An Insight on Skin Cancer About Different Targets With Update on Clinical Trials and Investigational Drugs.

Cancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth.

Enhanced LiMn2O4 Thin-Film Electrode Stability in Ionic Liquid Electrolyte: A Pathway to Suppress Mn Dissolution.

Spinel-type lithium manganese oxide (LiMn2O4) cathodes suffer from severe manganese dissolution in the electrolyte, compromising the cyclic stability of LMO-based Li-ion batteries (LIBs). In addition to causing structural and morphological deterioration to the cathode, dissolved Mn ions can migrate through the electrolyte to deposit on the anode, accelerating capacity fade. Here, we examine single-crystal epitaxial LiMn2O4 (111) thin-films using synchrotron in situ X-ray diffraction and reflectivity to study the structural and interfacial evolution during cycling. Cyclic voltammetry is performed in a wide range (2.5-4.3 V vs Li/Li+) to promote Mn3+ formation, which enhances dissolution, for two different electrolyte systems: an imidazolium ionic liquid containing lithium bis-(trifluoromethylsulfonyl)imide (LiTFSI) and a conventional carbonate liquid electrolyte containing lithium hexafluorophosphate (LiPF6). We find exceptional stability in this voltage range for the ionic liquid electrolyte compared to the conventional electrolyte, which is attributed to the absence of Mn dissolution in the ionic liquid. X-ray reflectivity shows a negligible loss of cathode material for the films cycled in the ionic liquid electrolyte, further confirmed by inductively coupled plasma mass spectrometry and transmission electron microscopy. Conversely, a substantial loss of Mn is found when the film is cycled in the conventional electrolyte. These findings show the significant advantages of ionic liquids in suppressing Mn dissolution in LiMn2O4 LIB cathodes.

Exploring potential of diacerin nanogel for topical application in arthritis: Formulation development, QbD based optimization and pre-clinical evaluation.

Diacerein (DCN) is a chondroprotective agent which shows inadequate oral bioavailability along with gastrointestinal side effects. This study is intended to develop a topical novel DCN delivery system. DCN nanogel was prepared by emulsion solvent diffusion technique. The formulation was optimized by response surface methodology by taking two independent variables, concentration of carbopol 940 and eudragit RSPO and three dependent variables, particle size, % entrapment efficiency (EE) and % drug release at 24 h. The optimized formulation had adequat% EE, % drug release at 24 h and particle size. The particle size for optimized nanogel was 190.3 nm with % EE of 83.51% whereas % drug release at 24 h was found 90.13%. The optimized DCN nanogel was analyzed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (DTIR) and transmission electron microscopy (TEM) studies. The drug release kinetic study has shown that the gel followed Higuchi's model and the diffusion was anomalous in nature. The nanogel was characterized for physical examination, viscosity, homogeneity and stability parameters and the results obtained were found upto the mark. The ex-vivo permeation study data was in correlation with results of in-vitro study. In-vivo anti-arthritic study proved the efficacy of developed formulation for arthritis in Freund's Adjuvant Arthritic model. This research work has proved the significant potential of innovated product for arthritis by topical route, as it overcomes the drawbacks of oral route, highly efficient, sustained and targeted the release of drug without any accumulation and toxicity.

Comparative Study of Chemosensory Dysfunction in COVID-19 in 2 Geographically Distinct Regions.

OBJECTIVE: To directly compare the prevalence of chemosensory dysfunction (smell and taste) in geographically distinct regions with the same questionnaires. METHODS: A cross-sectional study was performed to evaluate the self-reported symptoms among adults (older than 18 years) who underwent COVID-19 testing at an ambulatory assessment center in Canada and at a hospital in Israel between March 16, 2020, and August 19, 2020. The primary outcome was the prevalence of self-reported chemosensory dysfunction (anosmia/hypomsia and dysgeusia/ageusia). Subgroup analysis was performed to evaluate the prevalence of chemosensory deficits among the outpatients. RESULTS: We identified a total of 350 COVID-19-positive patients (138 Canadians and 212 Israelis). The overall prevalence of chemosensory dysfunction was 47.1%. There was a higher proportion of chemosensory deficits among Canadians compared to Israelis (66.7% vs 34.4%, P < .01). A subgroup analysis for outpatients (never hospitalized) still identified a higher prevalence of chemosensory dysfunction among Canadians compared to Israelis (68.2% vs 36.1%, P < 0.01). A majority of patients recovered their sense of smell after 4 weeks of symptom onset. CONCLUSION: Although the prevalence of chemosensory deficit in COVID-19 was found to be similar to previously published reports, the prevalence can vary significantly across different geographical regions. Therefore, it is important to obtain regionally specific data so that the symptom of anosmia/dysgeusia can be used as a guide for screening for the clinical diagnosis of COVID-19.

Developing a Chemical and Structural Understanding of the Surface Oxide in a Niobium Superconducting Qubit.

Superconducting thin films of niobium have been extensively employed in transmon qubit architectures. Although these architectures have demonstrated improvements in recent years, further improvements in performance through materials engineering will aid in large-scale deployment. Here, we use information retrieved from secondary ion mass spectrometry and electron microscopy to conduct a detailed assessment of the surface oxide that forms in ambient conditions for transmon test qubit devices patterned from a niobium film. We observe that this oxide exhibits a varying stoichiometry with NbO and NbO2 found closer to the niobium film/oxide interface and Nb2O5 found closer to the surface. In terms of structural analysis, we find that the Nb2O5 region is semicrystalline in nature and exhibits randomly oriented grains on the order of 1-3 nm corresponding to monoclinic N-Nb2O5 that are dispersed throughout an amorphous matrix. Using fluctuation electron microscopy, we are able to map the relative crystallinity in the Nb2O5 region with nanometer spatial resolution. Through this correlative method, we observe that the highly disordered regions are more likely to contain oxygen vacancies and exhibit weaker bonds between the niobium and oxygen atoms. Based on these findings, we expect that oxygen vacancies likely serve as a decoherence mechanism in quantum systems.

Challenges faced by people experiencing homelessness and their providers during the COVID-19 pandemic: a qualitative study.

BACKGROUND: People experiencing homelessness are vulnerable to SARS-CoV-2 infection and its consequences. We aimed to understand the perspectives of people experiencing homelessness, and of the health care and shelter workers who cared for them, during the COVID-19 pandemic. METHODS: We conducted an interpretivist qualitative study in Toronto, Canada, from December 2020 to June 2021. Participants were people experiencing homelessness who received SARS-CoV-2 testing, health care workers and homeless shelter staff. We recruited participants via email, telephone or recruitment flyers. Using individual interviews conducted via telephone or video call, we explored the experiences of people who were homeless during the pandemic, their interaction with shelter and health care settings, and related system challenges. We analyzed the data using reflexive thematic analysis. RESULTS: Among 26 participants were 11 men experiencing homelessness (aged 28-68 yr), 9 health care workers (aged 33-59 yr), 4 health care leaders (aged 37-60 yr) and 2 shelter managers (aged 47-57 yr). We generated 3 main themes: navigating the unknown, wherein participants grappled with evolving public health guidelines that did not adequately account for homeless individuals; confronting placelessness, as people experiencing homelessness often had nowhere to go owing to public closures and lack of isolation options; and struggling with powerlessness, since people experiencing homelessness lacked agency in their placelessness, and health care and shelter workers lacked control in the care they could provide. INTERPRETATION: Reduced shelter capacity, public closures and lack of isolation options during the COVID-19 pandemic exacerbated the displacement of people experiencing homelessness and led to moral distress among providers. Planning for future pandemics must account for the unique needs of those experiencing homelessness.

Association of Homelessness with COVID-19 Positivity among Individuals Visiting a Testing Centre: A Cross-Sectional Study.

Among those visiting a testing centre in Toronto, ON, between March and April 2020, people experiencing homelessness (n = 214) were more likely to test positive for COVID-19 compared with those not experiencing homelessness (n = 1,836) even after adjustment for age, sex and medical co-morbidity (15.4% vs. 6.7%, p < 0.001; odds ratio [OR] 2.41, 95% confidence interval [CI: 1.51, 3.76], p < 0.001).

Computer vision AC-STEM automated image analysis for 2D nanopore applications.

Transmission electron microscopy (TEM) has led to important discoveries in atomic imaging and as an atom-by-atom fabrication tool. Using electron beams, atomic structures can be patterned, annealed and crystallized, and nanopores can be drilled in thin membranes. We review current progress in TEM analysis and implement a computer vision nanopore-detection algorithm that achieves a 96% pixelwise precision in TEM images of nanopores in 2D membranes (WS2), and discuss parameter optimization including a variation on the traditional grid search and gradient ascent. Such nanopores have applications in ion detection, water filtration, and DNA sequencing, where ionic conductance through the pore should be concordant with its TEM-measured size. Standard computer vision methods have their advantages as they are intuitive and do not require extensive training data. For completeness, we briefly comment on related machine learning for 2D materials analysis and discuss relevant progress in these fields. Image analysis alongside TEM allows correlated fabrication and analysis done simultaneously in situ to engineer devices at the atomic scale.

Factors associated with SARS-CoV-2 positivity in 20 homeless shelters in Toronto, Canada, from April to July 2020: a repeated cross-sectional study.

BACKGROUND: It is unclear what the best strategy is for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among residents of homeless shelters and what individual factors are associated with testing positive for the virus. We sought to evaluate factors associated with testing positive for SARS-CoV-2 among residents of homeless shelters and to evaluate positivity rates in shelters where testing was conducted in response to coronavirus disease 2019 (COVID-19) outbreaks or for surveillance. METHODS: We conducted a retrospective chart audit to obtain repeated cross-sectional data from outreach testing done at homeless shelters between Apr. 1 and July 31, 2020, in Toronto, Ontario, Canada. We compared the SARS-CoV-2 positivity rate for shelters where testing was conducted because of an outbreak (at least 1 known case) with those tested for surveillance (no known cases). A patient-level analysis evaluated differences in demographic, health and behavioural characteristics of residents who did and did not test positive for SARS-CoV-2 at shelters with at least 2 positive cases. RESULTS: One thousand nasopharyngeal swabs were done on 872 unique residents at 20 shelter locations. Among the 504 tests done in outbreak settings, 69 (14%) were positive for SARS-CoV-2 and 1 (0.2%) was indeterminate. Among the 496 tests done for surveillance, 11 (2%) were positive and none were indeterminate. Shelter residents who tested positive for SARS-CoV-2 were significantly less likely to have a health insurance card (54% v. 72%, p = 0.03) or to have visited another shelter in the last 14 days (0% v. 18%, p < 0.01). There was no association between SARS-CoV-2 positivity and medical history or symptoms. INTERPRETATION: Our findings support testing of asymptomatic shelter residents for SARS-CoV-2 when a positive case is identified at the same shelter. Surveillance testing when there are no known positive cases may detect outbreaks, but further research should identify efficient strategies given scarce testing resources.

Rapid Growth of Monolayer MoSe2 Films for Large-Area Electronics.

The large-scale growth of semiconducting thin films on insulating substrates enables batch fabrication of atomically thin electronic and optoelectronic devices and circuits without film transfer. Here an efficient method to achieve rapid growth of large-area monolayer MoSe2 films based on spin coating of Mo precursor and assisted by NaCl is reported. Uniform monolayer MoSe2 films up to a few inches in size are obtained within a short growth time of 5 min. The as-grown monolayer MoSe2 films are of high quality with large grain size (up to 120 µm). Arrays of field-effect transistors are fabricated from the MoSe2 films through a photolithographic process; the devices exhibit high carrier mobility of ≈27.6 cm2 V-1 s-1 and on/off ratios of ≈105. The findings provide insight into the batch production of uniform thin transition metal dichalcogenide films and promote their large-scale applications.

Gas flow through atomic-scale apertures.

Gas flows are often analyzed with the theoretical descriptions formulated over a century ago and constantly challenged by the emerging architectures of narrow channels, slits, and apertures. Here, we report atomic-scale defects in two-dimensional (2D) materials as apertures for gas flows at the ultimate quasi-0D atomic limit. We establish that pristine monolayer tungsten disulfide (WS2) membranes act as atomically thin barriers to gas transport. Atomic vacancies from missing tungsten (W) sites are made in freestanding (WS2) monolayers by focused ion beam irradiation and characterized using aberration-corrected transmission electron microscopy. WS2 monolayers with atomic apertures are mechanically sturdy and showed fast helium flow. We propose a simple yet robust method for confirming the formation of atomic apertures over large areas using gas flows, an essential step for pursuing their prospective applications in various domains including molecular separation, single quantum emitters, sensing and monitoring of gases at ultralow concentrations.

Stochastic Ionic Transport in Single Atomic Zero-Dimensional Pores.

We report on single atomic zero-dimensional (0D) pores fabricated using aberration-corrected scanning transmission electron microscopy (AC-STEM) in monolayer MoS2. Pores are comprised of a few atoms missing in the two-dimensional (2D) lattice (1-5 Mo atoms) of characteristic sizes from ∼0.5 to 1.2 nm, and pore edges directly probed by AC-STEM to map the atomic structure. We categorize them into ∼30 geometrically possible zigzag, armchair, and mixed configurations. While theoretical studies predict that transport properties of 2D pores in this size range depend strongly on pore size and their atomic configuration, 0D pores show an average conductance in the range from ∼0.6-1 nS (bias up to 0.1 V), similar to biological pores. In some devices, the current was immeasurably small and/or pores could not be wet. Furthermore, current-voltage (I-V) characteristics are largely independent of bulk molarity (10 mM to 3 M KCl) and the type of cation (K+, Li+, Mg2+). This work lays the experimental foundation for understanding of the confinement effects possible in atomic-scale 2D material pores and the realization of solid-state analogues of ion channels in biology.

Spatial defects nanoengineering for bipolar conductivity in MoS2.

Understanding the atomistic origin of defects in two-dimensional transition metal dichalcogenides, their impact on the electronic properties, and how to control them is critical for future electronics and optoelectronics. Here, we demonstrate the integration of thermochemical scanning probe lithography (tc-SPL) with a flow-through reactive gas cell to achieve nanoscale control of defects in monolayer MoS2. The tc-SPL produced defects can present either p- or n-type doping on demand, depending on the used gasses, allowing the realization of field effect transistors, and p-n junctions with precise sub-µm spatial control, and a rectification ratio of over 104. Doping and defects formation are elucidated by means of X-Ray photoelectron spectroscopy, scanning transmission electron microscopy, and density functional theory. We find that p-type doping in HCl/H2O atmosphere is related to the rearrangement of sulfur atoms, and the formation of protruding covalent S-S bonds on the surface. Alternatively, local heating MoS2 in N2 produces n-character.

Self-reported anosmia and dysgeusia as key symptoms of coronavirus disease 2019.

OBJECTIVES: To slow down the transmission of coronavirus disease 2019 (COVID-19), it is important to identify specific symptoms for effective screening. While anosmia/hyposmia and dysgeusia/ageusia have been identified as highly prevalent symptoms, there are wide geographic variations, necessitating the regional evaluation of the prevalence of the symptoms. METHODS: A cross-sectional study was performed to evaluate the self-reported symptoms among adults (over 18 years old) who underwent COVID-19 tests at an ambulatory assessment centre. We identified 1,345 patients (102 positive and 1,243 negative) who visited the assessment centre between March 16 and April 15, 2020. We randomly sampled negative patients in a 1:3 ratio. The primary outcome was the prevalence of self-reported anosmia/hyposmia and dysgeusia/ageusia. Logistic regression was performed to evaluate the association between COVID-19 positivity and loss of smell and taste. RESULTS: Fifty-six of 102 (50%) positive patients and 72 of 306 (23.5%) negative patients completed the survey. Anosmia/hyposmia and dysgeusia/ageusia were more prevalent among COVID-19 positive patients (41.1% v. 4.2%, p < 0.001 for smell and 46.4% v. 5.6%, p < 0.001 for taste). Anosmia/hyposmia and dysgeusia/ageusia were independently highly associated with COVID-19 positivity (adjusted odds ratios 14.4 and 11.4 for smell and taste, respectively). CONCLUSION: In this Canadian study, smell and taste loss may be key symptoms of COVID-19. This evidence can be helpful in the clinical diagnosis of COVID-19, particularly settings of limited testing capacity.

In Situ 2D MoS2 Field-Effect Transistors with an Electron Beam Gate.

We use the beam of a transmission electron microscope (TEM) to modulate in situ the current-voltage characteristics of a two-terminal monolayer molybdenum disulfide (MoS2) channel fabricated on a silicon nitride substrate. Suppression of the two-dimensional (2D) MoS2 channel conductance up to 94% is observed when the beam hits and charges the substrate surface. Gate-tunable transistor characteristics dependent on beam current are observed even when the beam is up to tens of microns away from the channel. In contrast, conductance remains constant when the beam passes through a micron-sized hole in the substrate. There is no MoS2 structural damage during gating, and the conductance reverts to its original value when the beam is turned off. We observe on/off ratios up to ∼60 that are largely independent of beam size and channel length. This TEM field-effect transistor architecture with electron beam gating provides a platform for future in situ electrical measurements.

Lifetime and Stability of Silicon Nitride Nanopores and Nanopore Arrays for Ionic Measurements.

Nanopores are promising for many applications including DNA sequencing and molecular filtration. Solid-state nanopores are preferable over their biological counterparts for applications requiring durability and operation under a wider range of external parameters, yet few studies have focused on optimizing their robustness. We report the lifetime and durability of pores and porous arrays in 10 to 100 nm-thick, low-stress silicon nitride (SiNx) membranes. Pores are fabricated using a transmission electron microscope (TEM) and/or electron beam lithography (EBL) and reactive ion etching (RIE), with diameters from 2 to 80 nm. We store them in various electrolyte solutions (KCl, LiCl, MgCl2) and record open pore conductance over months to quantify pore stability. Pore diameters increase with time, and diameter etch rate increases with electrolyte concentration from Δd/Δt ∼ 0.2 to ∼ 3 nm/day for 0.01 to 3 M KCl, respectively. TEM confirms the range of diameter etch rates from ionic measurements. Using electron energy loss spectroscopy (EELS), we observe a N-deficient region around the edges of TEM-drilled pores. Pore expansion is caused by etching of the Si/SiO2 pore walls, which resembles the dissolution of silicon found in minerals such as silica (SiO2) in salty ocean water. The etching process occurs where the membrane was exposed to the electron beam and can result in pore formation. However, coating pores with a conformal 1 nm-thick hafnium oxide layer prevents expansion in 1 M KCl, in stark contrast to bare SiNx pores (∼ 1.7 nm/day). EELS data reveal the atomic composition of bare and HfO2-coated pores.

Ions and Water Dancing through Atom-Scale Holes: A Perspective toward "Size Zero".

We provide an overview of atom-scale apertures in solid-state membranes, from "pores" and "tubes" to "channels", with characteristic sizes comparable to the sizes of ions and water molecules. In this regime of ∼1 nm diameter pores, water molecules and ions are strongly geometrically confined: the size of water molecules (∼0.3 nm) and the size of "hydrated" ions in water (∼0.7-1 nm) are similar to the pore diameters, physically limiting the ion flow through the hole. The pore sizes are comparable to the classical Debye screening length governing the spatial range of electrostatic interaction, ∼0.3 to 1 nm for 1 to 0.1 M KCl. In such small structures, charges can be unscreened, leading to new effects. We discuss experiments on ∼1 nm diameter nanopores, with a focus on carbon nanotube pores and ion transport studies. Finally, we present an outlook for artificial "size zero" pores in the regime of small diameters and small thicknesses. Beyond mimicking protein channels in nature, solid-state pores may offer additional possibilities where sensing and control are performed at the pore, such as in electrically and optically addressable solid-state materials.

Atomic-scale patterning in two-dimensional van der Waals superlattices.

Two-dimensional (2D) van der Waals superlattices comprised of two stacked monolayer materials have attracted significant interest as platforms for novel optoelectronic and structural behavior. Although studies are focused on superlattice fabrication, less effort has been given to the nanoscale patterning and structural modification of these systems. In this report, we demonstrate the localized layer-by-layer thinning and formation of nanopores/defects in 2D superlattices, such as stacked MoS2-WS2 van der Waals heterostructures and chemical vapor deposited bilayer WSe2, using aberration-corrected scanning transmission electron microscopy (STEM). Controlled electron beam irradiation is used to locally thin superlattices by removing the bottom layer of atoms, followed by defect formation through ablation of the second layer of atoms. The resulting defects exhibit atomically-sharp pore edges with tunable diameters down to 0.6 nm. Structural periodicities and focused STEM irradiation are also utilized to form close-packed nanopore arrays in superlattices with varying twist angles and commensurability. Applying these methods and mechanisms provides a forward approach in the atomic-scale patterning of stacked 2D nanodevices.

Controlled Growth of Large-Area Bilayer Tungsten Diselenides with Lateral P-N Junctions.

Bilayer two-dimensional (2D) van der Waals (vdW) materials are attracting increasing attention due to their predicted high quality electronic and optical properties. Here, we demonstrate dense, selective growth of WSe2 bilayer flakes by chemical vapor deposition with the use of a 1:10 molar mixture of sodium cholate and sodium chloride as the growth promoter to control the local diffusion of W-containing species. A large fraction of the bilayer WSe2 flakes showed a 0 (AB) and 60° (AA') twist between the two layers, whereas Moiré 15 and 30° twist angles were also observed. Well-defined monolayer-bilayer junctions were formed in the as-grown bilayer WSe2 flakes, and these interfaces exhibited p-n diode rectification and an ambipolar transport characteristic. This work provides an efficient method for the layer-controlled growth of 2D materials, in particular, 2D transition metal dichalcogenides, and promotes their applications in next-generation electronic and optoelectronic devices.