It has been observed that the Dirac cones can be easily shifted along the symmetry lines without breaking the degeneracy. We have attained two different conditions based on the sole relations of hopping parameters and on-site energies to break the degeneracy. Further, in order to perceive the topological aspect of the system we have obtained the phase diagram and Chern number of Haldane model. This exact analytical method along with the supported DFT computation will be very effective in studying the intrinsic behaviour of the Dirac materials other than graphene.Present work reports an elegant method to address the emergence of two Dirac cones in a non-hexagonal graphene allotrope S-graphene (SG). We have availed nearest neighbour tight binding (NNTB) model to validate the existence of two Dirac cones reported from density functional theory (DFT) computations. Besides, the real space renormalization group (RSRG) scheme clearly reveals the key reason behind the emergence of two Dirac cones associated with the given topology. Furthermore, the robustness of these Dirac cones has been explored in terms of hopping parameters. As an important note, the Fermi velocity of the SG system ( In particular, the exceptionally high carrier mobility of graphene lies in the fact that the dynamics of charge carriers is governed by the Dirac equation3. Furthermore, these gapless Dirac cones in graphene are robust under some of the external perturbations viz. structural deformation or chemical functionalizations5. However, the only dispute that restrict the potential application of graphene in modern opto-electronic devices is its zero band gap nature7. Afterwards, a plethora of investigations have been performed on graphene in order to tune its band structure10. It is to note that other two dimensional (2D) hexagonal systems i.e. silicene and germanene11 also exhibit linear dispersion relation near Fermi level (EF). Previously, it was the perception that honeycomb lattice is necessary for the existence of Dirac cones. However, modern scientific advances have discarded the above mentioned fact13. Alternatively, Wang et al.14 have critically explored the conditions for the emergence of Dirac cones in 2D lattice. It is to note that the rectangular lattices viz. buckled T-graphene13, 6,6,12-, 14,14,14-, and 14,14,18-graphyne15 also satisfies the condition14. Furthermore, Xu et al.16 have availed structural search method in combination with first-principles calculations to introduce three tetragonal graphene allotropes S-, D- and E-graphene. These allotropes are sp2 hybridized and dynamically stable. Surprisingly, the linear valence and conduction bands in S-graphene touchs each other at two distinct Dirac points in the irreducible Brillouin zone (IBZ). Whereas, D- and E-graphene exhibit only one Dirac point similar to graphene. Therefore, in this work we want to address the key reason behind the occurrence of two Dirac cones in S-graphene. In addition, we are also interested in examining the robustness of the Dirac cones to tune the band structure of S-graphene.The first experimental isolation of graphene17. This phase of materials exhibits the quantized Hall resistance in case of the integer quantum Hall effect (IQHE)19. The IQHE can not be explained in terms of the spontaneous symmetry breaking of Landau theory20. It has been explained with the help of topological band theory. For the purpose, Haldane21 explicitly introduced a scheme to break the time-reversal symmetry giving rise to the anomalous quantum Hall effect (AQHE). The time reversal symmetry can be broken with the help of the staggered magnetic flux in a way that the net magnetic flux in each plaquette is invariably zero. The translational symmetry of the lattice has thus been restored. These systems are better known as topological Chern insulators. It is to note that the Chern insulators exhibit non-zero Hall conductance in the absence of any global magnetic flux22. The topological phase transition connecting two regimes with a distinct Chern numbers (0 to ±1). The Chern number is a topological index that reveal the information about the phase evolution of wavefunctions around the Brillouin zone (BZ) torus. Moreover, remarkable experimental advances in the field of ultracold atoms26 and photonic systems30 have successfully evinced the realization of non-trivial topological phases. One of the key advantages of Haldane model is certainly the experimental accessibility of its phase diagram in case of the non-interacting ultracold systems25. Besides, the lattice dynamics can be efficiently attainable via manipulating any single site31. Furthermore, an extended version of Haldane model32 exhibits that the long range interaction generates additional satellite Dirac points. These Dirac points play a crucial role in explaining the sudden quenching dynamics of the model. The nonequilibrium dynamics of the edge current of the semiopen Haldane model has also been reported33. Moreover, these symmetry protected edge states are extremely important in the study of the superconductors with Majorana Fermions34, spin Hall insulators37, three dimensional topological insulators38 etc. The paper is organized as follows. In the next section (section-II) we have discussed the exact RSRG scheme on S-Graphene like tetragonal lattice. In section-III we have described an analytical description on the emergence of two Dirac cones in the IBZ of the S-graphene. In the subsequent section-IV the robustness of the Dirac cones has been well explored. In addition, we have proposed a method in section-V to obtain the Haldane lattice of S-graphene for describing its topological phase with non-zero Chern number. Finally, the conclusion has been drawn at the end of this paper.The topological insulators are the bulk insulators with conducting surfaceset al.16 as a stable allotrope of graphene called S-graphene. The tetragonal unit cell of S-graphene is defined by the lattice vectors 42 to compute the dispersion (E-k) relation associated with the system through tight binding Hamiltonian. In particular, we have decimated out the preferred subset of atomic sites of the original lattice to achieve a scaled version of it. The scaled lattice, however, carries all the information of the original lattice. We can perform the process several times without losing any generality. The RSRG process has been initiated by evaluating the set of difference equations for the original lattice using Eq. Our primary aim is to address the emergence of two Dirac cones and their robustness associated with the lattice shown in Fig. i-th and the j-th sites. The electron’s hopping is restricted between nearest neighbour (NN) only. It is clear from Fig. Here, F = Now, we want to decimate the red shaded atoms shown in Fig. F. In a similar vein, we have repeated the RSRG scheme for the output lattice of the first RSRG process in a more rigorous manner. In accord with the first RSRG scheme, we have chosen another section as shown in Fig. As a consequence, we are left with a new scaled lattice, depicted in Fig. As an example, we have decimated the atomic sites b and e using the following relationsc and f site also for the corresponding decimation and the renormalized lattice is depicted in Fig. We can use similar relations for t″ present in the system. Such a two-band structure can generically be treated as a two-level system that corresponds to a two-dimensional Hilbert space  have the same value similar to the original lattice. Therefore, the dispersion relation has the formWe now start with the most trivial case, i.e. all the hopping parameters of the original lattice are uniform say, E-k spectra over the entire tetragonal BZ. As already anticipated we have observed the occurrence of two distinct Dirac cones ‘A’ and ‘B’ at specific k-points lying between y is invariably zero. Whereas, ky has a constant value 0.5 near the second Dirac point ‘B’. The dispersion relations between different symmetry points has been described in Table Moreover, we have plotted the dispersion relation to realize the mentclass2pt{minimF. This is a signature of particle hole symmetry in the system. Since, we have only considered the NN hoppings in a two-level system, this symmetry is well expected17. A pictorial representation of all the dispersion relations has been provided in Fig. vF) by expanding the dispersion equations in Taylor series near Dirac points. Neglecting the quadratic and higher order terms of the series we can compare the result with qx = 2πkx/a where, 2, vF = ±6 m/s 43 has previously been reported to be ≈1 × 106 It is worthy to note that the dispersion relations are symmetric about E44. During the computation, the Perdew-Burke-Ernzerhof (PBE) parameters are employed to treat the exchange-correlation part of density functional. Besides, the generalized gradient approximation (GGA) with double In order to support the band structure obtained analytically, we have performed the density functional theory (DFT) computation with the help of SIESTA packaget3 and t″ are distinct. In this case, the dispersion relation is given by Eq. t3 and t″ that allows the band gap opening in the S-graphene system. In this context, we would like to define a dimensionless parameter r that satisfies the relation Now, we want to deal with the more generic case i.e. the hopping parameters of the renormalized lattice z orbital owing to the fact that these orbitals solely contribute in the formation of Dirac cones. The NNTB Hamiltonian in the Wannier basis can thus be expressed as followsNext, we are interested to investigate the robustness of the individual Dirac cone. The underlying objective is obviously to discard the relation i-th to (i + 1)-th site. For the consistency check, we have obtained the band spectra corresponding to the Hamiltonian given in Eq. τ = 1 eV. The system exhibits the existence of two Dirac points under above conditions as depicted in Fig. τ (>t2). It has been observed that the position of the Dirac points move towards the higher symmetry points with decreasing t2. There is a critical value t2 = τ/3, however, can not split the Dirac cones for t3 < τ. This observation is also valid for t3 = 0. It can be argued that both the Dirac points are situated at the BZ path parallel to kx axis. Hence, breaking of the periodicity along the y-axis (i.e. t3 = 0) transforms the sheet into 1D nanoribbon of particular width. This ribbon will also exhibit Dirac cones. In contrary, the condition t3 > τ, induces a band gap in the system above t3 = 2τ. The above criteria is also valid for t4. In addition, we have considered the asymmetrical hopping parameters and obtained that the Dirac point A is robust to the parameter t4 upto the relation t4 = 2t′. Here, we have considered, t1 = t3 = t′ and t, t2 ≥ t′.Here, mentclasspt{minimav ≤ v < 0 protects the Dirac point B. Here, v is the ratio between the non-zero vertical renormalized hopping parameter  ≤ t and t3 ≤ 2t2 removes the degeneracy of A but not B. These results are listed in Table F giving rise to the significant change in their carrier mobility. In order to realize the feasibility of such hopping relations in band gap tuning we have applied stress in the system along x-axis using DFT. We have observed (not shown here) that 1% strain can split the Dirac cones. The result is consistent as the hopping parameter strongly depends on the separation between the neighbouring atoms.Additionally, we have explored two distinct conditions that lift the degeneracy of one Dirac point but other one remain unaltered. The analytical calculation reveals that the condition 0 < entclass1pt{minimaε is connected with the three neighbouring atoms with on-site potential −ε and vice versa. We have observed that even a small anisotropy in the on-site potential can induce band opening in the system as depicted in Fig. Subsequently, the on-site symmetry within the unit cell has been broken, while the hopping parameters remain uniform. Therefore, the atom with on-site energy +t1) only, then the system exhibits semimetallic band structure and the particle-hole symmetry is restored. This unreal particle-hole symmetry can be destroyed in presence of next nearest neighbour (NNN) hopping  of the tetragonal lattice identical to S-graphene. The exact RSRG scheme efficiently reduces the degree of difficulty of the model from eight atoms per unit cell to the two atoms per unit cell. Moreover, the NNTB Hamiltonian of such two-level tetragonal system essentially exhibits two distinct Dirac points in the (IBZ). As an important note, the Fermi velocity of the SG system (


Although there was a low effect size (2 = 0.153) was found between the crossing method and the minima and functional minima methods. This indicates that those methods assess different events during the turn switch phase. In conclusion, the sensors and assessment methodologies compared in this study are not interchangeable with the possible exception of the minima and functional minima assessed with FP.Several methods to determine turn switch points during alpine skiing using the vertical GRF exist in the literature. Although comparative studies between pressure insoles (PI) and force platforms (FP) have been conducted, there are no reports comparing the detected time points. Yet, these sensors and methods have been used interchangeably. This study aims to compare the turn switch time points with both sensors and various methods. Twenty skiers performed turns with FP and PI for two different ski styles (high and low dynamic turns). Three different assessment methodologies were compared: minima, functional minima, and crossings. Bland Altman and repeated measures ANOVA were used to assess statistical differences. Main effects of sensor and method were observed ( In sports, the determination of performance usually depends on small details. Consequently, qualitative assessment of the factors influencing performance is necessary for both recreational and elite levels. The characteristics of alpine skiing make it challenging to study the different features related to performance, injuries, or coaching. Over the last decades there have been several studies using sensors that could collect data while skiing .A total of 20 skiers  took part in the study. Before the measurement, all participants were informed in detail about the testing procedures, as well as possible benefits and risks of the investigation prior to signing the consent form approved by the local Ethics Committee. The experiment was conducted in accordance with the Declaration of Helsinki.The measurements were performed for 10 days within 2 weeks. The snow temperature was consistent across all measurement days with a mean temperature of −1.1 ± 2.2°C. The mean air temperature was −0.4 ± 4.8°C. The upper part of the measurement slope had an inclination of 23° while the bottom part had an inclination of 15°. The slope was machine groomed daily resulting in a compact layer of natural and artificial snow.Two different skiing styles were performed. The skiing technique “Carving in Short Radii”  used recreational skis  and the skiers classified as experts (n = 10) used racing skis . Regardless of the assessed level, all skiers were able to properly perform the required ski styles. The skiers used their own ski boots. The skis were equipped with a portable FP system and a pair of PI were placed inside the liners  mounted under the toe and heel binding of each ski. Each dynamometer weighed 0.9 kg, was 36 mm high, and consisted of a top and bottom plate connected by three three-dimensional piezoelectric force transducers. Amplifiers, power supply, supply box, and data loggers (4 kg) were carried in a backpack worn by the skiers . Prior to the application of the turn detection methodologies, the data sets where synchronized (based on GRF peaks produced by the stomps). The force values of the PI are the sum of the force from each cell, which is obtained multiplying its pressure by its area.The three different turn switch methods assessed were :GRF minima. This method uses the minimum value of the vertical component of the GRF determined by the sum of forces from both legs , low dynamic turns , and for all turns pooled together .Data processing was performed using IkeMaster  and Matlab . To assess the interchangeability and agreement between methodologies and sensors, the bias, and limits of agreement were calculated as proposed by Bland and Altman  . This reference was calculated independently for each turn and cut-off frequency as the mean of the 6 measured turn switch points  and partial eta squared   was used to assess statistical differences with respect to system (FP vs. PI), calculation method , filter (1 vs. 3 vs. 6 Hz), and ski dynamics (high vs. low dynamic turns). Mauchly's Test of Sphericity indicated that the assumption of sphericity was not met, consequently Greenhouse-Geisser correction was utilized. If significant differences were found, Bonferroni's The agreement between sensors and methodologies are presented in The comparison between FP and PI for all turns pooled together yielded bias lower than 0.05 s and ranges between 1.09 and 1.36 s, except for the “crossing” method with ranges starting at 0.58 s. The “minima” and “functional minima” methods had the highest agreement for both sensor types (FP and PI). Although the comparison between “minima” and “functional minima” methods had the highest agreement for both sensors, the results were not similar. Including all cut-off frequencies, the bias and range were <0.002 and 0.400 s for the FP, but >0.012 and 0.850 s for the PI, respectively. This behavior was consistent, the comparison between assessment methodologies showed systematically lower bias and range values when the FP system was used.p < 0.001), but the effect size was small (p < 0.001) with a large effect size . On the other hand, the differences between both the minima and the functional minima and the crossing method were >0.13 s with a large effect size (η2 = 0.153).Results for the mean and standard deviation for each assessment option are shown in The average turn duration for high and low dynamic turns was 1.66 ± 0.27 and 2.55 ± 0.32 s, respectively. The range between FP and PI for the most similar methodologies  represents ~30 and 40% of turn duration for high and low dynamic turns, respectively. The range between minima and functional minima assessed using the PI represents a 33 and 48% of the turn duration for high and low dynamic turns, respectively, and 13% of the turn duration when assessed with the FP, independent of the turn dynamics.The current study focused on the comparison between time points of the turn switch during alpine skiing assessed with different methodologies and using FP and PI. The results showed that all the methods yielded better agreement when the data was collected using the FP than when it was collected using the PI . This trn = 2,472) lead to a type 1 error, were negligible differences are deemed statistically significant. Regardless of the risk of type 1 error, and to the potential misinterpretation of the data, the magnitude of the ranges yielded by the Bland and Altman comparisons show a CI that represents between 30 and 40% of the total turn duration. Consequently, due to the lack of agreement between sensors, these sensors should not be interchanged when comparing turn switch points or metrics measured turn by turn as the cutting point will affect the calculations . A possible interpretation of those results is that the large number of turns included in the analysis (2 > 0.153) and not between the minima and functional minima . Nevertheless, the ranges between minima and functional minima assessed with PI represents >30% of the turn duration which leads to the conclusion that they are not interchangeable. On the other hand, when using the FP, the range represents a 13% of the turn duration, which depending on the aim of the turn detection, could allow for the use of both the minima and functional minima methods interchangeably from FP measurements.The same discussion is relevant for the comparison between the methods. Although there is a main effect of methodology, with a large effect size (0.427), the differences are mostly with respect to the crossings method  highlight the differences of the points actually detected. Unfortunately, we cannot determine which sensor or method would be most representative of the true turn switch point due to the lack of valid reference data, both in the literature and this study. Based on the results, the methodology based on the minima seems to be the most appropriate to apply in the field. It presents the lowest bias values between the two sensors and also the smallest range for highly dynamic turns. On the other hand, both sensors present some advantages and disadvantages. FP showed consistently better results, yet the use of FP in training is not a feasible option. It changes the height of the bindings, adds weight to the skis and implies more weight and wires in the skier's body. For this reason, the implementation of a less cumbersome pressure sensor outside of the boot could potentially solve the problem of the missing forces through the boot cuff and provide reliable data similar to the FP. A future study using a gold standard methodology for the location of the turn switch point needs to be defined and consequently compared with the various methodologies applied for detecting the turn switch.The aim of the study was to assess if sensors (FP and PI) or assessment methods  could be used interchangeably, and according to the results of this study, they are not. The only exception being the minima and functional minima methods assessed with FP. The results of the study also suggest that the use of the FP sensor to determine turn switches based on GRF is recommended. Further research is needed to evaluate the precision of the different systems and determine which assessment method is most correlated with the real turn switch point.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of the University of Salzburg. The patients/participants provided their written informed consent to participate in this study.AM and TS: conceptualization and formal analysis. AM, KN, PS, and TS: methodology. AM: software and visualization. AM, CS, and TS: investigation. TS: resources, supervision, and funding acquisition. PS: data curation. AM: writing—original draft preparation. TS, CS, PS, and KN: writing—review and editing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Pleurotus ostreatus is presented as a case study, and its potential role in regulating the ligninolytic system, secondary metabolism, development, and fruiting body initiation are discussed. We propose that deciphering the nature of effector-like SSPs will contribute to our understanding of development and communication in saprophytic fungi, as well as help, to elucidate the origin, regulation, and mechanisms of fungal-host, fungal-fungal, and fungal-bacterial interactions.Small secreted proteins (SSPs) comprise 40–60% of the total fungal secretome and are present in fungi of all phylogenetic groups, representing the entire spectrum of lifestyles. They are characteristically shorter than 300 amino acids in length and have a signal peptide. The majority of SSPs are coded by orphan genes, which lack known domains or similarities to known protein sequences. Effectors are a group of SSPs that have been investigated extensively in fungi that interact with living hosts, either pathogens or mutualistic systems. They are involved in suppressing the host defense response and altering its physiology. Here, we aim to delineate some of the potential roles of SSPs in saprotrophic fungi, that have been bioinformatically predicted as effectors, and termed in this mini-review as “effector-like” proteins. The effector-like Ssp1 from the white-rot fungus  The success of fungi to adapt and proliferate in diverse ecological niches is dependent on their ability to respond to changes in the environment. The rich, yet versatile, fungal secretome is an important component that facilitates the fast adjustment to changes occurring in the vicinity of the growing and developing fungus . The sizSSPs are secreted by fungi independently of their lifestyle and are defined as proteins that contain a signal peptide and a sequence of less than 300 amino acids. Many SSPs are coded by orphan genes, lacking known PFAM domains or similarities to known sequences. The proportion of SSPs ranges from 40 to 60% of the secretome across all lifestyles and phylogenetic groups within the fungal kingdom . SSPs haHere, we follow the common paradigm defining effectors as SSPs used by a range of pathogenic and beneficial fungi to alter the physiological status of the host plant . We specSSPs functioning as effectors are common in several plant pathogens . Many efDuddingtonia flagrans, 117 effectors were predicted, of which PefB was induced during interaction with the host and was imported into host nuclei in vitro  . The besoot tips . It is snization . MiSSP8 ormation .Rhizophagus irregularis SP7 protein, manipulates the ethylene-signaling pathway and is localized to the host nucleus where it subsequently reshuffles plant defense pathways  or by overexpression of the dominant Ssp1 member (OEssp1)  . Analysitabolism , along wtabolism . Overexptabolism , which itabolism . Howevertabolism .SSPs are a significant, yet still a functionally-elusive, part of the fungal secretome, especially in saprophytes. Nonetheless, some of them are the likely ancestors of the better understood effectors in pathogenic and mutualistic fungi . Part ofP. ostreatus highly resemble the mentioned characteristics of QS , but can be carried out in a growing array of SSP-producing fungi, such an Armillaria ostoyae, Schizophyllum commune, and more , imposing technical difficulties when it comes to their genetic manipulation. In order to uncover and validate their role(s) and function(s), the research must be accompanied by a “wet bench” experimental approach. Perhaps some of these can be achieved by using RNAi and/or CRISPR-Cas9 technologies  interactions.DF, OY, and YH wrote this mini-review together.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.This meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients.Published articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI).2 = 33%). High sPD-L1 had worse PFS , and worse DFS , without significant statistical difference in RFS .A total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59–2.15, IHigh sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future. Immune checkpoint inhibitors such as anti-PD-1/PD-L1 have remarkable clinical benefits in a variety of tumors . The expPD-L1 exists in two forms; membrane-bound and soluble form . StudiesStudies on the relationship between sPD-L1 and the prognosis of cancer patients have yielded contrasting results. In NSCLC, studies by He et al. showed that patients with high sPD-L1 have a reduced risk of death . HoweverRelevant articles published in various databases were searched since the inception of the databases to September 2020. The Pubmed, EMBASE, and Cochrane clinical trial databases were searched for the meta-analysis. The Clinicaltrial.gov, American Society of Clinical Oncology (ASCO) and ESMO databases were also searched. Search terms were composed of various combinations of “soluble PD-L1”, “sPD-L1”, “serum PD-L1”, “plasma PD-L1”, “circulatory PD-L1”, “blood PD-L1”, “programmed death ligand 1”, “B7-H1” and “cancer”, “neoplasm”, “carcinoma”, “lymphoma”, “sarcomas”. The language of the article was not restricted.The inclusion criteria for various studies were: i. The included patients were all pathologically diagnosed tumor patients; ii. With analyzable soluble PD-L1 data; iii. With sufficient clinical features and data that could be combined to analyze soluble PD- L1 and survival prognosis; iv. Had their sPD-L1 levels detected by enzyme-linked immunosorbent assay (ELISA). The exclusion criteria were: i. Case reports, reviews, and tissue immunohistochemical (IHC) detection for PD-L1; ii. Animal experiments; iii. No direct analysis of the relationship between soluble PD-L1 and survival prognosis; iv. Incomplete data or non-original research.First, the outcomes of each study were extracted, including overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) prognosis data. Next, the baseline data of the studies were extracted and analyzed; publication years, study type, patient characteristics, treatment methods, and the cut-off value of sPD-L1, etc. Based on the purpose of our research, OS was the primary outcome of interest. All data screening and extraction processes were independently performed by two investigators.The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the study. The NOS consists of three parts: selection (4 points), comparability (2 points), and outcome evaluation (3 points). 2 statistics. I2 >75% indicated considerable heterogeneity  of all results was calculated. All outcomes were directly extracted from the studies. Time-to-event endpoints  were pooled with the use of hazard ratio (HR). Heterogeneity was assessed using the χ2-based Q test and Iogeneity . The ranWe initially identified 926 articles from the searched databases, and after excluding duplicates, 642 articles remained. After excluding 514 records, the full text of 128 articles were screened. After full-text screening, 97 studies were excluded due to the following reasons; not original studies n = 11), irrelevant studies n = 24), irrelevant outcomes n = 32), incomplete data n = 17), and the cohort overlaps n = 13). Finally, 31 studies involving 17 tumors and a total of 3,780 patients met our inclusion criteria Figure 1, irrelev. Finally, and the, irrelev, incomplThe main characteristics of the 31 studies are summarized in 2 = 33%)  Figure 22 = 83%). Besides, six studies included DFS data. High sPD-L1 was correlated with worse DFS . Moreover, only two studies reported RFS, and sPDL1 was insignificantly correlated with a worse RFS   Table 2.2 = 21%) and prospective studies  was correlated with worse OS. Studies were stratified according to whether surgery was performed, and the results showed that surgery did not affect the correlation between sPD-L1 and OS   Table 3.2 = 45%) and multivariate analysis  . We also performed subgroup analyses based on cut-off points . We found that the significant association between sPD-L1 and survival did not change with the change in cutoff points. Furthermore, sPD-L1 was associated with worse OS in both univariate  Table 3.This meta-analysis summarizes the correlation between the level of sPD-L1 and the prognosis of various cancer patients. The main significance of sPD-L1 detection is to establish a minimally invasive, easy-to-clinical, and predictive immune biomarker for cancer patients.PD-L1 can be divided into membrane-bound PD-L1 (mPD-L1) and sPD-L1. It is believed that sPD-L1 is mainly produced by the proteolysis of mPD-L1. The immunosuppressive correlation and prognostic values of mPD-L1/sPD-L1 have not been established. Currently, IHC detection is commonly used in clinical practice to detect mPD-L1. Previous studies have explored the relationships between mPD-L1 expression levels in tumor tissues and clinical prognosis. However, these studies are limited by difficulties in sampling tumor tissues, as well as by the inability to dynamically detect changes in patients during treatment. In addition, the relationships between the levels of PD-L1 as detected by tissue IHC and the prognosis of cancer patients are not clinically binding , 43. UncWe found that high sPD-L1 levels can be used as a prognostic biomarkers for poor treatment outcomes. Secondly, it has been proved that the sPD-L1 still retains its biological activity. We can further postulate that sPD-L1 in peripheral blood can be able to specifically bind T cells in peripheral blood, thereby, inhibiting T cell activity and inducing systemic immune suppression . When PDSubgroup analyses were performed based on the treatment or cut-off value of the patient. In the subgroup analysis of patients receiving immunotherapy, patients with high sPD-L1 levels were correlated with a worse OS. An NSCLC study showed that the death risk in patients with high levels of sPD-L1 was 2.68 (95%CI 1.36–5.28) times the risk in patients with low sPD-L1 levels . Given tsPD-L1 can be used as a good indicator for the survival of cancer patients. Several studies have evaluated the predictive role of other immune-related biomarkers  in different types of cancers . Meyo etTwo systematic reviews and meta-analysis have evaluated the relationship between sPD-L1 and tumor prognosis. The review by Ding et al. in 2017 included eight articles with a total of 1,102 cancer patients . Wei et This study has certain limitations. First, the studies included in this meta-analysis were observational studies, due to the lack of relevant randomized controlled trials (RCTs). Higher quality RCTs are needed to further evaluate the prognostic value of sPD-L1. Second, the number of patients with each tumor included in this study was small, and a larger sample population is needed for verification. Third, different tumor types have different molecular signatures including immune checkpoint regulators, therefore, combining them leads to inaccurate inferences and misleading clinical applications. Finally, the cut-off values of sPD-L1 in different studies were significantly different, leading to limitations in clinical applications. In future, more studies should aim at accurately establishing the correlation between sPD-L1 expression level and prognosis. However, this study shows the prognostic value of sPD-L1 in a variety of tumors and immunotherapy, indicating that sPD-L1 can potentially serve as an innovative biomarker for predicting the prognosis of cancer patients.In conclusion, this meta-analysis revealed that high sPD-L1 levels were associated with worse survival outcomes  in cancer patients. And among patients who had received immunotherapy, patients with high sPD-L1 levels had worse OS. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.PH, HL: protocol/project development. PH, HL, YW: data collection and management. HL, WH: data analysis. HL, WH, YZ: manuscript writing/editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Graphene-polymer nanocomposites continue to gain interest in diverse scientific and technological fields. Graphene-based nanomaterials present the advantages of other carbon nanofillers, like electrical and thermal conductivity, while having significantly lower production costs when compared to materials such as carbon nanotubes, for instance. In addition, in the oxidized forms of graphene, the large specific area combined with a large quantity of functionalizable chemical groups available for physical and/or chemical interaction with polymers, allow for good dispersion and tunable binding with the surrounding matrix. Other features are noteworthy in graphene-based nanomaterials, like their generally good biocompatibility and the ability to absorb NIR radiation, allowing for the use in biomedical applications, such as drug delivery and photothermal therapy.This Special Issue provides an encompassing view on the state of the art of graphene-polymer composites, showing how current research is dealing with new and exciting challenges. The published papers cover topics ranging from novel production methods and insights on mechanisms of mechanical reinforcement of composites, to applications as diverse as automotive and aeronautics, cancer treatment, anticorrosive coatings, thermally conductive fabrics and foams, and oil-adsorbent aerogels. The most impactful works are summarized in this editorial.−8 (aPa nm−1), 9.75 × 10−10 (nm), 2.1 × 10−10 (N nm−1), respectively, followed by an exponential regressive law with the exponent, α = 7.74. It was shown that the commonly assumed bilinear softening law of the cohesive interface could lead up to a 55% error in the predicted separation of the interface [Taking advantage of graphene’s unique mechanical properties, Irez et al. newly designed lightweight and cost-efficient composite materials for the aeronautic industry using recycled fresh scrap rubber, epoxy resin, and graphene nanoplatelets (GnPs). After manufacturing the composites, their bending strength and fracture characteristics were investigated by three-point bending (3PB) tests. Halpin–Tsai homogenization adapted to composites containing GnPs was used to estimate the moduli of the composites, and satisfactory agreement with the 3PB test results was observed. In addition, 3PB tests were simulated by the finite element method incorporating the Halpin–Tsai homogenization, and the resulting stress–strain curves were compared with the experimental results. Mechanical test results showed that the reinforcement with GnPs generally increased the modulus of elasticity as well as the fracture toughness of these novel composites. The typical toughening mechanisms observed were crack deflection and cavity formation. Considering the advantageous effects of GnPs on these novel composites and the cost efficiency gained by the use of recycled rubber, these composites have the potential to be used to manufacture various components in the automotive and aeronautic industries as well as smart building materials in civil engineering applications . The mecgT of 105.2 °C, which were 159%, 191%, and 49.4% higher than those of the unreinforced UPR/TO resin, respectively. Compared to neat UPR, the biobased UPR nanocomposite with 0.10 wt.% of GO even demonstrated superior comprehensive properties . Therefore, the developed biobased UPR nanocomposites are very promising to be applied in structural plastics [Using a different resin, Liu et al. prepared graphene-reinforced tung oil (TO)-based unsaturated polyester nanocomposites via in situ melt polycondensation integrated with Diels–Alder addition. Functionalized graphene sheets derived from graphene oxide (GO) were then extracted from the obtained nanocomposites and carefully characterized. The mechanical and thermal properties of the TO-based unsaturated polyester resin (UPR) were greatly improved by the incorporation of GO. At the optimal GO content (0.10 wt.%) the nanocomposite showed a tensile strength and a tensile modulus of 43.2 MPa and 2.62 GPa, and Functional fabrics have gained attention as an environmentally-friendly synthesis route. Yang et al. developed novel bamboo pulp fabrics with thermal conductivity properties by coating the fabric with graphene and cellulose nanocrystal (G/CNC) solutions. The influences of G and CNC concentrations on the properties of fabrics were studied. It was found that the viscosities of the G/CNC solutions increased with an increase of G contents. G had an obvious thickening effect. Furthermore, compounded fabrics with different G and CNC contents (GCBPFs) were prepared and extensively characterized in terms of their thermal and mechanical properties as well as morphology. The ultimate thermal conductivity, bursting strength, and tensile strength of the GCBPF were 0.136 W/m K, 1.514 MPa, and 25.8 MPa, with 4 wt.% CNC and 3 wt.% G contents. The results demonstrated that the as-fabricated GCBPFs with favorable thermal conductivity could be applied as a novel fast cooling textile for the clothing industry [3), high porosity (98.8 %), good hydrophobicity (water contact angle of 142°), and great adsorption capacity (oil absorption reaching 96 times its own weight). More importantly, the oriented aerogel had high strength, whose compressive stress at 80% strain reached 0.22 MPa, and could bear more than 22 times its own weight without deformation. Therefore, a CNF/PVA/GO composite aerogel could be prepared by a simple and easy-to-operate directional freeze-drying method, being a promising absorbent for oil-water separation [Under the current situation of frequent oil spills, the development of green and recyclable high-efficiency oil-absorbing aerogel materials has attracted wide attention from researchers. Zhou et al. reported a high-strength, three-dimensional hydrophobic cellulose nanofiber (CNF)/polyvinyl alcohol (PVA)/graphene oxide (GO) composite aerogel with an anisotropic porous structure, which was fabricated by directional freeze-drying technology using anisotropically grown ice crystals as a template, followed by hydrophobic treatment with a simple dip-coating process. The prepared composite aerogel presented anisotropic multi-level pore microstructures, low density 17.95 mg/cm mg/cm3, Besides the graphene-based materials intrinsic properties and the interactions with the polymer matrix, the amounts of filler used and the composite production methods can have an impact on its final properties. Huang et al. studied the effects of increasing graphene nanosheet (GNS) concentrations on variations in the structure and properties of electrospun GNS-filled poly (PTT/GNS) composite fibers, such as in its morphology, crystallization behavior, mechanical properties, and electrical conductivity. The effects of GNS addition on solution rheology and conductivity were also investigated. GNSs were embedded in the fibers and formed protrusions. The PTT cold crystallization rate of PTT/GNS composite fibers increased with the gradual addition of GNSs. A PTT mesomorphic phase was formed during electrospinning, and GNS could induce the PTT mesomorphic phase significantly during PTT/GNS composite fiber electrospinning. The PTT/GNS composite fiber mats (CFMs) became ductile with the addition of GNS. The elastic recoveries of the PTT/GNS CFMs with 170 °C annealing were better than those of the as-spun PTT/GNS CFMs. Percolation scaling laws were applied to the magnitude of conductivity to reveal the percolation network of electrospun PTT/GNS CFMs. The electrical conductivity mechanism of the PTT/GNS CFMs differed from that of PTT/GNS composite films. Results showed that the porous structure of the PTT CFMs influenced the performance of the mats in terms of electrical conductivity . HendrixGraphene impermeability against water, oxygen, and ions diffusion, together with its large surface area, make it an outstanding material for application in anticorrosion surface coatings. Lei et al. studied the corrosion behavior of zinc-rich epoxy primers or paints (ZRPs) with different conducting polyaniline-grafted graphene (PANI/Gr) contents. The conductivity of the formed PANI/Gr nanosheets was significantly improved by employing Gr as the inner template to synthesize the PANI. The protective properties and the electrochemical behavior of coatings with artificial defects were investigated by monitoring the free corrosion potential versus time and by using localized electrochemical impedance spectroscopy (LEIS). A synergetic enhancement of the physical barrier role of the coating and the zinc sacrificial cathodic protection was achieved in the case of ZRP including PANI/Gr nanosheets. In addition, the ZRP mixed with the PANI/Gr at a content of 0.6% exhibited the best anticorrosion performance across the range of investigated PANI/Gr contents .2. Thermogravimetric analysis allowed for estimating the amount of PEG in rGOn-PEG to be of about 56.1%. Simultaneous reduction and PEGylation increased the lateral dimensions from 287 ± 139 nm to 521 ± 397 nm, as observed by transmission electron microscopy and dynamic light scattering. It was found that rGOn-PEG exhibited roughly 13-fold higher absorbance in the near-infrared radiation (NIR) region, as compared to unmodified GOn. Low power (150 mW cm−2) NIR irradiation using LEDs resulted in rGOn-PEG heating up to 47 °C, which is within the mild PTT temperature range. PEGylation strongly enhanced the dispersibility of rGOn in physiological media  and also improved the biocompatibility of rGOn-PEG, in comparison to GOn (25–250 μg mL−1). After a single NIR LED irradiation treatment of 30 min, a decrease of ≈38% in A-431 cells viability was observed for rGOn-PEG (250 μg mL−1). Together, these results demonstrate the potential of irradiating rGOn-PEG using lower energy, cheaper, smaller, and safer LEDs as an alternative to high-power lasers for NIR mild hyperthermia therapy of cancer, namely nonmelanoma skin cancer [Graphene and graphene polymer composites have been widely explored for the development of medical implants, antibacterial materials, biosensors, drug and gene delivery systems, as well as phototherapy platforms. Gurunathan et al. produced graphene oxide–green platinum nanoparticles (GO-PtNPs) using vanillin and studied its effect on human prostate cancer cells (LNCaP). GO-PtNP cytotoxicity in LNCaP cells was demonstrated by measuring cell viability and proliferation. Both decreased in a dose-dependent manner compared to that by GO or PtNPs alone. GO-PtNP cytotoxicity was confirmed by increased lactate dehydrogenase release and membrane integrity loss. Oxidative stress induced by GO-PtNPs increased malondialdehyde, nitric oxide, and protein carbonyl contents. The effective reactive oxygen species generation impaired the cellular redox balance and eventually impaired mitochondria by decreasing the membrane potential and ATP level. The cytotoxicity to LNCaP cells was correlated with increased expression of proapoptotic genes  and decreased levels of antiapoptotic genes (Bcl2 and Bcl-xl). Activation of the key regulators p53 and p21 inhibited the cyclin-dependent kinases Cdk2 and Cdk4, suggesting that p53 and p21 activation in GO-PtNP-treated cells caused genotoxic stress and apoptosis. The increased expression of genes involved in cell cycle arrest and DNA damage and repair as well as the increased levels of 8-oxo-deoxyguanosine and 8-oxoguanine suggested that GO-PtNPs potentially induce oxidative damage to DNA. Thus, GO-PtNPs are both cytotoxic and genotoxic. LNCaP cells appear to be more susceptible to GO-PtNPs than to GO or PtNPs. Thus, GO-PtNPs have potential as an alternate and effective cancer therapeutic agent. In other words, this work shows that the combination of graphene oxide with platinum nanoparticles opens up new perspectives in cancer therapy. However, further detailed mechanistic studies are required to elucidate the molecular mechanism of GO-PtNPs induced cytotoxicity in prostate cancer [n cancer .


Rather than a single disease entity, sarcoidosis may be a constellation of “sarcoidoses” with a characteristic pattern of organ involvement and clinic course, depending upon the triggering exposure and underlying epidemiologic factors such as race. This review examines the racial disparities inherent to sarcoidosis disease course and mortality and discusses factors that may be responsible for these findings. In the United States, black patients with sarcoidosis experience more severe pulmonary disease, more multiorgan involvement, and an overall worse prognosis with higher rates of hospitalization and mortality. Beyond inherent genotype, ascertainment and access to medical care, physician implicit bias, and patient perceived discrimination likely play a role. Moving forward, epidemiologic concepts can be used to formulate strategies for control, treatment, and even prevention of disease in black Americans at risk for developing life-altering or life-threatening sarcoidosis phenotypes. Identification and rectification of modifiable risk factors such as socioeconomic status, lack of insurance, and financial barriers to care as well as the incorporation of implicit bias training for physician will likely lead to improvement in discordant outcomes. Sarcoidosis is a multisystem disease characterized by granulomatous inflammation. Although its etiology remains unknown, sarcoidosis is believed to represent a genetically primed abnormal immune response to an antigenic exposure . Rather In the United States, in particular, different phenotypic expressions are found between black and white subjects, likely resulting from genetics, environment, socioeconomics, implicit or racial biases, or a combination thereof. Given the current political climate and impetus for change in the United States, it is important to shed light on discordant clinical outcomes in vulnerable patient populations. This article examines the racial disparities inherent to sarcoidosis disease course and mortality and discusses factors that may be responsible for these findings.Consistently, black subjects are reported to be most affected by sarcoidosis, black females even more so. Studies reporting incidence and prevalence of sarcoidosis, broken down by race and sex if available, are presented in Dating back to the 1960's, researcher Andrew Z. Keller reported significantly different frequency distributions of sarcoidosis with black patients being more commonly diagnosed and treated than whites . In the In summary, sarcoidosis incidence and prevalence vary greatly based on race with a strong predilection for black populations in the United States, which may be the result of race-specific genetic associations and environmental socioeconomic factors.As stated previously, sarcoidosis likely results from an environmental insult in a genetically susceptible host. The high incidence and prevalence of sarcoidosis in black subjects suggests an inherent genetic susceptibility. In fact, first-degree relatives of black sarcoidosis cases have about a 3-fold disease risk increase .*0602, was shown to confer both increased susceptibility to sarcoidosis and a predilection for radiographic progression of disease in a family-based genetic association analysis of sarcoidosis in U.S. black families (Multiple sarcoidosis susceptibility loci have been explored in candidate gene and genome-wide association studies. These include the highly polymorphic human leukocyte antigen (HLA) genes, residing in the class II major histocompatibility complex (MHC) on chromosome 6, as well as other genes that influence antigen processing and presentation, T-cell activation and recruitment, and granulomatous inflammation at the core of sarcoidosis immunopathogenesis. A particular HLA allele, DQB1families . Conversfamilies . Amongstfamilies . Subsequfamilies . Furtherfamilies .In all, given the identification of multiple candidate genes and suggestive regions for linkage, it is likely that more than one gene influences sarcoidosis susceptibility and disease presentation in black populations. This is further confounded by ancestral differences in admixed black communities residing in the United States.In sarcoidosis the granulomatous inflammation can affect virtually all organs and tissues. However, disease presentation, including extent and severity of disease, has been shown to vary based on demographic variables such as race. A Case-Control Etiologic Study of Sarcoidosis (ACCESS)—a prospective, multicenter study of sarcoidosis patients enrolled within 6 months of diagnosis—provided an opportunity to examine the association of demographic measures, socioeconomic status and barriers to care with severity of disease at presentation, as defined by extent of organ involvement, chest radiographic staging and basic spirometry , 21.As far as organ involvement at presentation, ACCESS showed that black patients tend to experience more extrapulmonary sarcoidosis, affecting the skin (other than erythema nodosum), bone marrow, liver, extrathoracic lymph nodes and eyes . CalciumTherefore, in addition to a suspected genetic predisposition for more severe pulmonary and extrapulmonary disease, the association of black race with socioeconomic status  and severity of disease at presentation suggests that black patients are more likely to have financial barriers to care and resultant delay in seeking care than their white counterparts . AdditioWhile sarcoidosis tends to improve or remain stable in the majority of patients, longitudinal studies have shown worse outcomes are associated with black race and/or lower annual family income , 27. In Furthermore, black patients tend to have a higher rate of hospitalization for sarcoidosis. An analysis of the National Hospital Discharge Survey (NHDS) from 1979 to 2000 showed that mean rates of hospitalization were nine time higher for black patients . A retroAs such, black patients with sarcoidosis experience worse prognosis, more multiorgan involvement, and a higher rate of hospitalization. Beyond inherent genotype, ascertainment and access to preventative and primary care may also be playing a role in this disparity of outcomes for black individuals, as is implicit bias.Many patients with sarcoidosis have a benign clinical course, but for some, it is a chronic, life-altering, and even fatal disease. While overall mortality rates from sarcoidosis have been shown to be increasing, significant differences exist based on race. Data from the National Center for Health Statistics (NCHS), demonstrated a 3% average yearly increase in mortality rate for all-comers with sarcoidosis from 1988 to 2007 . HoweverThis race-specific trend of higher mortality from sarcoidosis at a younger age in black patients has multiple potential explanations, some more alarming than others. Hypotheses include increased incidence and severity of disease, a predilection for the lethal complications of pulmonary fibrosis and pulmonary hypertension, as well as long-standing systemic health and social inequities.As the Covid-19 pandemic has so powerfully illustrated, race plays a significant role as a determinant of health in the United States . Beyond Despite its nineteenth century origin and more than 100 years of inquiry, much about sarcoidosis is still unknown. Perhaps this is because of its many points of divergence—its variant epidemiology, varied triggering exposures and ultimately variable clinical phenotypes or “sarcoidoses.” Regardless, its higher contraction and death rates in black Americans deserves further attention.Ideally, future studies performed will improve our understating of the relationships among exposure, race and other epidemiologic factors, with current clinical phenotypes and outcomes. Such endeavors should include large, matched epidemiologic studies conducted in racially diverse populations, facilitated by large population data sets and disease registries. In addition to facilitating etiologic hypotheses of the exposure-host interaction at the core of sarcoidosis pathophysiology, epidemiologic concepts should be used to formulate strategies for control, treatment, and even prevention of disease in Black Americans who are at the greatest risk for developing life-altering or life-threatening disease. Identification and rectification of modifiable risk factors such as socioeconomic status, lack of insurance, and financial barriers to care will likely lead to improved outcomes. Making anti-racism or implicit bias training an essential professional competency would equip physicians with the tools needed to address racism and its adverse health effects .only when health equity is achieved (Finally, these findings should influence research in the areas of health disparities and disease processes among various racial groups and between the sexes throughout the world. Achieving health equity requires valuing all individuals and populations equally, recognizing and rectifying historical injustices, and providing resources according to need. Health disparities will be eliminated achieved .KH contributed a race-centered review of sarcoidosis epidemiology, highlighting racial disparities inherent to sarcoidosis disease course and mortality and discusses factors that may be responsible for these findings. She was the sole contributing author for this section.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.