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Abstract HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Abstract Background Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinonasal tract. To understand this disease entity and develop targeted treatments, a reproducible animal model is paramount. Aims/objectives To optimize a murine model of eosinophilic CRS by establishing benchmark histological markers and validate its fidelity in evaluating intranasal treatments. Material and methods Forty-five Balb/c mice were included in the 7-week protocol. Experimental animals (n = 20) were induced a CRS disease state upon receiving intraperitoneal sensitization with ovalbumin (OVA), followed by intranasal OVA with Aspergillus oryzae protease. Analysis of complete blood count with differential, peripheral blood smear, and histological markers from the nasal cavity mucosa were performed. CRS mice were additionally treated with intranasal saline (n = 5) or mometasone (n = 10) and compared with control groups of untreated CRS (n = 5) and healthy (n = 5) mice after week 7. Results Histological analysis of experimental animal nasal mucosa revealed significantly higher levels of eosinophilic tissue infiltration/degranulation, hyaline droplets, Charcot–Leyden crystals, and respiratory epithelial thickness compared to healthy controls. Treatment with mometasone significantly reversed the histopathological changes observed in CRS mice. Conclusion and significance This murine model induced substantial local eosinophilic inflammation within sinonasal mucosa, that was reversible with mometasone. This model may be used to evaluate the efficacy of therapeutics designed to target CRS.

The nuclear factor E2-related factor 1 (Nrf1) transcription factor performs a critical role in regulating cellular homeostasis as part of the cellular stress response and drives the expression of antioxidants and detoxification enzymes among many other functions. Ubiquitination plays an important role in controlling the abundance and thus nuclear accumulation of Nrf1 proteins, but the regulatory enzymes that act on Nrf1 are not fully defined. Here, we identified ubiquitin specific protease 7 (USP7), a deubiquitinating enzyme, as a novel regulator of Nrf1 activity. We found that USP7 interacts with Nrf1a and TCF11-the two long protein isoforms of Nrf1. Expression of wildtype USP7, but not its catalytically defective mutant, resulted in decreased ubiquitination of TCF11 and Nrf1a, leading to their increased stability and increased transactivation of reporter gene expression by TCF11 and Nrf1a. In contrast, knockdown or pharmacologic inhibition of USP7 dramatically increased ubiquitination of TCF11 and Nrf1a and reduction of their steady state levels. Loss of USP7 function attenuated the induction of Nrf1 protein expression in response to treatment with arsenic and other toxic metals, and inhibition of USP7 activity significantly sensitized cells to arsenic treatment. Collectively, these findings suggest that USP7 may act to modulate abundance of Nrf1 protein to induce gene expression in response to toxic metal exposure.

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes. Head and neck squamous cell carcinoma can occur with and without the presence of HPV infection. Here, the authors utilise Mendelian randomization to assess the causal effects of smoking and alcohol on HPV-positive and HPV-negative head and neck cancer development. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. Methods: This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. Results: A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P =.003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P =.01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P =.001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P =.006] were each independently associated with increased odds of ototoxicity. Conclusions: Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity. [ABSTRACT FROM AUTHOR]

Developing future electronics will require aggressive scaling of the channel material thickness while maintaining device performance. Two-dimensional (2D) semiconductors are promising candidates to sustain further device scaling, but despite more than two decades of intense research, experimental performance continues to lag theoretical expectations. Here, we develop an oxygen-free approach to fabricate 2D field-effect transistors and push the electrical transport toward the theoretical phonon-limited intrinsic mobility. This approach achieves record carrier mobilities of 91 and 132 cm 2 V -1 s -1 for mono- and bilayer MoS 2 transistors on silicon oxide substrates. Statistical analysis of over 60 MoS 2 and WS 2 devices confirms that oxygen-free fabrication enhances device performance by more than an order of magnitude across key figures of merit. While previous studies suggest that 2D transition metal dichalcogenides such as MoS 2 and WS 2 are relatively stable in air, we show that even short-term ambient exposure can degrade their performance. We identify oxygen as a crucial factor in limiting transistor performance through irreversible chemisorption. This study emphasizes the criticality of avoiding oxygen exposure and offers guidance for device manufacturing that impacts fundamental research and practical applications of 2D materials.

In this study, molecular beam epitaxial growth of strain-driven three-dimensional self-assembled Ge/GeSi islands on silicon-on-insulator (SOI) substrates, along with their optical and photodetection characteristics, have been demonstrated. The as-grown islands exhibit a bimodal size distribution, consisting of both Ge and GeSi alloy islands, and show significant photoluminescence (PL) emission at room temperature, specifically near optical communication wavelengths. Additionally, these samples were used to fabricate a Ge/GeSi islands/Si nanowire based phototransistor using a typical e-beam lithography process. The fabricated device exhibited broadband photoresponse characteristics, spanning a wide wavelength range (300-1600 nm) coupled with superior photodetection characteristics and relatively low dark current (∼ tens of pA). The remarkable photoresponsivity of the fabricated device, with a peak value of ∼11.4 A W -1 ( λ ∼ 900 nm) in the near-infrared region and ∼1.36 A W -1 ( λ ∼ 1500 nm) in the short-wave infrared (SWIR) region, is a direct result of the photoconductive gain exceeding unity. The room-temperature optical emission and outstanding photodetection performance, covering a wide spectral range from the visible to the SWIR region, showcased by the single layer of Ge/GeSi islands on SOI substrate, highlight their potential towards advanced applications in broadband infrared Si-photonics and imaging. These capabilities make them highly promising for cutting-edge applications compatible with complementary metal-oxide-semiconductor technology., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Assembling two-dimensional van der Waals (vdW)-layered materials into heterostructures is an exciting development that sparked the discovery of rich correlated electronic phenomena. vdW heterostructures also offer possibilities for designer device applications in areas such as optoelectronics, valley- and spintronics, and quantum technology. However, realizing the full potential of these heterostructures requires interfaces with exceptionally low disorder which is challenging to engineer. Here, we show that thermal scanning probes can be used to create pristine interfaces in vdW heterostructures. Our approach is compatible at both the material- and device levels, and monolayer WS 2 transistors show up to an order of magnitude improvement in electrical performance from this technique. We also demonstrate vdW heterostructures with low interface disorder enabling the electrical formation and control of quantum dots that can be tuned from macroscopic current flow to the single-electron tunneling regime.

The family of 2-dimensional (2D) semiconductors is a subject of intensive scientific research due to their potential in next-generation electronics. While offering many unique properties like atomic thickness and chemically inert surfaces, the integration of 2D semiconductors with conventional dielectric materials is challenging. The charge traps at the semiconductor/dielectric interface are among many issues to be addressed before these materials can be of industrial relevance. Conventional electrical characterization methods remain inadequate to quantify the traps at the 2D semiconductor/dielectric interface since the estimations of the density of interface traps, D it , by different techniques may yield more than an order-of-magnitude discrepancy, even when extracted from the same device. Therefore, the challenge to quantify D it at the 2D semiconductor/dielectric interface is about finding an accurate and reliable measurement method. In this review, we discuss characterization techniques which have been used to study the 2D semiconductor/dielectric interface. Specifically, we discuss the methods based on small-signal AC measurements, subthreshold slope measurements and low-frequency noise measurements. While these approaches were developed for silicon-based technology, 2D semiconductor devices possess a set of unique challenges requiring a careful re-evaluation when using these characterization techniques. We examine the conventional methods based on their efficacy and accuracy in differentiating various types of trap states and provide guidance to find an appropriate method for charge trap analysis and estimation of D it at 2D semiconductor/dielectric interfaces.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation 1,2 . Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid 1-3 . A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation 1 . NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft 4 . Although past missions have utilized impactors to investigate the properties of small bodies 5,6 , those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos 7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary., (© 2023. The Author(s).)

Integration of nanolayered metal chalcogenides with wide-bandgap semiconductors forming pn heterojunction leads to the way of high-performance photodetection. This work demonstrates the fabrication of a few nanometer thick Molybdenum diselenide (MoSe 2 )/Mg-doped Gallium Nitride (p-GaN) heterostructure for light detection purposes. The device exhibits low noise broadband spectral response from ultraviolet to near-infrared range (300-950 nm). The band-alignment and the charge transfer at the MoSe 2 /p-GaN interface promote self-powered photodetection with high photocurrent to dark current ratio of 2000 and 1000 at 365 nm and 640 nm, respectively. A high responsivity of 130 A W -1 , detectivity of 4.8 × 10 10 Jones, and low noise equivalent power of 18 fW/Hz 1/2 at 365 nm is achieved at an applied bias of 1 V. Moreover, the transient measurements reveal a fast rise/fall time of 407/710 μ sec for the fabricated device. These outcomes exemplify the viability of MoSe 2 /p-GaN heterostructure for high-speed and low-noise broadband photodetector applications., (© 2022 IOP Publishing Ltd.)

A CMOS-compatible infrared (IR; 1200-1700 nm) detector based on Ge quantum dots (QDs) decorated on a single Si-nanowire channel on a silicon-on-insulator (SOI) platform with a superior detectivity at room temperature is presented. The spectral response of a single nanowire device measured in a back-gated field-effect transistor geometry displays a very high value of peak detectivity ∼9.33 × 10 11 Jones at ∼1500 nm with a relatively low dark current (∼20 pA), which is attributed to the fully depleted Si nanowire channel on SOI substrates. The noise power spectrum of the devices exhibits a1/fγ,with the exponent, γ showing two different values of 0.9 and 1.8 owing to mobility fluctuations and generation-recombination of carriers, respectively. Ge QD-decorated nanowire devices exhibit a novel polarization anisotropy with a remarkably high photoconductive gain of ∼10 4 . The superior performance of a Ge QDs/Si nanowire phototransistor in IR wavelengths is potentially attractive to integrate electro-optical devices into Si for on-chip optical communications., (© 2021 IOP Publishing Ltd.)

Transition metal dichalcogenides (TMDs) and their heterojunctions are drawing immense research interest for various applications including infrared detection. They are being studied with different semiconductor materials to explore their heterojunction properties. In this regard, we report a MoSe 2 /Si heterojunction broadband photodiode which is highly sensitive for a wide spectral range from 405 nm to 2500 nm wavelength with the maximum responsivity of ∼522 mA W -1 for 1100 nm of incident light. The hydrothermal synthesis approach leads to the imperfect growth of the MoSe 2 , creating defects in the lattice, which was confirmed by x-ray photo-spectroscopy. These sub-bandgap defects caused high optical absorption of the SWIR light as observed in the absorption spectra. The speed of the device ranges to 18/10 μs for 10 kHz modulated light. Furthermore, the photodetector has been fully operational even at zero bias voltage, making it a potential contender for self-powered photodetection.

Photo-excitation of certain semiconductors can lead to the production of reactive oxygen species that can inactivate microorganisms. The mechanisms involved are reviewed, along with two important applications. The first is the use of photocatalysis to enhance the solar disinfection of water. It is estimated that 750 million people do not have accessed to an improved source for drinking and many more rely on sources that are not safe. If one can utilize photocatalysis to enhance the solar disinfection of water and provide an inexpensive, simple method of water disinfection, then it could help reduce the risk of waterborne disease. The second application is the use of photocatalytic coatings to combat healthcare associated infections. Two challenges are considered, i.e., the use of photocatalytic coatings to give "self-disinfecting" surfaces to reduce the risk of transmission of infection via environmental surfaces, and the use of photocatalytic coatings for the decontamination and disinfection of medical devices. In the final section, the development of novel photocatalytic materials for use in disinfection applications is reviewed, taking account of materials, developed for other photocatalytic applications, but which may be transferable for disinfection purposes.