All these approaches have shown performance improvement of photodetectors for self-powering applications. A comprehensive analysis encompassing 2D material characterization, theoretical and numerical modelling, device physics, fabrication and characterization of photodetectors with graphene/MoS2 and graphene/h-BN/MoS2 heterostructures with plasmonic effect is presented with potential leads to new research opportunities.A photodetector converts optical signals to detectable electrical signals. Lately, self-powered photodetectors have been widely studied because of their advantages in device miniaturization and low power consumption, which make them preferable in various applications, especially those related to green technology and flexible electronics. Since self-powered photodetectors do not have an external power supply at zero bias, it is important to ensure that the built-in potential in the device produces a sufficiently thick depletion region that efficiently sweeps the carriers across the junction, resulting in detectable electrical signals even at very low-optical power signals. Therefore, two-dimensional (2D) materials are explored as an alternative to silicon-based active regions in the photodetector. In addition, plasmonic effects coupled with self-powered photodetectors will further enhance light absorption and scattering, which contribute to the improvement of the device’s photocurrent generation. Hence, this review focuses on the employment of 2D materials such as graphene and molybdenum disulfide (MoS Light detection mechanism was introduced back in 1887 when Heinrich Hertz discovered that electrodes generate electric sparks when illuminated with ultraviolet light. This was supported with Max Planck’s suggestion that energy carried by electromagnetic fields can be quantized as discrete packets, known as photons or quanta, while studying black-body radiation in 1900. Further enlightenment was made possible with Albert Einstein’s explanation of the photoelectric effect with the support of experimental results. The commercial product of photon detection is the photomultiplier tube (PMT), which was invented in the RCA laboratories in 1930. The limitation of PMTs in terms of high sensitivity towards the magnetic field, high cost, and a complicated mechanical structure opened the opportunity for development of new photodetectors, especially devices that employ semiconductor materials.A device that detects light from the electromagnetic wave spectrum between ultraviolet 0.25–0.4 µm), visible (0.45–0.8 µm) and near infrared 0.9–1.7 µm) and converts it to measurable electrical signals in terms of current, voltage or resistance is known as a photodetector [.7 µm and5–0.4 µm,Although photodetectors with external power supply mode have better performance compared to non-biased photodetectors, this increases the size of the device, making it bulky and inconvenient to be packaged. Moreover, the larger device size limits its applications in many fields, especially for remote sensing and wireless applications. Therefore, self-powering photodetectors that utilize the photovoltaic effect have become preferable and have been intensively studied till now. Self-powering photodetectors have many advantages such as small size, light weight, low cost, low power consumption, high photoresponsivity, fast response and most importantly it works independently without an external power supply and relies on the built-in potential, which contributes to energy savings ,4,7. HowIn general, there are several types of device configurations for self-powered photodetectors, which are the P–N junction type, Schottky junction type and photoelectrochemical (PEC) type ,4,7,8. TThe P–N junction type self-powered photodetector has more advantages compared to other types of photodetectors due to its simple structure, low dark current, high sensitivity, high stability and fast response time. Although the homojunction P–N photodetector achieved great progress in the past, it has performance limitations in terms of weak absorption of photons due to the limited material bandgap energy, especially in self-powering photodetectors. This limitation can be resolved in the heterojunction P–N photodetector, which has two or more materials with different bandgaps that promotes light absorption. Nevertheless, designing heterostructures is challenging, as it is a trade-off parameter towards the performance of the photodetector because recombination may occur at the heterostructure interface. The Schottky junction type has better response speed and higher sensitivity and relies on the presence of a built-in potential, which is in contrast with the ohmic contact photodetector, although it has a large photoconductive gain and higher responsivity. Schottky junction photodetectors can be classified into semiconductor–metal Schottky junction and semiconductor–graphene Schottky junction. The latter has demonstrated outstanding performance, and further enhancement was achievable through interface engineering. PEC is known as a new type of self-powering photodetector with a simpler manufacturing process and larger photoresponsivity but is limited by the stability of the device ,4.2, WS2 and WSe2.The venture of employing 2D materials began back in 2004 when graphene was introduced by Geim and colleagues. Ever since then, there have been many emerging 2D materials that were employed specially for photodetection applications ranging from graphene, transition metal dichalcogenides (TMDs), 2D perovskites, 2D metal–organic frameworks (MOFs) and covalent organic frameworks (COFs), and graphdiynes. Graphene is well known for its unique electrical and optical properties and is still actively utilized in photodetectors. Since the gapless nature of graphene limits its optical performances in photodetectors, it is now being hybridized with other semiconducting materials, especially from the family of 2D materials, and acts as the charge transport layer in the device. In the context of TMDs, there are many famously explored materials such as MoS2 as a large area flexible photodetector with photoresponse of approximately 20 mA/W with response time of a few seconds [The performances of photodetectors determine their relevance of applications in various fields. The improved photoresponse of 2D material-based photodetectors makes them useful for application in areas such as military and civil areas , digital seconds .2-based photodetectors have demonstrated a lower performance compared to other counterparts, a significant improvement in terms of photoresponsivity was shown when MoS2 was hybridized with graphene. Adding to this, further improvements were shown by inserting the hexagonal boron nitride (h-BN) in forming the metal–insulator–semiconductor (MIS) structures, which contributed significantly in terms of lowering the dark current in photodetectors. To the best of the authors’ knowledge, the study on optical devices that employ graphene/h-BN/MoS2 heterostructures was developed in 2015 [on/Ioff ratios where the breakthrough highlight of restoring the photovoltaic effect with van der Waals heterojunctions for self-powered photodetectors was discovered in 2019. The h-BN insertion between graphene and MoS2 showed three orders of improvement in photocurrent and specific detectivity of 6.7 × 1010 Jones with external quantum efficiency of over 80% at zero bias. Since the graphene/h-BN/MoS2 heterostructures have potential in self-powering photodetectors, further studies must be continued to tailor the device structures and modify the behavior of these materials for optimal performance, which is crucial for self-powered photodetectors because these advanced devices are expected to detect the smallest light signal without relying on external biasing. Therefore, it is important to comprehend and summarize the device physics, fabrication process, working principles and advances based on previous works on photodetectors that employ graphene, MoS2 and h-BN heterostructures to analyze the gap for further improvement. This is the motivation and rational for focusing this review on only graphene, MoS2 and h-BN materials.Although MoS in 2015  and is b2-based [2 heterostructures with/without incorporation of other materials [2 nanohybrid by Choi and team supports the relevance and importance of this review manuscript. They emphasized the potential of synergizing graphene and MoS2 for developing various types of biosensors with higher sensitivity for the biomedical field [2, as well as the insertion of h-BN layers, which is a promising tunnelling layer between graphene and the MoS2 heterostructure, based on previous works, to improve the photovoltaics of the device that contribute to the self-powering effect.Generally, there are many reviews related to photodetectors, especially related to self-powering effects such as self-powering nanoscale photodetectors in 2017  and self2-based  light seaterials ,17,18,192-based heterostructures with/without the insertion of h-BN layers and their relevance for self-powering photodetection applications. Furthermore, the effect of plasmonic coupling with 2D materials towards the performances of photodetection in devices such as photodetectors and solar cells is also reviewed. Although this review emphasizes photodetectors, other devices such as transistors and solar cells with graphene/MoS2 or graphene/h-BN/MoS2 heterostructures are also included to understand the behaviors and physics of these heterostructures, because this review aims to study the impact of material structuring and attribution of plasmonic effects towards the electrical and optical properties, as well as the photovoltaic effect on graphene/MoS2-based devices as a path for self-powering application. Since the majority of the reviewed devices are vertically structured, dimensions are a critical parameter, which is also highlighted in this review. The layout of this review is as such: parameters of photodetectors, 2D materials in photodetectors, plasmonic implementation in photodetectors, numerical modelling for MoS2/h-BN/graphene photodetector and the outlook of this study for the future.Therefore, this review is scoped specifically on the properties and characteristics of graphene/MoSIn general, the performance of a photodetector is based on some of the following key parameters, as shown in Currently, the photodetector market is dominated by silicon-based photodiodes due to the matured fabrication process at low cost. Although silicon is an excellent and abundant semiconductor material, the narrow and indirect bandgap properties of silicon limit the detection spectrum, especially in the near-infrared region, which triggers the search for alternative materials, especially for optoelectronic applications . MateriaPhotodetectors that are developed using non-2D materials only detect light at the ultraviolet spectrum, which limits their applications and development. Therefore, 2D materials are being extensively explored to push the performance limit further . IntenseGenerally, 2D materials have great potential for high-performance photodetectors due to their high crystal quality and unique properties in both electronic and optical aspects such as tunable bandgaps with thickness variations , as well2 and h-BN with their heterostructures in terms of physics and electronic and optical properties. The integration of excellent electrical properties of graphene, especially in terms of ultra-fast carrier mobility and excellent optical properties of MoS2, in terms of large absorption coefficient and gain have been demonstrating significant enhancement in the performance of photodetectors. This is because the beneficial properties from both the materials were combined and the limitations of individual material were tackled by each other, which could contribute towards device performance. Despite intense research on these 2D materials in the past five years, the studies related to photodetectors with graphene and MoS2 heterostructures with/without h-BN were still being reported in 2020. The latest studies showed ultrahigh responsivity and detectivity via channel length reduction and Schottky barrier modulation [2 photodetectors [2 photodetectors in recent works is the motivation and rationale for selecting these materials in this review, as there is room for further investigation in terms of their device physics and fabrication approaches, which can result in improved photodetectors, especially with self-powering mechanisms.As mentioned earlier, there is a list of 2D materials that are being intensively studied for photodetection applications. However, this review highlights three main materials, which are graphene, MoSdulation , as welletectors . Althoug2 and h-BN and focuses on the graphene/h-BN/MoS2 heterostructures in terms of device physics and working principles and device fabrication and highlights previous works on the performance of photodetectors with these heterostructures.This section covers briefly the properties of graphene, MoS2-hybridized carbon atom in a honeycomb lattice structure [Graphene is an sptructure  that hastructure ,29,32,33tructure ,32,33,34tructure ,34, hightructure ,33 and itructure . Graphentructure ,29,35. Ttructure . Graphentructure . The chetructure .2 [Although graphene shows excellent properties for light detecting applications, it is limited by low photoresponsivity, detectivity and quantum efficiency due to its low light absorption coefficient and fast recombination rate  with an 2 . The tun−2 with the carrier concentration of the electron and hole that can be calculated based on the linear Dirac-like dispersion relation, as in Equation (1) [2/Vs for the mechanically exfoliated suspended layer [2/Vs for a graphene layer on silicon dioxide with a stable lattice structure at room temperature [2/Vs compared to a hexagonal boron nitride substrate, which reported carrier mobility up to 100,000 cm2/Vs [Other electrical properties of graphene are also reviewed in this section. The intrinsic carrier concentration of graphene at room temperature is tion (1) . The Fer×106 m/s . The cared layer . Howeverperature ,42 due t0 cm2/Vs . This cl−1 and Besides electrical properties, optical properties of graphene were also studied in previous works ,43. The 2/graphene and WSe2/graphene heterojunctions in graphene-based photodetectors [In the context of a device, the optical responsivity of a graphene-based photodetector is usually poor, which was reported to be in the range of in layer ,33. Thesin layer ,33, incletectors . Moreoveetectors . Nitrogeetectors , which a2), which has Mo atoms sandwiched between two layers of S atoms and has natural availability with ambient/environmental stability [The family of TMDs gained most attention among 2D materials . Generaltability ,29.2 with a thickness of 0.65 nm at the monolayer [2 is the adjustable bandgap from 1.2 eV to 1.8 eV when the material changes from the bulk condition to a monolayer, where it transforms from indirect to direct bandgap material, respectively, due to the quantum confinement effect. Therefore, MoS2 has thickness-dependable optical properties [2 monolayer to five layers and remains constant from five layer onwards, where it behaves as a bulk material [2 increases as the material thickness decreases. The electron affinity of MoS2 is also dependent on the number of layers. The electron affinity values that were reported for monolayer MoS2 were 4.0 eV [2 were 4.0 eV [MoSonolayer  preserveonolayer . It appeonolayer  with theonolayer , a largeonolayer  as well onolayer . The mosoperties ,30,46. Tmaterial ,33. Thuse 4.0 eV , those oe 4.0 eV  and those 4.0 eV . All the2 layer must be carefully chosen for optimum performance, based on application, because the thickness determines the contact Schottky barrier height (SBH), contact resistivity and carrier mobility [2 increases from a monolayer to five layers. Since reduced SBH is preferable for injection of charge carriers, a thicker MoS2 will suit this requirement, but a thicker structure is disadvantageous due to intercoupling resistance. Thus, the preferable thicknesses are in the range of 5 nm to 8 nm, which is about seven to twelve layers. The contact resistivity for MoS2 with thickness below five layers increased drastically due to quantum confinement-induced structure modification and increased slightly for thickness with five layers and above due to increments in the interlayer resistances. This clearly emphasizes again that the thickness of MoS2 must be selected carefully for optimum performance. Moreover, carrier mobility of monolayer MoS2 is lower in fewer layers because both the top and bottom surfaces are exposed to the environment that introduces scattering effect. The intrinsic electron mobility is highest in monolayer MoS2 because the effective mass of electron is reduced from 0.551 mo to 0.483 mo when MoS2 is thinned from bulk to the monolayer. Though the above reviews suggests that thicker MoS2 has better properties, it may not be practical for optoelectronic devices because they opt to utilize the direct bandgap nature that comes from the monolayer MoS2. Thus, an alternative approach is needed to tackle this issue, and the thickness of MoS2 must be tailored accordingly.The thickness of the MoSmobility . SBH red2 with different thicknesses can tune the light absorption wavelength where a multilayer MoS2 phototransistor shows a wide spectrum of detection ranging from ultraviolet to near-infrared, as reported in [2 was reported to be 0.6 × 106 cm−1, and the incident light was mainly absorbed by this layer, which had a thickness of 28 nm because the absorption length was 17 nm [2 with the transformation from direct bandgap to indirect bandgap with variation in the thickness from monolayer to bulk, respectively [2 with thicknesses of 150–165 nm, showed a better rectifying effect compared to MoS2 with a thickness ranging from 70 nm to 120 nm in dark condition [2 is crucial because it influences the optical transparency of the material, which will contribute to the generation rate, as proven in [2 drops from 90% to 40% when the thickness of MoS2 is increased from a monolayer to six layers. However, in the context of MoS2/h-BN/graphene heterostructures, a multilayer MoS2 can establish a vertical depletion region to support tunnelling of photogenerated holes, which is a challenge in monolayer MoS2 due to an extremely thin vertical depletion region [2 layers, especially in a vertical device architecture, is a crucial parameter that must be tailored as it trades off the optical properties of the device, which will contribute to the performance of the photodetectors.MoSorted in . As in tectively . The mulroven in ,52 for s2 does not affect the electrical properties of the device at higher VDS (power supply voltage). However, a significant difference is observed when the voltage drops to zero bias. The photocurrent of the MoS2/graphene photodetector depresses at zero bias and approaches a similar value as the dark current. In contrast, the MoS2/h-BN/graphene photodetector demonstrates better photocurrent at zero bias due to the recovery of the photovoltaic effect. The ultra-thin h-BN layer acts as a barrier to hinder the interlayer transport of electrons, while photogenerated holes in MoS2 can tunnel through the ultra-thin h-BN. This recovers the internal electric field of the device [h-BN is an insulating 2D material that has a lattice constant 1.8% greater than graphene . It is ae device .The h-BN incorporation with semiconductor materials, especially with 2D materials, is being studied. The main focus of those research works pertains to studying the influence of h-BN materials on the entire device performance and tailoring the thickness of the h-BN layer to obtain optimum photocurrent with reduced dark current, which will later contribute to the photoresponsivity of the devices. This was proven based on the work in , where t2 and h-BN heterostructures is covered in this section in order to understand the advances of these heterostructures in photodetection as well as to identify the research gap for further studies, especially in meeting the requirements for self-powering applications.Heterostructure devices based on vdW interactions combine the benefits from each material, and the internal built-in potential in the heterostructure can induce effective photogenerated carrier separation . TherefoBasically, the architecture of photodetectors can be classified into vertical or lateral heterostructures, and this can determine the current flow in the device. Some architectures of photodetectors based on previous studies are as shown in 2-based photodetectors will now be reviewed in this section. Functionalized and hybrid graphene-based photodetectors employ photothermoelectric (PTE), photovoltaic (PV) and photogating (PG) mechanisms for photoresponse, which creates the non-equilibrium distribution of photoexcited carriers and their diffusion and drift in potential gradient. This mechanism depends on the geometry and microscopic carrier dynamics [In general, the device physical mechanism of photodetectors can be classified into photovoltaic effect, photoconductive effect, photothermoelectric effect and photobolometric effect. The principles of these mechanisms were covered in the review by Wang et al. . Two or dynamics . The PTEdynamics .It is important to understand the operation of a hybrid graphene photodetector in order to improve its performance. Light that is shone onto a hybrid graphene-based photodetector is absorbed by the semiconductor if the photon energy is greater than the bandgap of semiconductor materials, thus creating electron–hole pairs, which form an exciton with an intrinsic efficiency. The large electric field or thermal energy influences the creation of free carriers by overcoming the Coulomb force between electrons and holes, which is associated with efficiency. Lastly, the carriers are transferred between semiconductor and graphene in the presence of a potential barrier at the semiconductor–graphene interface or from a charge trapping mechanism in the semiconductor, which contributes to the charge transfer efficiency . Therefo2 heterostructure were studied previously [2 were studied by Rathi and team [2 in this work had contact with titanium at one side and contact with graphene on the other side. This resulted in rectifying characteristics, and the behavior of the device could be tunable with external gate voltage, where the Fermi level of the graphene was shifted upward and downward from the Dirac point with positive and negative gate biasing, respectively. The graphene and MoS2 in this work were p-type and n-type, respectively, and the barrier height between them was tunable based on the doping of graphene compared to a fixed barrier between metal and MoS2. On the one hand, the graphene/MoS2/graphene photodetector in [DS biasing.The performances of photodetectors with graphene/MoSeviously ,19. Elecand team , where t2 heterostructure were improved with the insertion of an h-BN layer in between graphene and MoS2, creating a metal–insulator–semiconductor structure, which contributed to rectifying tunnelling devices. Modelling [2 heterostructures at material and device levels were reported in previous studies. The lattice mismatch between these three materials is reasonably small, as reported in [2/h-BN and h-BN/graphene were 4.5% and 2%, respectively, which was negligible and preserved their intrinsic electronic properties because the layers were combined via weak vdW energy [2 is higher than doped MoS2 at values of −2.3 eV and −1.87 eV at an electric field of 0.1 V/Å, respectively, which also indicates a stable adsorption structure sensitive to the direction of the electric field [The electrical and optical properties from graphene/MoSodelling ,56 and eodelling ,47,54,57orted in , where tic field . This wo2 [2, which was proven through the work done by Liu in [2 were 4.2 eV and 5.8 eV, respectively, which depicted that the Dirac cone was shifted 0.3 eV above the Fermi level, and it was an n-type graphene layer. This resulted in the accumulation of some charges on the right side of h-BN, and some were depleted in the left side. The key finding in terms of dimension was that the intensity of charge transfer in the inner h-BN interlayer was weakened due to the formation of large contact resistance, as shown in Moreover, the degree of charge transfer was highest in graphene and lowest in h-BN, which indicated that h-BN is the barrier for charge transfer between graphene and MoS2 . Thus, ty Liu in  that cony Liu in . The wor2 heterostructures, it is important to review the band diagrams of this heterostructure at negative and positive biasing. A potential step was created between graphene and MoS2 due to the difference in work function in both the materials. When both graphene and MoS2 were brought together, a spontaneous flow of electrons from graphene to MoS2 occurred due to conduction band bending of MoS2 at the interface. However, the h-BN insertion blocked part of the electron movement that resulted in a built-in electric field because of the formation of a dipole at the interface of the h-BN layer. The changes in the band diagram with applied external electric field are shown in 2 interface during forward biasing caused an upward bending of the conduction band and valence band, which resulted in the formation of a barrier for electron flow from graphene to MoS2, and this is expected to contribute to good rectifying characteristics. On the other hand, reverse biasing led to the accumulation of negative charges at the h-BN and MoS2 interface, which resulted in downward band bending of the conduction band of MoS2 that caused an ohmic contact.In order to better understand the electrical operation of devices with graphene/h-BN/MoS2 heterostructure was also analyzed in the context of a photodetector, as shown in 2/h-BN/graphene heterostructure at a flat band model with material parameters of electron affinity, bandgap, electron tunnelling barrier, hole tunnelling barrier and work function of graphene. Based on this figure, it can be interpreted that the graphene in the model is a p-type material, as the Dirac point was shifted 0.2 eV below the Fermi level, which results in a work function of 4.7 eV. The hole tunnelling barrier was 1.2 eV, whereas the electron tunnelling barrier was 2.7 eV. The direct tunnelling of electron from graphene layer was blocked by the high h-BN barrier of 2.7 eV, and the Fowler–Nordheim tunnelling of the hole was negligible due to insufficient minority carriers in MoS2 during the positive biasing without light conditions that resulted in low dark current. However, photogenerated carriers in MoS2 from the photon absorption during the positive biasing with the light condition increase the hole population in the valence band of MoS2, which allows the hole tunnelling from MoS2 to graphene that is attributed to the increment of illuminated current. A similar pattern was observed in negative drain biasing except for some photogenerated electrons that tunneled through the high electron barrier height between graphene and MoS2. Based on these band diagrams, it can be concluded that h-BN layer acted as a barrier for electrons that suppressed the dark current and allowed hole tunnelling during illumination that contributed to a high Ion/Ioff ratio, which was also supported by the work done in [Moreover, the band diagram of graphene/h-BN/MoS done in . It was  done in .2 and h-BN, were reviewed extensively in [2 and Si/SiO2 substrates with polymethyl methacrylate (PMMA); removing the sacrificial SiO2 sacrificial layer with diluted HF aqueous solution, leaving behind floating PMMA/MoS2; transferring PMMA/MoS2 onto a new substrate; and finally removing PMMA with acetone while having MoS2 film on the new substrate [Material synthesis and device fabrication, especially involving graphene, MoSively in ,26,27. Gubstrate .2 and h-BN was studied previously, as reported in [2 on top of h-BN was reported to provide smaller lattice strain, low doping level and a clean and sharp interface by retaining the high carrier mobility in MoS2. The fabrication of vertical structure graphene/MoS2 by Gnanasekar et al. was reviewed in [2 structure was grown onto graphene by using a two-zone CVD reactor, as shown in 2 layer onto graphene, a mechanical transfer approach can also be used in fabricating a graphene/MoS2 structure.A heterostructure of a combination of MoSorted in . The cheiewed in . Graphen2/h-BN/graphene heterostructures, as shown in 2 that was used to study both electrical and optical properties of the device [2/Si substrate, which was in 2 cm × 2 cm. Then, 20 nm thick CVD h-BN with a size of 1 cm × 1 cm was transferred on the graphene layer, which was followed by transferring CVD-grown monolayer of MoS2, with a size of 500 µm × 500 µm, onto the h-BN/graphene sample. The thickness of the entire MIS structure was reported to be less than 30 nm. The top layer was fabricated smaller compared to the bottom layers to prevent current leakage between layers.Some device fabrication approaches for MoSe device . The CVD2/h-BN/graphene photodetector by Li et al. [2/Si substrate. Then, monolayer CVD-grown h-BN was transferred on the graphene using the PMMA method. The photolithography technique was used to pattern and deposit the Au/Cr electrode. A non-conductive gap was created between the electrodes by cutting the h-BN/graphene sample with a probe. Lastly, a few layers of MoS2, which were mechanically exfoliated, were transferred on the h-BN/graphene sample using the dry transfer method with polyvinyl alcohol (PVA). The thickness of MoS2 and h-BN in this device were 28 nm and 0.47 nm, respectively.On the other hand, i et al. . In this2 photodetectors that are being studied in this review paper are highlighted in 2 were grown using the CVD method and were transferred using the wet transfer method, which is suitable for CVD-grown samples [2 in some photodetectors were mechanically exfoliated and integrated by using the dry transfer method.The fabrication processes especially related to the 2D materials were not deeply focused on in this section, because intense reviews were done previously. However, it is important to consider and evaluate the material synthesis and device fabrication approach that are being used because they determine the quality which will be translated in the performance of the device. Therefore, all the synthesis and fabrication approaches for the graphene/h-BN/MoS samples . h-BN an2, h-BN and graphene heterostructures were analyzed based on optical images, Raman spectroscopy, field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM), as reported in the previous works. FESEM analysis was used to study the morphology of a vertically-aligned CVD-grown MoS2 nanosheet on graphene, as reported by Gnanasekar et al. [2 nanosheets with thickness and length of 56 nm and 5 µm, respectively, were reported, and the EDS elementary mapping confirmed homogenous coverage of MoS2 on the graphene layer. Moreover, the high resolution TEM (HRTEM) approach can also be used to study the cross-section of a MoS2/graphene device, such as shown in 2 as a passivation layer, and the intensity profile shows the thicknesses of graphene and MoS2 at values of 0.36 nm and 0.7 nm, respectively, which indicated that both the materials in the heterostructure were monolayers.The morphology, compositional structures and properties of the MoSr et al. , as show2 films with various pre-deposited Mo thicknesses of 1 nm, 2 nm and 5 nm that were employed for flexible photodetector in [2 films that were transferred, as shown in 2 films were 6 nm and 20 nm, which are about 9 and 31 layers, respectively. The large roughness and defects in the sample with pre-deposited Mo with thickness of 1 nm showed that the sample was of a bad quality, and the thickness of MoS2 film was difficult to be determined. Aside from that, the presence and formation of MoS2, h-BN and graphene heterostructures can also be confirmed through optical images such as shown in 2/graphene heterostructure with a channel length of 30 nm, and h-BN served as the gate barrier in this device. However, devices in 2/h-BN/graphene heterostructures with vertical device architecture, where the dotted and dashed lines indicate the presence of graphene and MoS2 layers, respectively.Moreover, MoSector in  were cha−1) and 2D (2960 cm−1), and shows in-plane and out-plane vibration. The number of graphene layers can be determined based on the ratio of intensities of 2D and G peaks, position and shape of the peaks. The G peak can indicate the number of graphene layers, and the frequency of this peak decreases as the number of layers increases [2 has two Raman peaks, which are E12G and A1G, and the difference between these two peaks indicates the number of layers. The Raman peak for h-BN crystal is 1336 cm−1 and experiences blue and red shifts due to shorter phonon modes in single layer h-BN, and random strain due to stripping process in double h-BN, respectively [2, h-BN and graphene heterostructures based on previous works are shown in 2 in this heterostructure was confirmed to be a monolayer based on the difference between Raman E12G and A1G peaks, which is about 19 cm−1. The G and 2D peaks for graphene were reported to be 1581.5 cm−1 and 2695.9 cm−1, which are approximately reaching the values of monolayer graphene.On the other hand, the properties of the materials can be determined based on the intensity peaks in Raman spectroscopy. A monolayer graphene has two Raman peaks, which are G  nanosheet studied in [x-axis) and diffraction plane (y-axis). The most intense peak indicates a strong tendency of adaption to the crystal orientation during the growth process. As in 2, which denoted that the V–MoS2 nanosheets were highly (002) orientated. The absorption peaks of A and B were located at 600–700 nm, agreeing with 2H phase V–MoS2 nanosheets. Moreover, the photoluminescence (PL) spectra for graphene/h-BN/MoS2 heterostructures were studied in previous works [2, as shown in 2/h-BN/graphene was improved compared to the MoS2/graphene heterostructure. This supported the proposal by Li et al. for improving the photovoltaic effect in the MoS2/graphene photodetector with h-BN insertion for self-powering applications [2 [In addition, the crystallinity and quality of materials were also confirmed based on XRD, the UV–visible absorption spectrum and the photoluminescence (PL) spectrum. udied in . XRD resus works ,30 for cications . Similar2 and graphene/h-BN/MoS2 heterostructures to study their relevance for self-powering photodetections. The MoS2/bulk silicon heterojunction photodetector, which was studied by Deng et al., supported and showed that the device fabrication demonstrated good compatibility with the silicon CMOS process while achieving excellent photoresponsivity at 1.7 × 104 A/W with rise and fall times of 1.44 ms and 1.45 ms, respectively, at the near infrared spectrum [The continuation from material characterizations is the analysis of device performances, because these two aspects are interrelated. The device performances of graphene-based photodetectors especially with the heterostructures were reviewed intensively by Shin et al. . They cospectrum . This sh2/graphene photodetector that was fabricated in 2015 showed maximum responsivity of 2.06 × 103 AW−1 at incident light with an optical power of 14 mW cm−2 at a wavelength of 520 nm, which was claimed to be higher than previous work [2/graphene photodetector was fabricated and studied by Liu et al. without complex transfer and alignment processes. This lateral device showed a maximum specific detectivity of 1013, responsivity of 2 × 103 mA/W and on/off ratio up to 106 (which indicates low dark current) at the visible light spectrum [2/graphene that had a channel length of 30 nm. Light and gate biasing were used to tune the Schottky barrier, which resulted in improved photocurrent and low dark current with a responsivity of 2.2 × 105 A/W and a detectivity of 3.5 × 1013 Jones [L is the channel length, µ is carrier mobility and DSV is the drain voltage.Moreover, a MoSous work . To justspectrum . A simil13 Jones . They us2/h-BN/graphene heterostructure as a metal–insulator–semiconductor (MIS) diode when the device was illuminated with visible light at 688 nm with an optical power of 7 mW and a light power density of 2.8 W/m2. The thickness of this device structure was a monolayer of MoS2 with an h-BN of 20 nm. The entire thickness of this device was below 30 nm. The photocurrent/dark current ratio was around 6.6 with photoresponsivity of 0.3 mA/W as well as decay and rise time of 11 s and 10 s, respectively. The findings were claimed to be ten times higher than the graphene/MoS2 heterostructure that was reported earlier.In 2016, Jeong et al.  had stud2 and graphene strips that sandwiched h-BN was reported by Vu et al. [5, a high photoresponsivity of 180 A/W and an ultra-high photo detectivity of 2 that was transferred with the dry transfer approach. As mentioned earlier, mechanically exfoliated materials have better crystal quality with freshly cleaved surfaces [2, which has a thickness of 0.65 nm. However, the thicknesses of graphene and h-BN were different. These dimensions are considered as crucial, since the layers in the device are vertically structured.In the following year, a similar type of study on photodetector with single-layer MoSu et al. . The thidiode in  were grodiode in  was prepsurfaces . Secondl2/h-BN/graphene that were discussed previously are compiled in 2/graphene photodetector was proposed by Li et al. [2 and single layer graphene in their optical studies. However, they claimed that the h-BN had no active role in their device because the single layer graphene was in direct contact with the MoS2 layers. 2 and graphene was at 0.23 eV with small bending of 0.09 eV in MoS2, which allowed leakage of electrons from MoS2 to graphene that resulted in increased dark current, even at zero biasing. Thus, this leakage was stopped with the insertion of h-BN, where it acted as a barrier to block the interlayer movement of electrons and only allowed tunnelling of photogenerated holes from MoS2 to graphene with the internal electric field. Therefore, the dark current was suppressed more at zero bias, which resulted in an on/off ratio of 1000. This was considered as recovering the photovoltaic effect in the device, which is beneficial for self-powering photodetection.The I–V characteristics of photodetectors with MoSi et al. , where t2/graphene photodetector [2. The influence of h-BN thickness on the performance of photodetectors is shown in Nevertheless, dark current was also lowered in the lateral graphene/MoSdetector , as show2 and h-BN heterostructures that were discussed in this section are tabulated in A list of photodetectors that utilizes the graphene, MoS2 heterostructures. The ultimate goal of these studies was to improve the performance of the device based on the figure of merit discussed in 2 at ±1 V were demonstrated in thick MoS2 compared to linear characteristics in thin MoS2, which has ohmic contact between MoS2 and the Au electrode. A multilayer MoS2 transistor has increased current under illumination of red, green and UV light in vacuum, which is dominant in p-type transfer and n-type conduction under dark and illuminated conditions, respectively [2 for self-powering applications, indicating the importance of tailoring the thickness of the absorbing layer. The optimum individual thickness of each layer was reported with an analysis of their properties and performances. However, tailoring the thicknesses of all the layers to obtain one optimum system is still lacking and needs much attention. 2/h-BN/graphene photodetectors that have potential in contributing to self-powering application.The prospect of 2D materials with their challenges and market study was reported in . Based oectively . This st2 structures, will be reviewed.Modification of the photodetector detection surface with light sensitizer effects such as quantum dots ,67, dye 2/graphene devices, showed better sensitivity compared to embedding Au NPs on either MoS2 or graphene [2 showed a threefold enhancement of photocurrent response due to enhanced near-field oscillation and the scattering effect of nanoparticles [The interaction between the electromagnetic wave and free electrons in the metal is known as surface plasmon resonance (SPR), in which the light (electromagnetic wave) excites free electrons in the metal to achieve selected absorption or reflection, producing an enhancement in light intensity and trapping electromagnetic energy in deep subwavelength volume, area or length ,75,76. Sgraphene . Au nanoarticles .A previous review of plasmonic photodetectors highlighted that the embedment of plasmonic coupling concept into the photodetector opens up the potential for shrinking the size of photonic devices to the nano scale with a higher speed and wider frequency spectrum of applications by employing the ability of the metal to constrain light at deep sub-wavelengths . The utiIncorporation of plasmonic nanoparticle scattering towards performance enhancement in photovoltaic and photodetector devices was discussed in  by analyBesides the shapes, size and material of nanoparticles, the location of nanoparticle embedment can influence the LSPR effect in the photodetector. Metal nanoparticles can be embedded based on deposition at the top of the detection medium, integrating below the detecting medium or embedding within the detecting medium . Nanopar−1 The shift between G and 2D peaks and presence of D peaks in this Raman spectra clearly signify that bilayer graphene, which was obtained based on ratio of peak intensities (I2D/IG), were transferred on the Au thin film with large defect density [2 [Before analyzing the performance of photodetectors with plasmonic coupling, it is important to understand the material characterizations, as these confirm the quality and physics of plasmonic effects.  density ,85. On t density  based onnsity [2 .2 for device enhancement was reported in 2013 by Lin et al., where the photocurrent in the transistor was improved by decorating the MoS2 with Au NPs [2 transistor decorated with Au NPs under illumination of light at a wavelength of 514 nm with the scanning electron microscopy image of Au NPs on the MoS2 and the electrical characteristic that indicates the improvement of photocurrent with the presence of Au NPs. Interestingly, they highlighted the increment in charge carrier mobility and electron concentration in both dark and illuminated conditions when the device was decorated with Au NPs. This confirmed the potential of utilizing the plasmonic effect in the MoS2, which acts as the absorber in the MoS2/h-BN/graphene heterostructures.Incorporation of the plasmonic effect with MoSh Au NPs . Figure 4 A/W as well as rise and fall times of 18 s and 7 s, respectively, at an illumination wavelength of 610 nm [2 as the channel of the phototransistor. Study of the effect of NP size with light absorption and intensity of the device was also done in this work. Samples coated with Ag NPs at particle sizes from 13 nm to 25 nm showed obvious enhancement of intensity compared to Ag NPs with sizes exceeding 40 nm, which led to decreased intensity due to the shield effect of scattering and metallic absorption. A similar plasmonic approach was used by Gosh et al. in 2019, where Ag NPs at sizes ranging from 5 to 14 nm with a mean size of 11 nm were synthesized and added with organic layers of PEDOT:PSS to fabricate a plasmonic hole-transport-layer enabled self-powered hybrid perovskite photodetector [Work done by Jing et al. in 2017 reported 470% improvement with a responsivity of 2.97 × 10f 610 nm . They modetector . This wo2 by [Beside using Ag NPs, a study on a photodetector employing porous Ag/TiO2 by  was repoOC) of the device was studied. The self-powered ultraviolet photodetector based on a TENG configuration with the implementation of plasmonic Ag NPs in this work was proposed for the first time.On the other hand, Reddeppa et al. in 2019, studied Au NP-functionalized rGO/GaN nanorods (NRs) . SphericBased on the previous work, various plasmonic approaches were used in photodetectors. The review mainly focused on Ag- and Au-based NPs ,72,88. T2/h-BN/graphene heterostructure that can contribute to the photovoltaic or built-in potential of photodetectors for self-powering applications. Therefore, the non-destructive approach with reasonable timing, cost-efficiency and a large number of samples to mimic the existing device structures for further study and enhancement will be the theoretical modelling and numerical modelling of the device. Computational studies are appealing tools to mimic the chemico-physical properties and behaviors of a system, which results in utmost importance in explaining and foreseeing the system’s behaviors or capabilities. For instance, the modelling work by Zan et al. [2 design [Based on the reviews of materials and plasmonic coupling in n et al.  with den2 design . Current2 design , density2 design ,89, Quan2 design , molecul2 design , 1D-Sola2 design , COMSOL 2 design  and Tech2/h-BN/graphene heterostructure will be reviewed. Previously, graphene [2 [2/h-BN/graphene photodetector, which was adapted from [In this section, the potential of numerical modelling using Silvaco TCAD for photodetectors based on MoSgraphene ,91,92,93phene [2  materialted from , was repted from . This sited from  in order2-structured devices like photodetectors/solar cells. Therefore, the successful modelling in [2 heterostructures at the device level. The photogeneration rate from structural analysis and current density results from this work, as shown in 2 layer and gradually decreased at graphene and silicon layers at values of 14.8, 12.9 and 11.4 photons/scm3, respectively. This indicates that the modelled MoS2 layer had absorbed most of the incident and acted as the absorber, which supports the principle that was highlighted in the device physics. Furthermore, the carrier current density of this model was studied through the cutline at the x-axis and showed that electron current density was dominant at the MoS2 layer, and hole current density was dominant at the interface of h-BN/graphene, which supports the carrier transport findings as reported in [2/h-BN/graphene heterostructures towards the behavior and performance of photodetectors.To date and to the best of the authors’ knowledge, previous numerical modelling in Silvaco ATLAS highlighted graphene-structured or graphene/MoSlling in , as showorted in . FurtherSelf-powering photodetectors convert optical signal to an electrical signal without the need for an external power supply. The performances of the devices are measured based on the performance parameters of photodetectors, which were outlined in 2. The combination of superior electrical properties of graphene with the decent optical properties of MoS2 make the performance of MoS2/graphene hybridized photodetectors much better than the photodetectors with individual graphene or MoS2 materials. In this case, MoS2 acts as the light sensitizer that absorbs the light, whereas graphene acts as the charge transport layer, which contributes to improved responsivity with higher operation speed of the photodetector. Despite that, suppression of photocurrent and high leakage current at zero bias limits the potential of MoS2/graphene photodetectors for self-powering applications. Past studies proposed insertion of a tunnelling layer such as h-BN between these two materials to tackle performance issues in self-powered photodetectors.Various types of 2D materials were extensively studied in recent years for photodetection applications. Some specifically focused on implementation of 2D materials for self-powering effects. The most commonly ventured 2D materials to date are graphene and MoS2 based on previous studies, which demonstrated improved photodetection performances. However, there is room for further research in this area, since the incorporation of hybridized 2D materials such as MoS2/h-BN/graphene with plasmonic nanoparticles has not been fully explored. Tailoring the dimensions of this device structure in both vertical and lateral aspects with decorations of plasmonic nanoparticles is necessary for the optimal performance of self-powering photodetectors. The dark current and photocurrent are trade-off parameters with respect to the thickness of the h-BN layer. It is expected that the dark current will be reduced with the increment of h-BN thickness and trade-offs with the photocurrent. This can be countered by improving the absorption in the photodetector with NPs, which can contribute to improved photocurrent.On the other hand, metal NPs showed their effectiveness in improving photoresponse by increasing the photon scattering and absorption either by increasing LSPR or contributing to the extraction and transportation of carriers under illumination. Studies also proved that the shape and size of NPs are critical parameters in optimizing the performance contribution of NPs. Plasmonic coupling can be employed to both graphene and MoS


To set up an online peer-led medical education programme for core psychiatry trainees during the COVID-19 pandemic.To determine trainees’ views regarding the role of peer-led education in psychiatry.A peer-led education programme was set up for psychiatry trainees in their third year of core training, held over an online video-conferencing platform. The weekly sessions were organised and led by trainees. Each week a trainee either presented a journal article or a particular psychiatric topic, with a group discussion afterwards.An online survey was sent to psychiatry trainees that had participated in the programme to determine their views. Close-ended questions were asked as well as open-ended questions for more qualitative responses.There were 9 peer-led sessions in total, with 11 trainees (out of 18 invited) attending at least one session, and an average of 5 trainees at each session.Five core trainee psychiatrists responded to the survey following the sessions. All of the respondents found the sessions either “very” or “fairly” useful. 80% stated that there should be more peer teaching opportunities as part of normal psychiatry training. All respondents found engaging with online teaching either “easy” or “OK”.Open-ended questions showed that respondents found the sessions were useful for: 1) connecting with peers during a difficult time 2) free discussion due to being around peers 3) wide interest and variety of topics. Improvements that could have been made were: 1) more sessions 2) advance knowledge of journal articles being presented.Peer-led sessions are a useful form of medical education for core psychiatry trainees. During the restrictions brought about by the COVID-19 pandemic they are a way to connect with colleagues during an isolating time. They are easy to organise and access; and can take pressure off medical institutions, whilst having the advantages of allowing trainees to feel they can discuss topics in a more open manner and can follow their own interests.


Conclusions: There are significant variations in sarcoidosis mortality within the US. Sarcoidosis mortality was strongly associated with state health disparities. The current study suggests sarcoidosis mortality could be an indicator to reflect the state-level health care disparities in the US.Background: Sarcoidosis is associated with significant morbidity and rising health care utilization, which contribute to the health care burden and disease outcome. In the United States (US), evaluation of sarcoidosis mortality by individual states has not been investigated. Methods: We examined sarcoidosis mortality data for 1999–2018 from the Centers for Disease Control and Prevention (CDC). America’s Health Rankings (AHR) assesses the nation’s health on a state-by-state basis to determine state health rankings. The numbers of certified Sarcoidosis Clinics within the US were obtained from World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG) and Foundation for Sarcoidosis Research (FSR). The associations between sarcoidosis mortality and state health disparities were calculated by linear regression analyses. Results: From 1999 to 2018, the mean age-adjusted mortality rate (AAMR) in all populations, African Americans and European Americans were 2.9, 14.8, and 1.4 per 1,000,000 population, respectively. South Carolina had the highest AAMR for all populations  and African Americans . Both Utah and Vermont had the highest AAMR for European Americans . New York State and South Atlantic had the largest numbers of FSR-WASOG Sarcoidosis Clinics . States with better health rankings were significantly associated with lower AAMR in all population (R Sarcoidosis is a multisystem granulomatous disease of unknown origin that mainly affects lungs, lymph nodes, skin, and eyes . Racial Sarcoidosis is associated with significant morbidity and rising health care utilization, which contribute to the health care burden and disease outcome ,8. DespiMortality data for 1999–2018 were obtained from the Centers for Disease Control and Prevention, Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Data are based on death certificates for US residents and sarcoidosis-related mortality was defined as all decedents with International Classification of Diseases, 10th Revision (ICD-10) D86 codes as the underlying cause of death. Age-adjusted mortality rates (AAMR) per 1,000,000 population per year were generated from CDC WONDER based on weighting averages of the age-specific death rates and comparing with relative mortality risk among 2000 US standard populations.America’s Health Rankings (AHR) was built in 1990 and partnered with the United Health Foundation and the American Public Health Association. AHR assesses the nation’s health on a state-by-state basis with different measures to determine the 50 US states’ health rankings annually, with “1” being the healthiest state and “50” the least healthy state. The state health rankings are a composite index of health measures and calculated by adding each ranked component multiplied by its assigned weight in five core measures : 25% for Behaviors , 22.5% for Community & Environment , 12.5% for Policy , 15% for Clinical Care , and 25% for Outcomes . We obtained twenty-year averages of Overall health value, All Determinants value, and All Outcomes value from AHR and calculated the state health rankings for 1999–2018 respectively.World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG) is a unique organization for the diagnosis and treatment of sarcoidosis and related conditions. WASOG partnered with the Foundation for Sarcoidosis Research (FSR) to provide a platform recognizing institutions as certified Sarcoidosis Clinics. We obtained the numbers of certified Sarcoidosis Clinics within the US from WASOG and divided them into 2 groups (states with and without Sarcoidosis Clinics) and 9 geographic divisions defined by the United States Census Bureau.SAS®  and Microsoft Excel , with p-Values < 0.05 in two-sided T-tests to indicate statistical significance.We thereafter generated scatterplots of Overall health rankings, All Determinants health rankings, All Outcome health rankings by state, and Sarcoidosis Clinics numbers versus Sarcoidosis AAMR, respectively. Univariate linear regression analyses were performed using the following formulas to evaluate the association between sarcoidosis AAMR, state health rankings, and Sarcoidosis Clinics: Sarcoidosis AAMR = Overall Health Rankings × β + α; Sarcoidosis AAMR = All Determinants health rankings × β + α; Sarcoidosis AAMR = All Outcome health rankings × β + α; Sarcoidosis AAMR = States with or without Sarcoidosis Clinics × β + α; Sarcoidosis AAMR = Sarcoidosis Clinics numbers × β + α. Statistical analyses and data management were performed using Statistics Software From 1999 to 2018, a total of 50,567,774 deaths occurred in the US, and sarcoidosis was documented as the underlying cause of death in 18,877 decedents . The overall 20-year sarcoidosis-related AAMR in all populations, African Americans and European Americans were 2.9, 14.8, and 1.4 per 1,000,000 population, respectively. There was a remarkable geographic variation in AAMR by race. The highest AAMR for all populations was recorded in South Carolina  and the lowest in Arizona . South Carolina also had the highest AAMR for African Americans  and Nevada had the lowest AAMR for African Americans . For European Americans, the lowest AAMR was also reported in Arizona  and the highest in both Utah and Vermont . 2 = 0.170, p = 0.003; R2 = 0.286, p < 0.001; R2 = 0.095, p = 0.033, 2 = 0.223, p < 0.001; R2 = 0.095, p = 0.035; R2 = 0.248, p < 0.001, 2 = 0.023, p = 0.389; R2 = 1.66 × 10-5, p = 0.981; R2 = 0.044, p = 0.226, p = 0.018), but there was no statistical difference in European Americans (p = 0.08) and African Americans (p = 0.88). Regarding geographic divisions, South Atlantic had the largest numbers of Sarcoidosis Clinics (13), the highest AAMR  for all population, and the second highest AAMR  for African Americans. In contrast, New England had the smallest number of Sarcoidosis Clinics (3) but the highest AAMR  for European Americans. Divisions with larger numbers of Sarcoidosis Clinics were associated with higher AAMR in all population and African Americans .This study demonstrates geographic differences in sarcoidosis-related mortality in the US for 1999–2018, and to our knowledge, the first-ever assessment to evaluate the association between sarcoidosis-related AAMR and state-level health disparities. The mapping of sarcoidosis-related AAMR shows the different distribution for all populations, African Americans and European Americans. The highest AAMR for all populations was found in South Carolina, Maryland, and Alabama whereas the lowest in Arizona, New Mexico, and Nevada. For African Americans, the highest AAMR was seen in South Carolina, North Carolina, and West Virginia but the lowest in Nevada, Arizona, and Florida. In regard to European American, Northeastern states, including Vermont, Maine, and Rhode Island, had a higher AAMR than most southern states. These geographic findings are similar to the previous studies by Swigris et al.  and MirsSarcoidosis-related mortality is affected by the management of long-term complications and the effectiveness of treatments including corticosteroids, cytotoxic drugs, and biologic agents ,19,20,21There is a paradoxical association of state health rankings with sarcoidosis-related AAMR in European Americans. In our study, the Northeastern states have better health rankings, yet paradoxically higher mortality rates. One possible explanation is the heterogeneity in disease presentation and severity among different ethnic-racial backgrounds and the inconsistency of health care ability to identify the disease in different states. Establishing a definitive diagnosis for sarcoidosis can be challenging. Diagnosis of sarcoidosis is based on specific radiographic and pathologic findings in the setting of a compatible clinical presentation and exclusion of alternative diagnoses. A number of studies indicated European Americans tend to present with asymptomatic and chronic disease compared to African Americans ,34,35. TFSR-WASOG Sarcoidosis Clinics are certified institutions that provide multidisciplinary care to patients with all forms of sarcoidosis. Among 50 states and 9 geographic divisions, New York State and South Atlantic have the largest numbers of FSR-WASOG Sarcoidosis Clinics . In the US, most Sarcoidosis Clinics are affiliated with university hospitals and built based on patients’ needs. Therefore, the law of supply and demand is a key point that could explain the relationship between Sarcoidosis Clinics numbers and sarcoidosis-related AAMR, suggesting states with Sarcoidosis Clinics have higher AAMR in all population compared to those without Sarcoidosis Clinics and divisions with higher AAMR tend to have larger numbers of Sarcoidosis Clinics for all population and African Americans. Sarcoidosis Clinics visit advanced and complicated patients that are at higher risk of mortality.There are some strengths and limitations to our study. The standardized methods and measures using national population-based surveillance and relatively easy website-based analysis tool to obtain the underlying cause of death data and state health rankings in the US are our strengths ,6. HowevOverall, our study showed clear racial and geographic differences in sarcoidosis-related AAMR in the US and its marked association with state health rankings and the numbers of Sarcoidosis Clinics. The current study suggests sarcoidosis-related AAMR could be an indicator to reflect the health care disparities between states and the improvement of overall health status in the US may also improve the mortality rates of sarcoidosis.


In this work, we present an interferometric polymer-based electro-optical device, integrated with an embedded double-monolayer graphene capacitor for biosensing applications. An external voltage across the capacitor applies an electric field to the graphene layers modifying their surface charge density and the Fermi level position in these layers. This in turn changes the electro-optic properties of the graphene layers making absorption in the waveguide tunable with external voltages. Simultaneously, it is possible to appreciate that this phenomenon contributes to the maximization of the light-graphene interaction by evanescent wave in the sensing area. As a result, it is obtained large phase changes at the output of the interferometer, as a function of small variations in the refractive index in the cladding area, which significantly increasing the sensitivity of the device. The optimum interaction length obtained was 1.24 cm considering a cladding refractive index of 1.33. An absorption change of 129 dB/mm was demonstrated. This result combined with the photonic device based on polymer technology may enable a low-cost solution for biosensing applications in Point of Care (PoC) platform. Graphene has gained considerable attention when its unique properties have been reported in 2004 ,2. SinceGraphene can provide a high and very broadband optical absorption extending from visible to infrared range . This abSome features such as immunity to electromagnetic interference, high-speed operation, low power consumption, potential use in harsh environments, miniaturization, integration and multiplexing capability, mechanical stability, low-cost for fabrication, and real-time and label-less detection ,27,28, hMost of the integrated photonic biosensors are based on silicon, due to the excellent optical characteristics that these materials present, demonstrating high sensitivities and a high reproducibility rate. However, despite all the benefits that silicon has, effects such as Two-Photon Absorption (TPA) and Free-Carrier Dispersion (FCD) can become evident, which would compromise the performance of said biosensor . TherefoThe implementation of polymeric photonic devices, integrated with a graphene-based capacitive structure in a single device, will provide the conditions for obtaining an electro-optical biosensor with a wide evanescent field in the sensing area, and with low loss due to tunable absorption based on Fermi level control.In this paper, we present a low-loss electro-optical polymer-based device, with an embedded double-layer graphene capacitor for biosensing applications. Our proposal demonstrates through theoretical analysis and numerical simulations the widening of the evanescent field and consequently, the increase in the sensitivity of the proposed device, due to the interaction generated between the electric field in the capacitive structure and the confined optical waveform. In this sense, a bulk sensitivity of 2828 nm/RIU and a surface sensitivity of 2021.85 nm/RIU were demonstrated for the proposed integrated photonic biosensor, both working with a gate voltage of An efficient use of graphene in these applications requires geometries that provide the correct interaction between the applied electrical fields in the graphene layers , and theIn this study, the Finite Element Method (FEM) was used for analyzing the sensor’s behavior by using commercial software COMSOL Multiphysics. The refractive index used in the core of the waveguide was 1.57 @ 800 nm wavelength, in the substrate it was 1.45 @ 800 nm wavelength, in the cladding of the sensor area it was varied between 1.33 and 1.38, and in the PMMA cladding it was 1.49 @ 800 nm.electrostatics, which is responsible for the generation of the surface current, through a potential applied on the ohmic contacts, as can be seen in Our simulations were performed in two stages, first, the interaction between the projected waveguide and the graphene-based capacitor was analyzed using modal analysis. The number of elements used for this stage was 40,437. In addition, two physics were implemented to simulate the device. The first one, electromagnetic waves physics was implemented to generate the modal distribution at j is the surface current density, E is the electric field applied in the region, both by the voltage terminals and by the electromagnetic waves, demonstrating the perturbation generated to the optical mode by externally applied electric fields.In addition, the electromagnetic waves physics with 92,174 elements, to analyze the spectral response of the projected MZI with all the elements previously mentioned, presenting the expected phase change in the proposed photonic device, as a function of small variations in the sensing area.Similarly, in the second stage we use the same The proposed simulation model is composed of a Mach Zehnder Interferometer (MZI) based on SU-8 polymer with 700 nm width and 450 nm height, on a Silicon Dioxide ϵ, asIn According to Equations  and 3),,3), it iNext, we calculated the real and imaginary parts of the effective refractive index for the TE and TM modes, in order to choose the most suitable mode of operation for our study. In Achieving the best evanescent field in the sensing area while keeping the optical mode as confined as possible in the reference arm, is essential, Equation . In thisConsidering the Equation , and setThe expected result should guarantee a wide evanescent field in the sensing area allowing the largest possible d of dielectric layer of the capacitor in order to tune the Fermi energy of the graphene with low power, maximizing the sensitivity of the proposed sensor. As described by Equations ,,d of died from 20 nm to 5 nm thickness, it is possible to observe a shift in the maximum value reached by the effective refractive index from 44 V to 11 V, observing a reduction in the power required to tune the optical absorption of the graphene in approximately 40 V. This can be seen in By reducing Similarly, we analyzed the biosensor response as a function of the We reported, by simulations, that tuning the Fermi energy level of the graphene enables the electro-optical modification in the sensor, according to Equation . The absTo evaluate the performance of the proposed sensor, we conducted simulations in frequency domain, evaluating the complete layout using Finite Element Method (FEM) in COMSOL Multiphysics.The effective refractive indices calculated in the previous section for the corresponding sensing area and for the complementary section of the MZI, were incorporated in this simulation system, considering the variation that the refractive index presents between 400 nm and 800 nm wavelengths.In order to optimize the total length of the sensing area  platform, for the early detection of genetic and infectious diseases.


PARK2 gene, while, in sporadic PD, the activity and abundance of this protein can be compromised by stress-related modifications. Intriguingly, research in recent years has shown that parkin depletion is not limited to PD but is also observed in other neurodegenerative diseases—especially those characterized by TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we discuss the evidence of parkin downregulation in these disease phenotypes, its emerging connections with TDP-43, and its possible functional implications.Parkin and PINK1 are key regulators of mitophagy, an autophagic pathway for selective elimination of dysfunctional mitochondria. To this date, parkin depletion has been associated with recessive early onset Parkinson’s disease (PD) caused by loss-of-function mutations in the  Frontotemporal dementia (FTD) is the second most common type of early onset dementia under 65 years of age, characterized by atrophy of the frontal and temporal lobes resulting in behavioral and/or language dysfunction ,2,3. AmyThe common hallmark of sporadic and the majority of the genetic forms of ALS–FTSD is TDP-43 (transactive response DNA-binding protein 43 kDa) pathology, characterized by TDP-43 protein depletion from the nucleus and its cytoplasmic aggregation ,11. Thissubstantia nigra, the brain region producing neurotransmitter dopamine (DA). PD is clinically characterized by bradykinesia, resting tremor, and rigidity [PARK(1–23) genes [Parkinson’s disease (PD) is a neurodegenerative disease with progressive death of dopaminergic neurons in the rigidity . Around 3) genes ,16.PARK2 mutations [Mitochondrial dysfunction has been extensively described in sporadic and genetic forms of ALS–FTSD and PD . In partutations  has gainutations   “a sensor of mitochondrial damage” . Under nIn response to mitochondrial stress, PINK1 normal processing is hindered. As a consequence, it gets anchored to the translocase of the outer mitochondrial membrane (TOMM) complex where subsequent PINK1 autophosphorylation leads to its auto-activation ,33.Further to this, PINK1 recruits parkin along with ubiquitin onto damaged mitochondria and activates them through phosphorylation on Ser65 . To enhaActivated parkin ubiquitinates several mitochondrial outer membrane proteins , tagging them for proteasome degradation with long ubiquitin chains ,34. SubsPARK2 and PARK6 are the most common known causes of autosomal recessive early onset parkinsonism  and account for c.a. 5% of familial PD [Homozygous mutations in ilial PD ,36  with only mild parkinsonism [Finally, biallelic insonism .PARK2 or PARK6 mutations occur with similar frequency in patients with sporadic PD and healthy individuals; their estimated penetrance is around 1–25%, and their role in pathogenesis is still not well understood [PARK2 or PARK6 mutation are usually free of clinical motor symptoms; however, some of them can present clinical signs of parkinsonism [PARK2 or PARK6 mutation show a stronger increase of cortical-motor-related activity during execution of self-initiated movements in functional magnetic resonance imaging (fMRI) studies, thus indicating additional recruitment of motor cortical areas during simple motor tasks, as is suggestive of compensatory response [PARK2 mutation carriers [PARK2 mutation carriers is very low [Single heterozygous derstood ,46,47,48insonism ,50 and minsonism . Asymptoresponse ,53. Therresponse ,55. Subcvery low . FinallyPARK2 or PARK6 mutation is a reduction in enzymatic activity of ubiquitin ligase and kinase, respectively, leading to functional haploinsufficiency, unable to secure normal nigrostriatal activity [A possible molecular explanation for the observed abnormal nigrostriatal dysfunction in heterozygous carriers of activity ,57. Indeactivity . HeterozPARK2/PARK6 variants representing a strong risk factor for Parkinson’s disease [Independently of the mechanism, those mutations likely interfere with the protective functions of the PINK1/parkin-mediated mitochondrial quality control . In conc disease , whetherParkin activity can be compromised by post-translational modifications, such as oxidative, nitrosative, or dopamine-related stress, which has implications for patients with sporadic PD and Lewy body neuropathology, as reviewed in References ,60.TAR DNA-Binding Protein-43 (TDP-43) was first identified in 2001 as a protein able to bind the HIV-1 TAR binding sequence , and in In pathological aggregates, TDP-43 is subject to various post-translational modifications that include ubiquitination, phosphorylation, acetylation, sumoylation and is also cleaved to generate C-terminal fragments . From a Interestingly, apart from Parkinson’s disease, decreased levels of parkin have been found in several TDP-43 proteinopathies C. To thiPARK2 [PARK2 pre-mRNA possesses multiple TDP-43 binding sites, suggesting that the control of its stability depends on TDP-43 RNA binding function, at least partially [At the mechanistic level of RNA processing, TDP-43 has turned out to be crucial for the maintenance of brain enriched mRNAs with long introns (>100 kb) such as PARK2 ,21. Indeartially   brains compared to controls and a few cellular TDP-43 overexpression models [Supporting the notion of parkin being a direct target for TDP-43, a significant increase in n models ,93,94. Tn models ,94,96  insoluble aggregates in the cytoplasm via the mechanism of TDP-43 overexpression–related impairment of the proteasomal activity . To confla model .At present, there is no satisfactory explanation for the observed differences between TDP-43 overexpression experiments. In contrast to TDP-43 knockdown, it should nonetheless be considered that TDP-43 overexpression levels may vary substantially between different labs/experimental systems. At the cellular level, this may result in the overexpressed TDP-43 binding/interacting with different partners, depending on the absolute level of overexpression reached during the study. If this could be the case, it would not be surprising that different overexpression levels could even have opposite effects on parkin expression. Of course, such a possibility would have to be experimentally tested and this is an area that certainly deserves further investigation.Notwithstanding the fact parkin levels are regulated by TDP-43, it has been shown that parkin, in turn, can affect the state of TDP-43 within cells. In particular, Hebron et al. have shown that parkin promoted Lys-48- and Lys-63-linked ubiquitination of TDP-43 and formed a multi-protein complex with histone deacetylase 6 (HDAC6) inducing sequestration of TDP-43 into cytosolic inclusions . Co-exprPARK2 mutations lead to complete parkin depletion in patients with PD [PARK2 mutations remains yet to be determined , did not change any mitochondrial parameters, thus indicating the importance of the dose [While biallelic  with PD ,99 , cases with behavioral and/or cognitive impairment without dementia , ALS–parkinsonism/dementia complex , and other mixed variants .ALS–FTSD is predominantly associated with TDP-43 proteinopathy , ALS beiC9orf72, PGRN, and TARDBP [First of all, it is important to keep in mind that cases of ALS–FTSD that have not been genetically defined may present other types of pathology . For this reason, in this review we focus on parkinsonism in genetic forms of ALS–FTSD with confirmed TDP-43 proteinopathy, caused by mutations in d TARDBP ,112,113.MAPT mutation, so the term frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) was coined [Regarding FTLD it is interesting to note that the first links between this disease and parkinsonism extend before the recognition of TDP-43 proteinopathies. Indeed, until a few decades ago parkinsonian symptoms were regarded as a rare manifestation of FTLD associated with s coined . More res coined ,116,117 s coined .PGRN mutations) or with MND .Usually, FTLD is associated with either parkinsonian symptoms  [with MND ,123. In of cases . ImportaAT-Scan) . UnfortuTARDBP mutations may have a broader symptomatic spectrum than other gene mutations in FTLD, as they may be associated with all three conditions: ALS, FTLD, and parkinsonism [It seems that insonism .At the clinical level, parkinsonism in FTLD syndromes is typically characterized by akinetic–rigid phenotype   and may PGRN mutations and is rather uncommon in C9orf72 mutations and VCP  mutations and rare in TARDP mutations cases. PSP-like features may be rarely observed in both C9orf72 and PGRN mutation carriers, CBS-like features are uncommon in PGRN and rare in C9orf72 [Akinetic–rigid parkinsonism, as far as TDP-43 proteinopathies are concerned, occurs commonly in  C9orf72 . Of note C9orf72 ,130.C9orf72 or TARDBP gene mutations, but also those with DCTN1 (Dynactin Subunit 1) and VCP gene mutations.Among inherited FTLD cases, MND is observed mainly in patients carrying DCTN1 mutation, TDP-43 pathology is predominant [In some very rare clinical entities, such as Perry disease, caused by dominant . In othedominant . In Perrdominant  are accodominant .Another example of the complex relationship between ALS and parkinsonism is the rare variant of ALS: ALS and parkinsonism/dementia complex (ALS/PDC) in which TDP-43 pathology may be accompanied by alpha-synuclein pathology. In ALS/PDC three types of pathology were described: the tauopathy-dominant type, the TDP-43 proteinopathy-dominant type, and the synucleinopathy-dominant type .C9orf72 is a relatively recently described mutation as are Strong et al.’s criteria [The frequency of parkinsonism in ALS–FTSD with TDP-43 proteinopathy cannot be easily established. Parkinsonism may be an under-diagnosed phenomenon in ALS–FTSD with TDP-43 proteinopathy due to several reasons. First, genetic testing and/or neuropathological examination is not routinely performed worldwide, remaining unproven in many cases. Secondly, In conclusion, the theme of parkinsonism in ALS–FTLD guarantees further research since at present there are a lot of gaps that need to be filled, specifically regarding parkinsonism in sporadic forms of ALS–FTSD with defined neuropathology and its clinical subgroups. Finally, it would be interesting to investigate whether parkinsonian symptoms observed in ALS–FTLD could be mediated by TDP-43-associated parkin decrease.TDP-43 related mitochondrial dysfunction has been observed in genetic and sporadic forms of TDP-43 proteinopathies and in several cellular and animal models ,135. In PARK2 by TDP-43 , TBK1 (TANK Binding Kinase 1), SQSTM1/p62, and VCP ) that cause genetic forms of ALS–FTSD with TDP-43 proteinopathy encode proteins involved in mitophagy/autophagy [In addition, a majority of genes  levels has been confirmed in Parkinson’s disease patients with utations . The lacC9orf72, PGRN, and TARDBP itself, that cause familial forms of ALS–FTSD.While it is well documented that TDP-43 pathology represents one of the main mechanisms underlying various aspects of mitochondrial dysfunction, its actions can also be modulated by different genetic backgrounds, such as mutations in In this section, we discuss sporadic ALS–FTSD cases where, apparently, TDP-43 proteinopathy is not modified by additional genetic factors.First, it is important to note that induced pluripotent stem cells (iPSCs) and postmortem samples derived from patients with sporadic ALS and FTLD have demonstrated the destabilization of ribosomal and mitochondrial transcripts with decreased levels of corresponding mitochondrial proteins, as well as altered morphology and respiration ,154. A sSecondly, transcriptomic analysis of frontal cortex in 16 patients with sporadic FTLD–TDP followed by mRNA and protein level validation has demonstrated downregulation and decreased activity of several mitochondrial subunits of electron transport chain  .The results of these functional studies are supported by ultrastructural and morphological analyses which have revealed abnormal mitochondrial and lysosomal phenotypes in brain samples derived from patients with sporadic FTLD or ALS ,156. In Finally, it has been observed that TDP-43 aggregation-driven oxidative stress in mouse and human neurons depleted mitochondrial proteins encoded by nuclear-genome, leading to global mitochondrial dysfunction oxidative stress .In conclusion, TDP-43-induced mitochondrial impairment certainly represents a critical aspect in TDP-43 proteinopathy.C9ORF72 hexanucleotide repeat expansion, TDP-43 pathology is accompanied by dipeptide repeat (DPR) protein aggregates arising from the unconventional repeat-associated non-ATG translation [C9ORF72 pathology may act through loss-of-function (C9orf72 haploinsufficiency) and gain-of-function mechanisms. The latter one is associated with the generation of long G4C2 expansions that may sequester cellular proteins from their normal functions and even generate toxic dipeptide repeat proteins [In patients with nslation ,159. Simproteins .C9ORF72 and TARDBP have shown similar effects on various mitochondrial parameters, such as increased oxidative and endoplasmic reticulum (ER) stress, impaired mitochondrial transport in axons, abnormal morphology, reduced ATP production, Ca2+ signaling, mitochondrial membrane potential, and activity of mitochondrial respiratory complexes [C9ORF72- or TARDBP-linked ALS–FTSD, Drosophila and mouse models [From a pathological point of view, ALS- and FTLD-associated mutations in omplexes ,166,167,omplexes ,140. Expe models ,171,172.Drosophila expressing TDP-43 A315T mutant [Abnormal mitochondrial phenotypes have been described in spinal motor neurons from patient-derived iPSCs with TDP43 S393L and G294V mutations , mice anT mutant ,156.Drosophila muscle and patient fibroblasts with C9ORF72 hexanucleotide repeat expansion, poly(GR) was observed to enter mitochondria and interfere with the function of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), which led to abnormal mitochondrial inner membrane structure, metabolism, and ion homeostasis [C9orf72 is crucial for effective mitochondrial complex I assembly [C9orf72 hexanucleotide repeat expansion in astrocytes deregulated metabolism of adenosine, fructose, and glycogen, and the transport of mitochondria-specific energy substrates, thus increasing toxicity upon starvation [In eostasis . In iPSCeostasis ,170. Thieostasis . In addiassembly . Finallyarvation ,174.C9ORF72 in mitochondrial complex assembly might be one of the reasons for observation of parkinsonisms in FTLD–C9ORF72 cases, since mitochondrial complex dysfunction is one of the best-documented Parkinson’s disease molecular mechanisms [In conclusion, it can therefore be speculated that the involvement of chanisms .PGRN mutations [As it has been well established in many previous studies, PGRN haploinsufficiency always leads to TDP-43 pathology ,177. Regutations . ConsideRegarding the potential role played by PGRN in mitophagy, it has been recently reported that a decrease in PGRN exacerbated mitochondrial damage and dysfunction in podocytes from diabetic mice and that PGRN administration was able to restore mitophagy and mitochondrial biogenesis in podocytes challenged with high glucose through upregulation of Sirt1-PGC-1α/FoxO1 pathway .PGRN mutations which could not be rescued by TDP-43 overexpression, suggesting that established life-long TDP-43 pathology effects cannot be simply resolved through manipulation of TDP-43 level [Finally, as described in 43 level .In summary, while the evidence on mitochondrial dysfunction in TDP-43 proteinopathies is substantial, it is not known whether TDP-43-related decrease of parkin could contribute to some of the observed mitochondrial phenotypes. To address this issue, it might be recommended that future studies on mitochondrial function in TDP-43 pathology model systems could test whether parkin is involved mechanistically, and, if yes, at which specific stage.PARK2 or PARK6 mutations, as reviewed in Reference [PARK2 mutation carrier that protected this individual from developing Parkinson’s disease even in his 80s [Mitophagy-enhancing therapies designed to increase PINK1 and parkin activity and/or inhibit ubiquitin-specific peptidase 30 (USP30) seem to be a plausible solution to rescue parkin/PINK1 deficiency in Parkinson’s disease caused by eference . Notably his 80s . The pat his 80s .Drosophila expressing h-TDP-43 in neurons [In TDP-43 proteinopathies, it has been shown that drugs increasing endogenous parkin levels were also able to decrease nuclear TDP-43 levels and prevent the neuronal loss and cognitive and motor decline in transgenic mice expressing either wild-type human TDP-43 or mutant A315T ,183,184. neurons .PGRN mutations derived from FTLD patients, even if it increased PGRN levels [While parkin upregulation could ameliorate deleterious effects of TDP-43 proteinopathy in these cases, an opposite approach—overexpression of TDP-43—could not rescue decreased parkin levels in fibroblasts with N levels . MoreoveIn contrast to precise targeting of the PINK1/parkin pathway, global mitophagy boost seems to aggravate phenotypes in TDP-43 proteinopathies. For example, in mice co-expressing TDP-43WT and mutant Q331K, rilmenidine administration induced autophagy and mitophagy, promoting accelerated nuclear TDP-43 clearance, but worsening the neurodegenerative phenotype, resulting in enhanced motor neuron death, and shortened lifespan .Finally, in some genetic forms of ALS and FTLD with elevated basal levels of autophagy ,186,187,