Statistical differences between groups were evaluated by means of 1-ANOVA analysis corrected with Bonferroni’s post hoc analysis or by means of Student’s t-test in GraphPad Prism software  and considered significant at a Human bronchial epithelial (HBE) cells were isolated from the endobronchial lining fluid (ELF) of patients with IPF and non-IPF controls by BMS and grown in ALI cultures. After 28 days of ALI, a complete bronchial airway epithelium consisting of ciliated epithelial, goblet, club and basal cells has developed. The HBE cells were stained with specific antibodies and confocal microscopy was performed showing the successful differentiation of BMS-derived cultures  from conp = 0.19). Additionally, NOX4 mRNA expression was negatively correlated with the diffusing capacity for carbon monoxide (DLCO) (p = 0.19), as well as CAT (p = 0.23) and SOD2 (p = 0.21), appeared to be slightly downregulated in IPF patients, whereas HO-1 and SOD1 tended to be slightly upregulated  B, althouegulated C.To assess the effects of putative IPF drugs, cells were treated for 24 h at dose ranges similar to those used in previous studies ,17,33,34Next, we examined the effect of the selected concentrations of pirfenidone, nintedanib and saracatinib on mRNA expression of NOX4 and selected antioxidant genes. All drugs significantly reduced NOX4 expression in IPF patients A, but dip < 0.05, IPF development is associated with an increase in fibrotic gene expression, and therefore expression of collagen (COL1A1), fibronectin (FN) and TGF was analyzed. Interestingly, neither pirfenidone nor nintedanib affected COL1A1 A, FN FiB or TGF p = 0.02).As IPF pathology can be accompanied by low-grade chronic inflammation, secretion of pro-inflammatory interleukin (IL)-6 and IL-8 was determined using ELISA. HBE cells isolated from IPF patients did indeed secrete increased levels of IL-6 and IL-8 compared to HBE cells from non-IPF patients A,B. TreaIn this pilot study, we demonstrated that ELF-derived cells from patients with IPF and non-IPF controls can be successfully differentiated into a fully stratified bronchial epithelium, consisting of ciliated epithelial, basal, goblet and club cells. Although our previous study revealed differences in basal airway cell expression between patients with IPF compared to non-IPF controls , this diIPF is a complex heterogeneous disease, and although there are two drugs licensed, they are not fully effective in every patient, as disease progression still occurs during their therapeutic use . Given tOur pilot findings with respect to the effectiveness of saracatinib in IPF are in line with the recent study of Ahangari et al. in which this SFK inhibitor was shown to revert various fibrogenic pathways, including immune responses and extracellular matrix organization, in both animal and human models of pulmonary fibrosis . AdditioOur study is the first study that uses pulmonary bronchial epithelial cells obtained from newly diagnosed and untreated IPF patients to evaluate treatment effects on markers of antioxidant genes and pro-inflammatory cytokine release. Although the current consensus is that alveolar epithelial cells are the key cells driving IPF pathogenesis, there is emerging new evidence that bronchial basal cells are also involved in the development of pulmonary fibrosis. The recent PROFILE study has shown pronounced staining in fibrotic lesions throughout the metaplastic epithelium and enhanced serum levels of three serum proteins, i.e., surfactant protein D, CA19-9 and CA-125 . This fiOur research, being a pilot study, obviously has several limitations. First, the small sample size is likely to have contributed to our inability to detect other potentially biologically relevant differences, and extended studies with larger patient groups would be needed to fully address this. Second, our IPF patients also differed from our control subjects with respect to age and smoking history, which clearly could confound analysis of lung function and redox homeostasis and potentially influenced the results obtained. Additionally, it would be of interest to also measure ROS levels as well as reactive nitrogen species (RNS) levels in the cultures to directly assess the oxidant burden. Lastly, the working mechanisms of pirfenidone and nintedanib in epithelial cells remain to be elucidated to fully understand and clinically translate our findings. The fact that nintedanib also inhibits non-receptor tyrosine kinases including SFK  suggestsWhile designing personalized co-treatment strategies for pulmonary fibrosis, the optimal drug-delivery route should be taken into account. Currently, both pirfenidone and nintedanib are orally administered and associated with various unintended side effects. Direct targeted delivery to the lungs might not only reduce these side effects but might also result in higher local drug concentrations, thereby potentially increasing their efficacy . InteresIn conclusion, there are still many open questions regarding IPF treatment strategies. This pilot study suggests that treatment responsiveness may vary substantially between individual IPF patients, which may partially be due to a differently affected redox status, and further argues that treatment should be personalized to maximize its health benefits .


However, most instruments necessitate the physical presence of a clinician for evaluation, were not designed for PD, nor validated for remote application. (2) Objectives: To develop and validate a self-assessment questionnaire that can be used remotely, and to assess the respondents’ health condition. (3) Methods: A questionnaire, so-called Multidimensional Assessment Questionnaire for Individuals with PD (MAQPD), was developed, administered remotely, and completed by 302 people with PD. MAQPD was validated using factor analysis (FA). The participants’ level of impairment was estimated using factor loadings. The scale’s accuracy was assessed estimating floor and ceiling effects and Cronbach’s alpha. (4) Results: FA suggested classifying the questions into daily activities, cognition, and pain. The respondents did not have extremely severe impairment (most scores ranged from 100 to 180 points), and the factors with the lowest scores were cognition and pain. The instrument had no significant floor or ceiling effects (rates less than 15%), and the Cronbach’s alpha value was larger than 0.90. (5) Conclusion: MAQPD is the only remote self-administered tool found in the literature capable of providing a detailed assessment of the general health status of individuals with PD. Parkinson’s disease (PD) is a complex and progressive neurological disorder that causes tremor, rigidity, bradykinesia, and postural instability . PD has Questionnaires are effective tools for multidimensional evaluation . They ofSeveral instruments are being developed to assess general aspects of health and quality of life in people with PD. However, widely used questionnaires and scales, such as the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) , cannot The Parkinson’s Disease Questionnaire-39 (PDQ-39)  is anothThe Barthel Index  and KatzIn summary, most of the instruments used to assess individuals with PD have the following limitations: they require the physical presence of a clinician to perform the assessment, were not designed specifically for patients with PD, and/or have not been validated to be self-administered or applied remotely. As a result, the need for developing a self-applied instrument capable of being used remotely, which can provide a detailed assessment of the overall health status of people with PD, was identified.The goals of this study were to create and validate the structure of a multidimensional self-assessment questionnaire for people with PD that can be used remotely, to propose a model for calculating the final score and level of impairment of the respondents, to assess the scale’s accuracy, and to identify the most common limitations of individuals with PD.The questionnaire’s development and application were approved by the Ethics Committee for Human Research at the Federal University of Uberlandia.Validated questionnaires and assessment scales such as MDS-UPDRS , PDQ-39 Section A—Research presentation. This section presents the aims of the research, describes the risks and benefits, as well as the importance of the participation of people with PD.Section B—Questions about daily activities (Module 1), related to self-care and the capacity of individuals to live independently; and questions concerning cognitive aspects (Module 2), related to the individuals’ feelings about life and society. This section presents 66 questions for evaluation by the respondents, of which 43 are distributed to the subgroups of Module 1 , and 23 distributed to the subgroups of Module 2 .Section C—Multidimensional Pain Inventory. This section presents four subgroups of questions taken from the MPI (Portuguese version) , which rThe “Multidimensional Assessment Questionnaire for Individuals with Parkinson’s Disease” (MAQPD) questionnaire was proposed, with a total of 83 evaluation questions . The lanMAQPD uses two response scales: a LIKERT scale with five classification levels  used in Section B, and a LIKERT scale with seven classification levels ranging from 1 (little pain) to 7 (a lot of pain) used in Section C. In addition, the questionnaire presents optional open-ended questions so that respondents have the opportunity to express in detail complaints or aspects not mentioned in the questionnaire. The average time it took to respond to MAQPD was 18 min.People with PD were invited to participate in the study through a variety of channels, including email lists, discussion forums, PD webinars, interviews for local television stations, and WhatsApp groups. The inclusion criteria for the study were: Having a confirmed diagnosis of PD from a neurologist or geriatrician; and being able to fill out the questionnaire independently. Individuals whose responses to the questionnaire were incomplete were excluded from the analysis. MAQPD was completed by 310 people, but 8 of them did not have PD. As a result, 302 answers were analyzed.Factor analysis (FA) was used to validate the structure of MAQPD. FA is a multivariate statistical method used to define underlying structures in data matrices. FA investigates the interrelationships between multiple variables in order to derive a reduced linear structure from the original data . As a reIn short, FA can be performed in two stages: factor extraction and factor rotation. Factor extraction involves choosing the number of factors to be extracted, and factor rotation aims to obtain a simple structure to improve data interpretability. One approach to factor extraction is principal component analysis (PCA), which explains correlations by explaining (common) variance .PCA analyzes a data set in which observations are described by several quantitative dependent variables that are intercorrelated. The aim of this method is to express important information extracted from the data set as a set of new orthogonal variables. In addition, PCA represents the pattern of similarity of observations and variables .PCA calculates new variables obtained as linear combinations of the original variables, called principal components. The first principal component is required to have the highest possible variance, and in this way, this component explains the largest part of the data set. The second and others components are computed under the restriction to have the biggest variance possible and to be orthogonal to the previous component. The values of these new variables for the observations are called factors scores, which can be interpreted in a geometric way as the observations projections on the principal components. The number of factors retained can be observed using the Scree Plot ,18.X1 represents the normalized variable on a scale of 0 to 4, and X2 represents the variable on a scale of 1 to 7.First, the data were normalized in order to convert the response scale of Section C to the response scale of Section B. The normalization was done to satisfy the following relationship: a low score indicates severe impairment, whereas a high score indicates less impairment. Equation (1) was used to normalize questions 67 to 78 and 81 to 83, as these items have an inverse relationship with the response scale from 0 to 4. Equation (2) was applied to questions 79–80 because they are directly related to the response scale of 0–4. For both equations, The Bartlett sphericity and Kaiser–Meyer–Olkin (KMO) tests were used to determine whether the dataset met the requirements of FA. The Scree Plot was used to determine the number of retained factors that were rotated (oblimin) to improve their interpretation and relationship with the original variables.Variables with factor loadings less than 0.35 were considered insignificant based on the size of a sample between 250 and 349 individuals .Variables with very similar factor loadings, i.e., difference between factor loadings less than 0.10, in more than one factor .Variables with communality under 0.30 ,21. Low To improve the overall solution of FA, the following criteria were used to exclude irrelevant variables that satisfied at least one of the three criteria:After excluding variables that did not meet these criteria, FA was performed again to re-evaluate the need for additional variable exclusion.FA assigns a factor loading to each item of the questionnaire, which reflects the importance of the item in representing a given factor. To compute the final score for each respondent, the factor loadings were multiplied by the score given by the respondent in each question, and the sum of these values was calculated.The Spearman’s correlation coefficient between variables was estimated to determine whether the proposed model is consistent. The correlation coefficient was classified into four categories: very weak (0.00–0.19), weak (0.20–0.39), moderate (0.40–0.59), strong (0.60–0.79), and very strong (0.80–1.00) .The final scores of individuals were analyzed using descriptive statistics such as mean, standard deviation, median, and minimum and maximum values. These measures were computed for the entire instrument as well as for each of the FA-defined factors. The violin plot was shown, which reveals additional details about the data distribution. To gain a better understanding of the distribution of the respondents’ final scores, the histogram and cumulative distribution function of the entire instrument, as well as the measures of skewness and kurtosis, were examined.The floor and ceiling effects, as well as Cronbach’s alpha, were used to assess the scale’s precision. When a proportion of respondents achieves the lowest possible score across a given domain, the floor effect occurs, preventing the identification of changes in situations where the health condition deteriorates. The ceiling effect is interpreted in the opposite way as the floor effect . When thCronbach’s alpha is a coefficient that can be used to determine whether or not the questionnaire items are homogeneous and whether or not the scale consistently measures the characteristic for which it was designed. If it was larger than 0.75 it was deemed adequate . Floor aThe most common answer  for each question was identified in order to find the basic activities of daily living that the respondents had more difficulty performing, as well as the cognitive and pain aspects most affected in these individuals. The responses from the optional open-ended questions were also evaluated.In addition, the main motor, cognitive, and pain limitations were identified and discriminated for each group of respondents according to their diagnosis time, also calculating the most common answer for each question.As shown in 2 = 28247.25; df = 3403 degrees of freedom; p < 0.001) and KMO test  suggested a good adequacy of the data to FA. The adequacy of the data for the application of FA was verified. The results of the Bartlett’s test of sphericity  and the KMO test . FA was performed once more to ensure that the items in the new MAQPD  met any Three factors should be retained because their proportion of variance explained was larger than 60%  and the FACTOR 1: Comprised of 43 variables related to the activities of daily living (ADL).FACTOR 2: Comprised of 14 variables related to pain.FACTOR 3: Comprised of 14 variables related to cognitive aspects.Oblique rotation oblimin was used to improve the interpretation of the factors, and the variables were reorganized into three different groups:No other variables needed to be excluded.The factor loadings of each questionnaire item are shown in The model in Equation (3) was used to compute the sum of each respondent’s final score.Individuals’ final scores could range from 0 to 209.36 points if they answered “0” and “4” to all questions, respectively, according to the model. In addition, the lower the score, the more impaired the individual is.The histogram and cumulative probability distribution function of the individuals’ final scores are depicted in The frequency distribution of the data is shown by the histogram. Most scores ranged from 100 to 180 points, and only a few people had low scores, i.e., less than 50 points. The cumulative distribution function expresses the likelihood that a random observation sampled from the population will be less than or equal to a given value. The probability of an individual’s final score being between 100 and 180 points was approximately 62 percent, and the probability of the score being less than half of the possible score (approximately 105 points) was approximately 30 percent. The skewness was −0.37 and the kurtosis was −0.30.There were no significant floor or ceiling effects found, with values ranging from 0.28% to 10.85%. Cronbach’s alpha was larger than 0.90 for all dimensions, indicating that the proposed questionnaire has strong internal consistency.According to the responses, the activities of daily living that people with PD had more difficulty which were represented by Question 13 with a prevalence of zero, indicated that most people completely disagree with the statement; and Question 16 with a prevalence of one indicated that most people disagree with the statement.The most affected cognitive aspects in patients are represented by the following questions: 48, 49, 50, and 51, which are about living with family and society; 53 and 54, which are about an individual’s personality; 55 and 56, which are about energy and mood; and 63 and 64, which are about emotion and feeling. All of these questions had a score prevalence of one.In terms of pain, the following questions indicate the most impairment of the individual: 67, 68, 72, 76, and 83. All questions had a prevalence of scores equal to one.Additionally, 41.39% of the respondents answered the open-ended questions. Of these, most reported problems in performing household chores, such as washing dishes, cleaning the house and cooking.This work was created in response to the lack of an instrument for remotely assessing the health of people with PD. A study  emphasizMotolese et al.  aimed toFirst, the questionnaires applied by Motolese et al.  were notMAQPD was developed on the basis of existing assessment instruments. It was answered by a large number of people with PD, which contributed to a more robust validation of the instrument structure using FA. This method was used to verify each question’s contribution to the multidimensional evaluation and to group questions into latent dimensions, implying a better distribution and arrangement of the questions ,17. FA sThe estimate of factor loadings from FA enabled weighing the final scores based on the relevance of the question to define the factor. Correlation coefficients ranging from 0.54 to 0.89  were estThe final scores for the entire MAQPD were higher than the measures for the three domains, as expected, because the instrument contains 71 questions in total, while the subgroups of questions related to ADL, cognition, and pain contained 43, 14, and 14 questions, respectively . The relWhen compared to pain, the scores for cognition questions were lower . This meThe data distribution  reveals The skewness and kurtosis coefficients of −0.37 and −0.30, respectively, indicate that the final scores had higher values and were dispersed, indicating a sample with lower impairment but not homogeneous (various diagnosis times).Floor and ceiling effects were not found in statistically significant proportions across the entire instrument or across any domain . As a reQuestion 13—“I drive without difficulty” was the only one in the whole questionnaire that presented a prevalence of answer equal to zero, meaning that most individuals responded to this statement that they totally disagree. In this case, a physiotherapist can direct a rehabilitation session that focuses on specific exercises for alleviating the symptoms that prevent the patient from performing the activity, i.e., driving. Therapies may improve specific functions, allowing the activity to be performed again by the individuals.Furthermore, it was determined that approximately 71.43% of the questions pertaining to cognitive aspects had a prevalence of answers equal to one. This indicates that the majority of respondents had issues with social and family coexistence, lacked the energy and motivation to develop routine activities, and struggled to control their emotions . It is nRegarding pain, 35.71% of the questions presented prevalence of answers equal to one (a lot of pain), one of them being question 76—“How much did your pain affect your ability to do housework?”. This result is associated with that obtained by the open-ended questions, for which most of the respondents answered that they had difficulties in performing housework, suggesting that one of the reasons why individuals feel difficulties in performing domestic chores is pain.Individuals with a diagnosis time of less than 2 years, for example, reported that they had great difficulty in dancing, and that they suffered from a variety of problems related to cognitive issues. For these individuals, doing activities that exercise balance, as well as therapy sessions, may be effective ways to solve these problems. In addition, individuals with a diagnosis time between 2 and 4 years reported that they had difficulty in driving and that they did not meet their friends as much as they would like. Possibly, training the body movements that affect driving—either by using a serious game in which the player is stimulated to drive virtually, or with conventional physiotherapy—may contribute toward the individual performing this activity more easily. Furthermore, promoting support groups with social activities in therapy centers, as well as informing friends and family members about the issue related to social interaction, may help to improve the conviviality of these individuals.Additionally, as individuals with diagnosis time of less than 2 years, between 6 and 8 years and more than 10 years had lack of social interaction, mood changes, and/or lack of disposition, performing a physical activity that requires relating to other people, e.g., dancing, becomes an extremely complex task. These findings agree with those reported by Darweesh et al. . These mA different consideration that also should be highlighted is that all groups presented limitations related to cognitive aspects, which indicates that this domain needs a more attentive and careful look by family members, health professionals, and researchers. In addition, with the exception of the group with diagnosis time of less than 2 years, all the other groups reported problems related to pain. Possibly, improving aspects related to cognition may contribute to reducing the pain experienced by individuals, since one may entail the other.The results of an evaluation based on multidimensional questionnaires contribute to a comprehensive understanding of the individual’s health status, as well as their true limitations and needs ,5. UnderA questionnaire, so-called MAQPD, was developed and its structure was validated by using FA, which allowed for grouping the questions into three domains: ADL, cognition, and pain. The final score for each respondent was calculated using the factor loadings as the weight of the questions. The respondents did not present an extremely severe level of impairment. As the instrument did not present substantial floor or ceiling effects, it can measure both the clinical worsening and improvement of the respondents. The ADL that respondents had the most difficulty in performing was driving. Pain and cognition were also relevant aspects.In conclusion, the MAQPD is the only self-administered questionnaire found in the literature capable of being used remotely, and which can provide a detailed assessment of the general health condition of people with PD.


Staphylococcus aureus ATCC 25293, Escherichia coli ATCC 25922, Candida albicans ATCC 10231. Effective bactericidal activity of PCL with small amount of GNP, especially against C. albicans and S. aureus was confirmed. A decrease in this property or even multiplication of microorganisms was observed in direct proportion to the graphene content in the samples.This work contains an analysis of the impact of modifying a bioresorbable polymer—polycaprolactone (PCL)—with various additives on its antibacterial properties. To this end, samples of PCL filament containing various content levels of graphene (GNP), 0.5%, 5%, 10%, were obtained using injection molding. Polymer samples without additives were used for comparison. The next step was to assess the antimicrobial impact of the preparations under study against the following microorganisms:  Polymers are a very important group of materials used in modern medicine. Polymers are used as scaffolding materials for artificial skin and tissue engineering. Polymers are also used in carrier formulations for transdermal and transdermal drug delivery. Polycaprolactones (PCLs) are used in a wide range of applications due to their properties ,2. Both One of its main advantages is biodegradation ,4, the dSpecific polymers offer a wide variety of possibilities for specific uses in biomedical applications. There are various methods of producing PCL implants, such as solvent casting, foaming, electrospinning, phase separation, or molding ,8. The sPolycaprolactone is a biocompatible, nontoxic aliphatic polyester that can be degraded by hydrolysis of its ester linkages in physiological conditions, and it is approved by the FDA for biomedical applications. It is especially very interesting for the preparation of long-term implantable devices and is widely used in long-term implants and controlled drug release applications.Polycaprolactone possesses some antibacterial properties ,11. ThisMany researchers indicate the need for PCL modifications that increase its bactericidal effectiveness. PCL itself can be a carrier of antibacterial substances ,13. Its Graphene is an advanced material which successfully finds application in medicine. Biomedical applications of graphene and its composites include its use for gene delivery and small drug molecules. In addition, it is used for biofunctionalization of proteins, anticancer therapy, and as an antimicrobial agent for bone and dental implants. One of its characteristics is antibacterial properties . All aspDue to its physical and chemical properties and biocompatibility, graphene and graphene oxide can be used as innovative biomedical materials for biodefense, drug distribution in the body, neo-biotherapy, regenerative medicine, and implant surgery. However, graphene-based nanomaterials can be biocompatible or toxic to living cells. The response of biological cells to these nanomaterials depends largely on the number of layers, lateral size, purity, dosage, surface chemistry, and hydrophilicity.S. aureus, E. coli, and C. albicans were used in the study. The materials intended for research were the filaments sticks manufactured for the 3D printing technique.This work presents a comparative analysis of the bactericidal properties of polycaprolactone samples with the addition of varying content of graphene in the form of nanoparticles (graphene nanoplatelets) (GNP). Typical human pathogens—Graphene nanoplates (GNPs) used as fillers consist of sheets of graphene with a total thickness of several nanometers. SEM images of the introduced GNPs are presented in The lowest graphene concentration selected was 0.5 wt%, an intermediate value of 5 wt%, and the maximum concentration used was 10 wt%.Polycaprolactone blends were prepared containing 0.5, 5, and 10 wt% of graphene content. PCL filaments in the form of composite sticks, for further 3D printing, were made using the injection molding method . Three tAs opposed to pure PCL, the PCL/GNP sticks exhibited a more irregular surface caused by the GNP present on the surface a,c,e. InThe SEM (Scanning Electron Microscope) micrographs of the obtained samples were compared with the same magnification X500, X1000, X3000, and X50000. Small agglomerates of graphene formed by sheets were observed on the surface of all modified filaments .C. albicans.Negative controls—normal . Positive controls—normal . The number of observed microorganisms expressed in the form of the CFU number after 17 h of incubation and the resulting antibacterial efficacy (ABE) are both presented in In the charts , the sumMacro- and microscopic evaluations were performed. The results indicate that graphene nanoparticles were successfully incorporated into the polymer filaments. Higher GNP concentration caused an increase in particle agglomeration. A detailed description of the process parameters and the influence on the properties of the obtained materials was presented in our earlier publication . The resS. aureus and C. albicans. However, this effect appears to decrease with increasing graphene content. We found no antimicrobial effect at all against E. coli.The results show a significant antimicrobial effect against S. aureus, PCL without additives shows only slight antimicrobial activity at the 30% ABE level. Modification with a small amount of graphene (0.5%) significantly increases the antimicrobial efficacy, reaching a level of 90% ABE. Further increasing the graphene content significantly reduces and suppresses the antimicrobial properties of PCL. Several authors emphasized that graphene exhibits antimicrobial properties in the form of oxides [In the case of f oxides . The strDuring sample preparation, polymer granules were dry-mixed with GNP powder. It is highly likely that the carbon particles precipitated during the preparation of the culture suspension served as food for the cultured bacteria. However, we concluded that adding only a small amount of graphene (0.5%) to the PCL samples significantly increased their antimicrobial efficacy compared to pure PCL, and further increasing the graphene content effectively reduced the antimicrobial effect.E. coli. In all cases, the inoculated suspensions induced confluent growth of these bacteria. However, a number of researchers confirmed that PCL shows activity against E. coli, but only if the polymer is modified, for example, by silver nanoparticles [None of the tested samples showed activity against articles ,25.C. albicans: for PCL, the average ABE was about 98%; when GNP was added to PCL, this value dropped to 68%. Increasing the content of graphene in the samples effectively reduced the antimicrobial activity. This may be due to the fact that carbon particles present in the suspension can become food for bacteria, through a similar process as in the case of Staphylococcus aureus.PCL and PCL/GNP_0.5 showed significant antimicrobial activity against This research employed polycaprolactone,  and graphene nanoplatelets . In order to produce filaments for further 3D printing, polymer blends with additives and pure PCL granulate were prepared. The polymer granules were dry mixed with GNP powder to obtain 0.5, 5, and 10% by weight of graphene content in the blend. After combining the ingredients, each of the mixtures was mixed in a mechanical mixer for 20 min. Filaments in the form of modified sticks were manufactured in the process of injection molding using a BabyPlast 6/10P  injection molding machine. The parameters of filament production were described in the work . Microstructural analyses to assess the surface of all samples were carried out in a Nova NanoSEM 200 FEI  scanning electron microscope. All the samples were placed on a stainless-steel plate and covered with a carbon thin film by sputtering to avoid the electrostatic charge accumulation. Filaments in the form of sticks were evaluated using a stereomicroscope from the OPTA-TECH company , equipped with a CMOS 3 camera and OptaViewIS software version 4.3.0.6001. For microbiological tests, filaments were cut and bars with dimensions of 1.75 mm × 6 mm were prepared as shown in (1)Staphylococcus aureus ATCC 25293(2)Escherichia coli ATCC 25922(3)Candida albicans ATCC 10231Polycaprolactone sticks with the addition of 0.5, 5, and 10 wt% graphene were evaluated for bactericidal activity against three selected reference microbial strains:5 CFU / ml in tryptone water . The positive control was the volume 2 mL of a suspension of a given reference strain of microorganism in tryptone water, whereas a negative control was 2 mL of tryptone water. After 17 h of dynamic incubation  at 37 °C (S. aureus and E. coli) or 35 °C  from each test sample and control, 20 μL of the suspension was plated on a solid culture medium: Columbia agar with 5% sheep blood (S. aureus), Mac Conkey agar (E. coli), or Sabouraud agar . After 24 h of incubation at 37 °C (S. aureus and E. coli) or 48 h incubation at 35 °C , the observed microbial colonies were counted using the automatic colony counter “aCOLyte”  to determine bactericidal efficacy  or fungicide  of the tested preparations [All stages of microbiological tests were carried out in accordance with the principles of asepsis and antiseptics. Each preparation was tested in each replicate with four replicates. A single sample of the test preparation was placed in a 2 mL suspension of the standard strain of the microorganism with a final density of 1.5 × 10arations ,27.The use of PCL polymers is widespread in modern medicine. Appropriate modifications of this polymer can enhance its basic properties: in this case, the antimicrobial effect. Adding a small amount of graphene can significantly improve these properties.The results of our research show that increasing the content of graphene in the excipients reduces their bactericidal effect or increases the multiplication of bacteria. It is essential that the newly created biomaterials must always be analyzed in detail. Although the base ingredients separately have good bactericidal properties, their combination may reduce this effect.The bacteria which were selected in our work, constitute a saprophytic flora in humans ,29,30. H


Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS. Methods: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022. Results: Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, met the inclusion criteria for our meta-analysis. According to the random-effects model, CSF TDP-43 levels are higher in ALS patients compared with control groups. Conclusions: CSF TDP-43 could represent a biomarker of ALS, but further studies are mandatory before drawing conclusions. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of both upper and lower motor neurons . On average, patients with ALS suffer from progressive muscle weakness leading to respiratory failure and death within three to five years ,2. AccorTwo forms of the disease are known, sporadic, occurring in 90% of ALS cases, and familiar, due to mutations in more than 20 genes, including hexanucleotide expansions in chromosome 9 open reading frame 72, superoxide dismutase 1, TAR DNA-binding protein 43, fused in sarcoma and TANK-binding kinase 1 ,7. The fAt present, the diagnosis of ALS is primarily clinical and represents a challenge for clinicians. Specifically, there is no marker or procedure to establish the diagnosis of ALS reliably. The diagnosis is reached through several clinical examinations and diagnostic tests to rule out diseases mimicking ALS. According to El Escorial/Airlie House Criteria , the ALSWith the number of cases expected to rise to nearly 400,000 worldwide by 2040 , ALS repThe ideal biomarker of ALS should reflect the pathophysiological mechanism of the disease. A characteristic feature of degenerating motor neurons in ALS patients is the presence of the cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43). TDP-43 is a protein of 414 amino acids, encoded by the TARDBP gene, belonging to the family of heterogeneous nuclear ribonucleoproteins, a group of proteins involved in RNA processing .It is abundantly expressed in systemic organs, such as the central nervous system, pancreas, and spleen. Physiologically, it is localized in the nucleus but under stress conditions, a hyperphosphorylated, ubiquitinated, and cleaved form of TDP-43 aggregates in the cytoplasm, causing axonal swelling and impairing mobility ,14,15. RWe performed a systematic review and comprehensive meta-analysis to investigate whether TDP-43 levels in cerebrospinal fluid (CSF) could be a reliable biomarker of ALS.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines 2020 . All stuTwo reviewers (CMG and AMC) systematically and independently performed a comprehensive electronic search of PubMed and Web of Science. The following medical subject heading (MeSH) terms “TAR DNA-binding protein 43” OR “TDP-43” AND “Amyotrophic Lateral Sclerosis” OR “ALS” AND “CSF” OR “plasma” were used to search articles. No publication date restriction was applied, and the end-date of our search was 08 April 2022.the manuscript describes a retrospective and prospective study design;it was written in the English language;the study must provide a full description of the method used to measure TDP-43 levels;the study must use TDP-43 as a biomarker in the blood or CSF to differentiate ALS patients from a control group;the study must use a quantitative method for TDP-43 detection;the study must provide sufficient data to calculate the outcome.The inclusion criteria were: evaluation of only the prognostic role of TDP-43;studies without healthy controls or without disease control;letters, case reports, animal studies, reviews, and meta-analyses;languages other than English;qualitative method for TDP-43 detection;full text not found.Exclusion criteria were: Two authors (CMG and AMC) independently collected data referring to the study and patient characteristics. The extracted information from each study included the first author’s name, the year of publication, country, study design, clinical setting, study population, sample, the method used, and outcome data (area under the curve (AUC), sensitivity, specificity, and cut-off).n was the sample size.For each study, the standardized between-group mean difference (SMD), calculated as the difference in means between ALS and controls divided by the pooled standard deviation (SD) of both groups, was used as effect size . A smallA random-effects model was used to pool effect sizes. The restricted maximum likelihood estimator  was usedThe study selection process is schematically presented in the PRISMA flow diagram . A totalThe main characteristics of the studies included in the meta-analysis are described in We used the QUADAS-2  criteria to assess the quality of seven papers selected for systematic review . This toThe restricted maximum likelihood method estimated a between-study heterogeneity variance of tau^2 = 0.27 (95%CI 0.06–1.54). The I^2 index was 79.2% (95%CI 57.4%-89.9%), suggesting substantial heterogeneity.p = 0.024), indicating that TDP-43 in CSF was higher in ALS patients than in controls. According to the random effects model, the pooled effect was g = 0.66, with the 95%CI ranging from 0.12 to 1.20. The effect was statistically significant (p = 0.224) or Begg’s test (p = 0.177).No publication bias was detected by either Egger’s test (Since its discovery fifteen years ago, several pieces of evidence from clinical and experimental studies have revealed the pathogenic role of TDP-43 in ALS. It is now widely known that it binds to UG-rich repeats of target RNAs, and it has a pivotal role in regulating mRNA transcription, splicing, transport, and stability. Under physiological conditions, TDP-43 is expressed in the nucleus and can shuttle between nucleus and cytoplasm . HoweverIn this systematic review and meta-analysis, we evaluated the usefulness of CSF TDP-43 as a biomarker of ALS by analyzing results from seven studies, including a total of 472 individuals, 254 patients with ALS and 198 controls. We found that CSF TDP-43 was significantly increased in ALS patients compared with controls. The difference among sample means was standardized by the pooled standard deviation, since standardization makes it much easier to evaluate the magnitude of the mean difference. Following the conventions by Cohen , the pooThe research in the field of ALS biomarkers is hampered by several factors, including the rarity of the disease, the delayed diagnosis, and the high rate of misdiagnosis. While improvements in biotechnology have led to significant progress for several neurological diseases, such as Alzheimer’s disease ,40,41, tCurrently, studies on CSF TDP-43 in ALS are highly heterogenous in terms of sample size, the analytical assay used for measuring the biomarker, and inclusion and exclusion criteria for patients and, especially, for controls. Indeed, some authors included healthy individuals ,28, whilA few studies evaluated the concentration of TDP-43 in plasma, achieving inconsistent results. This could be partially explained by the analytical methods used. Indeed, most authors measured TDP-43 by ELISA, and the commercially available kits have insufficient sensitivity to detect circulating TDP-43. The Simoa analyzer has better analytical performance with a 100- to 1000- higher sensitivity than ELISA. Kasai et al., by measuring TDP-43 using Simoa analyzer in a cohort of 29 ALS patients and 29 age-matched controls, found increased levels of the biomarker in both the CSF and plasma of ALS patients . AlthougIn conclusion, in this meta-analysis we evaluated only CSF TDP-43 and not plasma, since the number of studies was too low. Overall, the findings of this meta-analysis encourage further studies to validate the possible role of TDP-43 as a biomarker of ALS.Some limitations of this study should be cited. First, we performed the statistical analysis on a small number of studies and each study included a small sample size. Additionally, different analytical methods and, consequently, different concentrations were reported in the included studies.


The present study investigates the possibility of obtaining graphene-like phases  as fine suspensions by applying a novel pulsed laser ablation (PLA) approach in flow mode. Two types of suspensions of microcrystalline graphite in aqueous suspensions and two types of microcrystalline graphite in suspensions of 6% hydrogen peroxide solution were irradiated in a quartz tube through which they flow. The third (λ = 355 nm) and fourth harmonics (λ = 266 nm) of an Nd:YAG laser system (15 ns pulse duration and 10 Hz pulse repetition rate) were used. The morphology of the obtained particles was studied by transmission electron microscopy (TEM). Their phase composition and structure were explored by X-ray photoelectron spectroscopy, X-ray diffractometry, and Raman spectroscopy.  Pulsed Laser Ablation in Liquid (PLAL) has been proven as a simple and effective technique to fabricate the different types of carbon-related nanomaterials including nanodiamonds, few-layer to multilayer graphene nanosheets, and graphene oxide nanosheets . SystemiThe use of PLAL for the synthesis of carbon materials is chemically and technically very simple. Almost no byproducts are created and no catalyst is used. Many sources of carbon can be used as the starting material.There are three main types of PLAL techniques used to synthesize carbon nanomaterials.The first experimental design of PLAL included a focused laser beam directed on the surface of a solid target immersed in a liquid for generating the colloidal carbon nanomaterials: nanodiamonds and quantum dots ,9, as weFurther on, the solid target is replaced with a suspension , which significantly increases the useful yield in the form of stable suspensions of nano-sized carbon phases in water . The laAnother implementation of PLAL uses a jet stream of a suspension of carbon particles irradiated by a focused laser beam . The colThe present research examines the opportunity of obtaining graphene-like phases  and studies their modification and oxidation level when applying a pulsed laser ablation in liquid (PLAL) in flow mode.The phase composition of the obtained sedimented suspensions was characterized by different methods: X-ray photoelectron spectroscopy (XPS), grazing incidence X-ray diffractometry (GIXRD), Raman spectroscopy, and transmission electron microscopy (TEM)2O2 in bidistilled water) was used in the other suspension as the liquid medium, maintaining a concentration of 4 mg/mL solid to liquid in all experiments of this study. The suspensions were prepared and placed in an ultrasonic bath 30 min before irradiation.Two different types of suspensions based on two graphites, 99.9995% purity Ultra F , designated as HQ, and low-grade graphite , designated as LQ, which were obtained by mixing 0.4 g of graphite in 100 mL of bidistilled water. Hydrogen peroxide solution  were close to the maximum and minimum absorption values shown; therefore, the radiation was absorbed by all phases of the suspension at λ = 266 nm and mainly by the graphite phase at λ = 355 nm. The irradiation of the entire suspension lasted about 15 min. The obtained graphene-like phases were about 8–11% of the mass of the starting graphites, but we must note that part of the modified particles agglomerated with the main phase and settled. Irradiation took place in an environment isolated from atmospheric air, which, combined with a suitable liquid medium, enabled not only the preparation of different carbon phases but also the realization of their effective functionalization, which is an advantage over other PLAL methods. For the implementation of this method of laser ablation in liquid, no complicated equipment is needed, and there are no moving parts. This makes the PLAL in flow mode method highly reproducible and very easy to apply.−1 or better. The X-ray photoelectron spectroscopy (XPS) analyses were carried out using an ESCALAB MKII spectrometer with a non-monochromatic Al X-ray source under vacuum greater than 10−8 Pa at a 45° take-off angle. The Au4f photoelectron line was used for the calibration of the spectra. The accuracy of the measured BE was 0.2 eV. The photoelectron lines of the constituent elements on the surface were recorded and corrected by subtracting a Shirley-type background and quantified using the peak area and Scofield’s photoionization cross-sections. The C1s, O1s, and Auger lines were recorded for each specimen and further on, the C1s lines were subjected to an additional fitting procedure with XPSPEAK 4.1 software.The Raman measurements were carried out using backscattering geometry with a micro-Raman HORIBA Jobin Yvon Labram HR 800 visible spectrometer equipped with a Peltier-cooled CCD detector with a He-Ne (633 nm wavelength and 0.5 mW) laser excitation. The laser beam was focused on a spot of about 1 μm in diameter, the spectral resolution being 0.5 cmThe structure of the suspensions after drying was characterized by XRD using a PANalytical Empyrean apparatus, whereas the local morphology and structure were revealed by a high-resolution transmission electron microscopy (HR TEM) characterization in both high-resolution (HR) and selected area electron diffraction (SAED) modes with an HR STEM JEOL JEM 2100 microscope.There is always an amount  of unmodified graphite particles in the resulting suspensions, which settle up to 5 min after the laser treatment and are removed from the remaining suspension by decantation. The suspension obtained after decantation was sufficiently stable over time: visible precipitation occurred after more than 24 h. For further research, powders obtained after drying the decanted suspension at 50 °C were used. In a control experiment, suspensions prepared in the manner described were examined without being irradiated and showed results consistent with those of pristine graphite.2 and sp3), structure, and defects  of carbon materials [XPS analysis is useful for identifying the chemical composition, hybridization , sp3-, hydroxyl C–OH/epoxy groups, C–O–C functional groups, and π-π* bond. The C–H bond and oxygen-containing bonds were formed due to the presence of edge and defect sites in the graphite, which provided suitable anchoring sites for the functionalities [2-hybridized C atoms arranged on the corner of a hexagon as in graphite. The peak at ∼285.4 eV corresponds to sp3-hybridized carbon atoms and likely originated from unsaturated carbon atoms reacting with hydrogen during the oxidation process. An increase in the oxygen content on the surface of HQ graphite was observed after laser treatments in H2O, as well as in H2O + 6% H2O2 for both laser wavelengths compared to the pristine one. The calculated sp3/sp2 ratio did not change drastically  [Additionally, in the spectra appeared shake-up satellite peaks in comparison with the pristine one in the high-binding energy range (higher than 292.0 eV). The peaks that appeared at higher-binding energy regions can be associated with the formation of Ces (CNT) .2O2 with 266 nm, seven peaks acted, situated at around 284.8 eV, 286.3 eV, 288.0 eV, 289.5 eV, 291.0 eV, 295.0 eV. In addition, two other peaks appeared at around 282.0 eV and 283.9 eV. The shoulder appeared at around 282.0 eV, most probably due to a charge-neutralized fraction due to the existence of hydrocarbon [2O and H2O2 caused similar changes in the C1s photoelectron line. Only four peaks were used for the fitting of C1s to H2O; however, seven peaks were used for the fitting of C1s to LQ graphite in the H2O2 suspension. Again, the laser treatments of H2O led to the formation of GO, and the same laser treatment of LQ graphite in H2O2 led to the formation of rGO. Furthermore, the peaks that appeared higher than 292.0 eV in the C1s spectra were associated with the formation of C60 and CNT [2 or sp3 features in carbon-like materials [2 bonds, whereas the slopes of the spectra for the other samples gradually changed and tended to that of the sp3 bond, especially for the laser-treated suspensions prepared with LQ graphite , the intensity of the G- and 2D bands decreases. It should also be noted the formation of:-2O2, modified by laser irradiation with a fluence of 0.364 J/cm2;a very fine crystalline (or semi-amorphous) phase of GO  bands , which were associated with the enrichment of graphene/graphite phases with oxygen-containing radicals [−1, whereas the intensity of the 2D band was comparable to that of the G-band. It should be noted that such flakes were observed more frequently in suspensions irradiated with a 355 nm laser wavelength.In contrast to the suspensions discussed above, a large variety of graphene-like phases  were observed in those of LQ graphite in bidistilled water and bidistilled water with 6% Hradicals . SimilarThe XRD patterns obtained from pristine HQ graphite ((002) graphite reflection (COD # 96-101-1061) intensity decreased several times (more than eight times) after the PLA process using 355 nm and fluence of 0.465 J/cm2 in HQ graphite suspensions. Moreover, the addition of 6% H2O2 to the initial suspension of graphite HQ in water further reduced the peak by more than 50%. In parallel, the same peak practically did not change its position but significantly increased its full width at a half maximum (FWHM). The increase in this parameter in those treated with radiation with a wavelength of 266 nm was more than 50% in both suspensions. The same parameter (FWHM of d(002) reflection) determined in the XRD patterns of the suspensions modified with a wavelength of 355 nm increased by 35% in the suspension in bidistilled water and by 63% in that in a solution of hydrogen peroxide in bidistilled water. The above results undoubtedly show that PLA processes cause fragmentation of graphite particles, which most likely takes place by the exfoliation of single- to multilayer graphene and its further agglomeration during sedimentation. The treatment increased the width of all reflections, whereas some reflections disappeared. This allowed us to conclude that a process of amorphization was taking place. The dFor LQ graphite, there was a decrease in the reflection intensity and an increase in the width after the PLA process. The detailed analysis of these results did not differ significantly from that already conducted for the 266 nm- and 355 nm-modified suspensions of the same material in water in a non-flow system . By analThe specimens for the TEM studies were prepared by dropping and drying a drop of any suspension obtained on formvar-covered TEM grids. It should be emphasized that due to the method of obtaining the samples, the visualized nano-sized objects were stuck to each other despite the sonication of the suspension prior to the immobilization on the grid Thus, agglomerates of a much larger size were formed, and individual single-layer graphene flakes were very rarely observed. 2O2 in water, which probably caused a decrease in the crystals after treatment with the H2O2 solution. Amorphous material was detected in the LQ graphite sample even before the H2O2 treatment. Additionally, the TEM characterization of all the suspensions studied showed the formation of different phases after the PLA processes depending on the initial graphite and the composition of the liquid phase of the suspensions:(i)2O2 in water solutions. The graphene/graphene-like flakes were usually stuck to each other.Graphene and defected graphene flakes, 2O2 in water solutions, as well as more frequently in suspensions of LQ graphite. Aggregates of C60 were observed in all suspensions.Bundles of 2D (mainly graphene and graphene-like flakes stuck together with fullerene C60), as shown in (iii)Sedimented agglomerations of amorphized carbon phases surrounded by 2D (graphene and graphene-like flakes or C60 fullerenes arranged in 2–3 layered nanostructures), as well as 3D (carbon nanoparticles up to 10 nm in size or fullerenes C60), nano-sized particles see .60 fullerene (COD # 96-800-0216)  see a. The di216) see b corresp-60 (COD # 96-800-0216) (see 60 (COD # 96-800-0216)  3D particles sedimented on the amorphous particles. These 3D particles were almost spherically shaped a and pos216) see b, with H216) see c. Spheri-60 (COD # 96-101-1061 and COD # 96-800-0216). These agglomerations were observed in HQ graphite suspensions in H2O irradiated with a λ = 266 nm wavelength only.Relatively large formations (size larger than 500 nm) with an irregular form and amorphous structure Practically completely amorphized graphitic carbon see . Such pa2O2 solution as a model system. It has been shown that irradiated suspensions containing mainly nanoscale carbon phases  and bundles of graphene-like flakes) can be produced by this method using laser-beam wavelengths of λ = 266 nm or 355 nm. The new approach for PLAL enables us to effectively achieve the desired degree of functionalization of the processed carbon materials with different types of atoms since the irradiation is carried out inside a quartz tube, isolated from the environment. The ability to control the medium, flow rate, laser wavelength, and irradiation energy flux enables the wide use of this technique. Finally, established flow-mode PLAL procedures have been found to be reproducible, and the main advantages of the proposed method are its simplicity, ease of application, and ability to synthesize large amounts of nano-sized carbon phases, as well as the opportunities it provides for effective functionalization.This work investigates a proposed new method for PLAL in flow mode of an aqueous suspension of microcrystalline graphite, as well as in a flow of microcrystalline graphite, in a 6% H


As deformation and defects are inevitable during the manufacture and service of graphene resonators, comprehensive molecular dynamic (MD) simulations are performed to investigate the vibrational properties of the defective single-layer graphene sheets (SLGSs) during tension. Perfect SLGSs, SLGSs with single vacancy, SLGSs with low-concentration vacancies, and SLGSs with high-concentration vacancies are considered, respectively. The frequencies of the perfect and defective SLGSs at different stretching stages are investigated in detail. The effects of different external forces are also taken into account to study the vibration properties of the defective SLGSs. Results show that the perfect and defective SLGSs both successively perform four stages, i.e., the elastic stage, the yield stage, the hardening stage, and the fracture stage during stretching, and the elastic properties of the SLGSs are insensitive to the vacancy defects, while the ultimate strain is noticeably reduced by the vacancies. The single vacancy has no effect on the vibration properties of SLGS, while the frequency decreases with the increasing vacancy concentration for SLGS at the elastic stage. The frequency of yielded SLGS with a certain vacancy concentration is almost constant even with a varying external force. The two-dimensional 2D) nanomaterial with a monatomic layer, graphene, has attracted significant attention from the scientific and industrial communities since its first isolation in 2004. Due to its extremely high mechanical, electrical, optical, and thermal properties, graphene has been considered an ideal material for use in nanoelectromechanical systems (NEMS) D nanomat,4,5,6, wSimilar to other known materials, perfect graphene sheets are almost impossible to manufacture, even when fabricating experimentally. It is quite well known that defects in materials have a great influence on the properties of crystals and nanostructures ,16,17,18In order to understand the vibrational properties of graphene nanoribbons at different tensile conditions, this paper treats the graphene nanoribbon as a finite-length pre-strained SLGS with clamped ends. The originality of the present work includes: (1) The tensile performances of SLGSs with different vacancy concentrations are studied, (2) the SLGSs with varying pre-strained degrees are taken into consideration to analyze their vibrational properties. We, first, perform extensive MD simulations to analyze the tensile characteristics of the finite-length SLGSs with different vacancy defects, and then study their natural frequencies with varying pre-strained degrees. The effect of different external loads on the resonant response of the pre-strained SLGS with clamped ends is also analyzed to ensure the safety of the graphene nanoribbons. All the calculations related to this work were done by the large-scale atomic/molecular massively parallel simulator (LAMMPS) an open-source molecular dynamic software on Windows .L = 10.365 nm, thickness h = 0.335 nm, and width W = 3.24 nm, including (a) perfect sheet, (b) single vacancy, (c) low-concentration vacancies, and (d) high-concentration vacancies SLGSs. Three layers at both ends, colored in red, of all the SLGSs are fixed, while the rest are free parts that are colored in blue. A periodic boundary is used in the X and Y directions, and a shrink-wrapped boundary is used in the Z direction.In the MD simulations, the adaptive intermolecular reactive empirical bond order potential (AIREBO) is adopted. As given in detail in Stuart et al. , the AIRractions .−1 is implemented along the positive X-axial until the graphene nanoribbons collapse. The strain increment is applied after every 1000-time steps. The Velocity–Verlet algorithm and Nosé–Hoover thermostat are used.Each model is initially relaxed using canonical ensemble (NVT) simulation until the energy of the system is fully minimized for a specified temperature of 100 K, then axial strain applied. The deformation-control method with a strain rate of 0.0005 psAfter computing and exporting the stress and geometrical characteristics of the defective SLGSs during tension through the LAMMPS codes, the tensile stress-strain curves of the SLGSs with different vacancy concentrations are obtained, as shown in To explain the vacancy sensibility, f  per atom  by selecting the kinetic energy of the systems as time-domain signals. In summary, extensive MD simulations are performed to understand the tensile strength of finite-length graphene nanoribbons with varying vacancy concentrations and their vibration properties at different stretching states. The graphene nanoribbon is simulated by SLGS. Perfect SLGSs, SLGSs with a single vacancy, SLSGs with low-concentration vacancies, and SLSGs with high-concentration vacancies were considered. Through the tensile stress-strain curves, all the SLGSs with different vacancy concentrations went through the four stages, i.e., elastic stage, yield stage, hardening stage, and fracture during the tensile process. The vacancies have a greater influence on the ultimate strain of the SLGSs, than the elastic limit and yield limit. As for the vibrations of the defective SLGSs, different external forces are respectively applied to investigate their resonance frequencies at different stretching stages. Even the single vacancy had no effect on the vibrational properties of the SLGSs, the increasing vacancy concentration decreases the resonance frequencies of the SLGSs at the elastic stage. The frequency of yielded SLGS with a certain vacancy concentration is almost constant even with a varying external force.