bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel analytical method for determination of diode parameters from the dark forward I–V characteristics of a silicon solar cell
Authors: Kumar Abhishek , Singh S N , Jyoti  , Tomer Shweta , Vandana  , Srivastava Sanjay Kumar , Dutta Mrinal , Pathi Prathap
Published: July 2023

A new analytical method for determining all diode parameters using dark I–V characteristics of a silicon solar cell is presented. This method has an advantage because the low- and high-voltage regions of the dark forward I–V characteristics of silicon solar cells can be described accurately by single-diode model, and only for the middle voltage region that the double-diode model may need to be applied. In view of this, a new methodology for the determination of series resistance Rs has been presented in this work, which uses only I, V values of four nearby points in high-voltage region of the dark forward I–V characteristics and does not require knowledge of any other diode parameters. Applying the single- and double-diode models, the methodologies for determination of reverse saturation currents and ideality factors (I0, n for single diode model) and (I01, n1 and I02, n2 for the double diode model) have been described. The present method of measurement of the diode parameters was applied to three silicon solar cells. Theoretical I–V curves generated using so determined values of diode parameters (Rs, Rsh, I01, n1 and I02, n2) matched excellently well with the experimental I–V characteristics of the cells obtained under dark conditions and under simulated AM1.5 G solar radiation up to 50 mW cm−2 intensity. We found that for higher intensities of illumination, while all other parameters remain constant, the value of I01, which is a representative parameter of bulk recombination, is slightly decreased with the increase in intensity.
High-performance polarization-controlled perfect optical vortex generation via all-dielectric metasurfaces in the visible region
Authors: Wang Xiaosai , Wu Jinlei , Ren Bin , Yao Jiabao , Tang Shuai , Lü Cheng , Jiang Yongyuan
Published: July 2023

Metasurfaces, with superiority in integration and flexibility compared to conventional bulky optical elements, open a perspective in generating perfect optical vortex (POV). However, the generation of POV beams with simultaneous high-efficiency, multi-functionality, and broadband is still challenging. Here, we design POV generators based on highly efficient all-dielectric metasurfaces and produce POV beams in simulation in the visible region with maximum generation efficiency of 74%. Such high efficiency originates from the stimulation of the resonance modes of polarization-dependent parity in the well-designed unit cell. By superposing two sets of phase profiles, polarization-controlled POV generators are obtained. Furthermore, the POV generator exhibits broadband property due to the geometric phase independent of the incident wavelengths. Our work provides an effective approach for generating controllable POV beams, promoting the construction of integrated and multi-functional optical systems.
Coupled chaotic vibration during pressure detection of micro-resonant pressure sensor
Authors: Fu Xiaorui , Hou Dezhi , Shi Xufei
Published: July 2023

In measuring gas pressure, the stiffness of the resonator changes in the micro-resonant pressure sensor. If the design parameters are not chosen correctly, significant variations in vibration, even chaotic vibrations, will occur in the process of gas pressure detection, seriously degrading the detection accuracy and the stability of the sensor. The micro-resonant pressure sensor is in an environment of deep coupling and mutual influence of multiple physical fields when measuring the external environmental pressure. In this work, a multi-field coupling nonlinear vibration model of the resonant sensor used in pressure detection is established, and the multi-field coupling bifurcation, chaos, and other complex vibration characteristics of the sensor system are explored. The influence of the initial gap, the length of the resonator, and the excitation voltage during pressure detection are analyzed, and the stable vibration range of each influencing parameter is determined. The results show that when the sensor measures the pressure, the initial gap of the sensor, the length of the resonator, and the stability of the excitation voltage all decrease, causing unstable vibration of the sensor. In order to obtain stable sensor detection performance, it is necessary to determine the stability range of sensor-related parameters correctly.
A massive gauge theory à la Utiyama
Authors: Cuzinatto R R , Pimentel B M , Pompeia P J , Sumire Esquia J C
Published: July 2023

Utiyama’s method is a deductive approach of building gauge theories for semi-simple groups of local transformations, including the Abelian U(1) case, the non-Abelian SU(N) group, and the gravitational interaction. Gauge theories à la Utiyama typically predict a massless gauge potential. This work brings a mass generation mechanism and Utiyama’s method together thus giving mass to the interaction boson without breaking the gauge symmetry. Herein we devote our attention to the Abelian case. Two gauge potentials are introduced: a vetor field A

μ
and a scalar field B. The associated gauge-invariant field strengths F

μ
ν
and G

μ
are built from Utiyama’s technique. Gauge invariance requirement upon the total Lagrangian (including matter fields and gauge fields) yields the conserved currents. Finally, we study the simplest type of Lagrangian involving the field strengths and obtain the related field equation. By imposing appropriate constraints on this particular example, Stueckelberg model is recovered.
Surfactant-mediated modulation of morphology and charge transfer dynamics in tungsten oxide nanoparticles
Authors: Kumar Tarun , Shreya  , Phogat Peeyush , Sahgal Vardaan , Jha Ranjana
Published: July 2023

Tungsten Oxide (WO3) is a well-known transition metal oxide which exhibits non-toxicity and stability in its nanoparticle form. It is a potential candidate for a variety of applications due to its low cost and facile synthesis process. In the present work, WO3 nanoparticles were synthesized via facile acid-coprecipitation method to explore the effect of surfactants on the morphology of WO3 nanoparticles and thus, on its structural, optical and electrochemical properties. The morphology analysis revealed the formation of spherical nanoparticles in the absence of any surfactant while nanoflakes and nanosheets were observed in the presence of cetyltrimethylammonium bromide (CTAB) and polyethylene glycol (PEG), respectively. Moreover, the presence of surfactants was found to influence the crystallinity state of the samples. The different morphologies exhibited optical band gap of 2.2–2.7 eV as analyzed by UV–vis spectroscopy along with other optical properties like absorbance range and refractive index. The electrochemical properties of the samples were studied by employing potentio electrochemical impedance spectroscopy (PEIS) and cyclic voltammetry (CV) techniques. CV analysis revealed the diffusion-controlled behavior of the samples which may be suitable for photovoltaic applications. Furthermore, impedance study showed the presence of Warburg impedance which indicates that there is an infinite layer of excitons on the surface of thin film, further suggesting WO3 as a prominent material for solar cell applications. The incorporation of surfactants resulted in the reduction of charge transfer resistance indicating more efficient charge transfer process.
Optical solitons for the Biswas-Milovic equation with anti-cubic law nonlinearity in the presence of spatio-temporal dispersion
Authors: Ozdemir Neslihan
Published: July 2023

For the first time, the optical soliton solutions of the (1 + 1)-dimensional Biswas-Milovic equation with anti-cubic law nonlinearity in the presence of spatio-temporal dispersion are intended to be analyzed in detail. To attain this purpose, the new Kudryashov and the Kudryashov auxiliary equation technique are successfully implemented. Moreover, the impacts of model parameters on the soliton dynamics are scrutinized. The complex wave transformation is utilized to get the nonlinear ordinary differential equation form and to generate soliton solutions, the presented methods are performed. Finally, various graphical illustrations were derived and detailed comments were added on the solution results. The new Kudryashov approach and the Kudryashov auxiliary equation technique have been successfully performed and soliton solutions obtained. W-shape soliton was acquired with the new Kudryashov approach and the bright soliton was acquired with the Kudryashov auxiliary equation technique. Furthermore, diverse graphic descriptions that the resulting soliton solutions are obtained, and 2D graphs are presented and commented on. Since the Biswas-Milovic equation, which is the subject of much research, has an important role in nonlinear optics, different forms of the Biswas-Milovic equation are developed in the literature. The model in the presence of spatio-temporal dispersion was presented and scrutinized for the first time.
Born-Infeld boson stars
Authors: Jaramillo Víctor , Martínez-Carbajal Daniel , Degollado Juan Carlos , Núñez Darío
Published: July 2023

We study the Einstein-Klein-Gordon system coupled to the Born-Infeld electrodynamics. We
explore the solution space of a static spherically symmetric, complex scalar field minimally
coupled to both gravitational and electromagnetic fields. The resulting asymptotically flat
solutions resemble the known charged boson stars in Maxwell electrodynamics. The behaviour of
such configurations as a function of the Born-Infeld parameter b and the scalar field charge
parameter q has been analyzed. Given b, a critical value for q exists beyond which no
static solutions exist, we find that the value of this critical charge increases with respect to
the Maxwell case (b → ∞) as b decreases. We also found that Born-Infeld boson stars have
lower mass for any finite value of the Born-Infeld parameter and that their compactness is lower
than Maxwell's counterparts.
Scalar field dark matter and dark energy: a hybrid model for the dark sector
Authors: van de Bruck Carsten , Poulot Gaspard , Teixeira Elsa M.
Published: July 2023

Diverse cosmological and astrophysical observations strongly hint at the presence of dark matter and dark energy in the Universe. One of the main goals of Cosmology is to explain the nature of these two components. It may well be that both dark matter and dark energy have a common origin. In this paper, we develop a model in which the dark sector arises due to an interplay between two interacting scalar fields. Employing a hybrid inflation potential, we show that the model can be described as a system of a pressureless fluid coupled to a light scalar field. We discuss this setup's cosmological consequences and the observational signatures in the cosmic microwave background radiation and the large-scale structures.
Security of entanglement-based QKD with realistic parametric down-conversion sources
Authors: Kravtsov K S
Published: July 2023

The paper analyzes security aspects of practical entanglement-based quantum key distribution (QKD), namely, BBM92 or entanglement-based BB84 protocol. Similar to prepare-and-measure QKD protocols, practical implementations of the entanglement-based QKD have to rely upon non-ideal photon sources. A typical solution for entanglement generation is the spontaneous parametric down-conversion. However, this process creates not only single photon pairs, but also quantum states with more than two photons, which potentially may lead to security deterioration. We show that this effect does not impair the security of entanglement-based QKD systems. We also review the available security proofs and show that properties of the entanglement source have nothing to do with security degradation.
Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration
Authors: Bryson Noah , Lombardi Lorenzo , Hawthorn Rachel , Fei Jie , Keesey Rodolfo , Peiffer J D , Seáñez Ismael
Published: July 2023

Objective. Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation. Approach. In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS. Results. Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode’s position. Significance. Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.
Modern scientific achievements in the production of agricultural organic products
Authors: Chupina I P , Ruchkin A V , Zhuravleva L A , Zarubina E V , Simachkova N N
Published: July 2023

Organic farming is not a 21st century fashion trend. As early as the beginning of the 20th century, some scientists began to treat soil fertility with understanding. Already in the seventies of the 20th century, the negative effects of chemicals were identified when they were added to the soil. It was at this time that the European Union introduced a ban on these fertilizers and in the 1980s, organic agricultural production gradually began to develop. Regulatory conditions for the production, processing and labeling of products began to be developed. Gradually, the same conditions are being developed for the forage base. By 2016, more than 180 countries have already begun to produce organic products, of which 93 countries have their own legislation and standards that regulate the production of organic products. The essence of organic products is that a person should receive a complete diet based on the principles of health. And for this, the products must be environmentally friendly and not have various chemical additives and dyes. Such products are mainly typical for farms. Large-scale production contributes to the production of environmentally friendly products to a lesser extent. In recent years, the market for organic products has been growing. The leaders in production are the USA and EU countries. Organic production is products of plant and animal origin. Basically, for organic production in large volumes, land is allocated for grain, oilseeds and legumes. Next come fresh fruits and vegetables. Such products also include wild plants, which include nuts, medicinal plants, mushrooms and wild berries. Cotton is also among the organic products. The largest cotton producers are Turkey, Tajikistan and Kyrgyzstan. Each individual country has developed a line of organic products that it can produce according to climatic conditions and its capabilities. For example, for Russia there are all opportunities for the production of wild plants, which require minimal investment, and the climatic conditions allow the country to become one of the leading producers of this product in the future.
Organic food as estimated by young consumers
Authors: Zhuravleva L A , Zarubina E V , Ruchkin A V , Chupina I P , Simachkova N N
Published: July 2023

The article analyzes the data obtained during a sociological study conducted in September-November 2022 on the analysis of the food market of agricultural organic products (on the example of the Sverdlovsk region).” The hypothesis of the connection of consumer preferences with the current ecological position and understanding of the importance of socially responsible behavior was confirmed. The key needs of young consumers that determine the choice of organic food products and their connection with the attitude to maintaining and strengthening health for a bright and interesting life are identified. The authors recorded the reasons for the respondents’ refusal to purchase organic products and the sensitivity of consumers to the increased cost of organic food products. The conclusion is made about the different patterns of consumer behavior of respondents in the segments of the organic food market and their connection with the dominant values and established eating habits. Three styles of consumer behavior are described: ecological, stereotypical, unstable. The ecological style is characterized by attitudes towards the use of healthy and environmentally friendly foods as factors in maintaining an active lifestyle and health. The stereotypical style of eating is characterized by: a strong influence of the environment on the choice of food and diet, low reflection on their own food practices, lack of sufficient knowledge and opportunities for the formation of a culture of nutrition and environmental awareness. Unstable eating style is associated with contradictory attitudes and ambivalent food practices.
Genetic features of representatives of Malus Mill. for the formation of identified collections and breeding use
Authors: Ulyanovskaya E V , Chernutskaya E A , Balapanov I M , Stepanov I V , Potapova L S
Published: July 2023

For the active mobilization of bioresources of the leading agricultural fruit plants, especially apple (Malus × domestica Borkh.), and the inclusion of the best samples of the gene pool in the breeding, it is necessary to know their genetic characteristics according to the priority desired traits. The purpose of the study is to study the allelic polymorphism of the Md-PG1 in representatives of Malus Mill. to identify sources of long-term keeping of fruits and to form an identified collection of apple trees for breeding use. The studies were carried out in the Center for Collective Use «Research and Breeding Collection of Genetic Resources of Horticultural Crops»; generally accepted programs and methods of variety study and breeding of apple trees. Based on the data of molecular genetic analysis, carriers of the allelic combination AA for the Md-PG1 gene were identified - apple varieties: Smeralda, Egemen, Georgiya, hybrids 17/1-6-42 (Champion × Modi) and 17/2-5-15 (Renuartsiv × Carmen). The selected varieties and hybrid forms are promising in the process of creating domestic genetic resources with improved quality indicators, including a genetically determined increase in the shelf life of fruits.
The prospects of using Bacillus amyloliquefaciens in the biological control of grape diseases
Authors: Aleinikova Natalia , Galkina Yevgenia , Andreyev Vladimir , Bolotianskaia Elena , Shaporenko Vladimir
Published: July 2023

Currently, the prospects of effective control management in the development of gray (Botrytis cinerea Pers.) and black rot (Macrophoma flaccida (Viala et Rav.) Cav.), as well as the guaranteed preservation of grape yield, can be achieved with the development of ecological approach - the use of microbiological preparations or substances of biological origin. The antagonistic activity of biological fungicide Serenade ASO, SC (titer not less than 1x109 CFU/ml of Bacillus amyloliquefaciens, strain QST 713) was studied in the field research vineyards of the South-Western (SWC) and South Coastal (SCC) viticulture zones of Crimea in 2018-2019. Against the background of weak development of gray rot on bunches of ‘Cabernet-Sauvignon’ grapes (SCC), the maximum biological efficiency was obtained in the variant with five-fold spraying of Serenade ASO, SC, application rate of 5 l/ha and seven days interval. Two-fold protective use of biological preparation Serenade ASO, SC and application rate of 5 l/ha on the plot of ‘Muscat Blanc’ variety (SCC) in 2020 made it possible to control the development of black rot at the level of 76.7-79%. The obtained results indicate good prospects of biological preparation Serenade ASO, SC (titer not less than 1x109 CFU/ml of Bacillus amyloliquefaciens, strain QST 713) to control gray and black rot of grapes during ripening, when the use of chemical fungicides is not appropriate due to their lagged effect.
Improvement of elements of cultivation technology for winter crops and chickpea on chernozems of southern and dark chestnut soils of the Orenburg region
Authors: Yartsev G F , Baikasenov R K , Kolesnikov A A , Akhmetgaliev A T , Episheva Yu Yu
Published: July 2023

The Orenburg region is characterized by a sharp continental climate. It is characterized by cold winters, and frequent droughts in summer. That is why, the most frost-resistant winter wheat and rye of winter crops are cultivated in the region, and the chickpea is the most drought-resistant one of grain legumes. The changing climate requires constant clarification of sowing dates, methods, seeding rates, and emerging new liquid fertilizers require clarification, if possible, of their joint application in certain phases of plant development. In our winter wheat studies, various combinations of liquid fertilizers together with a growth regulator used in the tillering and earing phases were studied, as well as the the sowing dates. Sowing methods and seeding rates have been studied on chickpea. It was revealed that the highest yield of winter wheat is provided by foliar fertilization with liquid nitrogen fertilizer Carb-N-Humik both in the tillering and earing phases. The optimal time for sowing winter crops is the first term, i.e. August 19. The most acceptable method of sowing chickpeas is an ordinary one with a seeding rate of 1.1 million/ha.
Determination of the absolute and relative soil velocity in the bucket of a rotary wire cleaner
Authors: Usmonov T U , Karimov M S , Sh Sharipov Z , Usmanov N K
Published: July 2023

Maintaining the reclamation network in working order requires annual restoration work, which consists in cleaning it from sediment and vegetation, as well as performing various types of repair and construction work. The specificity of the maintenance of irrigation systems is that the specific volumes of excavation are insignificant, and the objects themselves are dispersed over a large area. For the timely and high-quality performance of a large amount of repair and maintenance work on reclamation systems, a significant amount of specialized equipment is required. Recently, a large number of experimental models of sewer cleaning machines and mechanisms for cleaning irrigation systems have been created. At present, when creating new cleaning machines, they are supplied with replaceable working equipment, including for cleaning concreted channels and trays. In the future, the range of interchangeable equipment is planned to be expanded. The article deals with the theory of the movement of the soil particle being cut (deposition) over the working body and the ejection velocity of these particles. When unloading from the tray, which affects the power consumption of the rotor tray-cleaning engine.
Evaluation of the efficiency of sugar beet processing strategies based on the data of the Sergach Sugar Factory
Authors: Balandin Dmitry , Kuzenkov Oleg , Egamov Albert
Published: July 2023

This study is devoted to evaluation of the effectiveness of sugar beet processing strategies, considering the factor of reducing the purity of sugar-containing solutions as a result of long-term storage of raw materials in the conditions of a specific manufacturer - Sergach Sugar Factory. The purpose of the work is to formulate recommendations on the selection of the most effective strategy for manufacturers based on assessments of the effectiveness of various sugar beet processing strategies. As a result of the study, the effectiveness of two heuristic strategies for sugar beet processing was evaluated - “greedy” and “thrifty”. The implementation of both strategies does not require a priori knowledge of all information about changes in the chemical composition of raw materials during storage and is based on current information about the characteristics of the remaining batches of raw materials to the current moment. The “greedy” strategy involves processing the batch of raw materials that currently gives the highest sugar yield, and the “thrifty strategy” - the batch that gives the minimum yield. The efficiency was evaluated by comparing the loss in sugar yield from the implementation of a heuristic strategy compared to the absolute optimum. When calculating the estimated sugar yield, data on the sugar content of various batches of beets and the purity of sugar-containing solutions in the conditions of the Sergach Sugar Factory in 2021 were considered. As a result of the study, it is shown that the “thrifty” strategy has small advantages compared to the “greedy” one. Thus, when choosing a recycling processing in practice, it is better to give preference to the “thrifty” strategy. This makes it possible to increase the total sugar production per season by 100 tons.
Phenotypic Associations With the HMOX1 GT(n) Repeat in European Populations
Authors: Hamilton Fergus , Mitchell Ruth , Ghazal Peter , Timpson Nic
Published: July 2023

Heme oxygenase 1 is a key enzyme in the management of heme in humans. A GT(n) repeat length in the heme oxygenase 1 gene (HMOX1) has been widely associated with a variety of phenotypes, including susceptibility to and outcomes in diabetes, cancer, infections, and neonatal jaundice. However, studies have generally been small and results inconsistent. In this study, we imputed the GT(n) repeat length in participants from 2 UK cohort studies (the UK Biobank study (n = 463,005; recruited in 2006–2010) and the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 937; recruited in 1990–1991)), with the reliability of imputation tested in other cohorts (1000 Genomes Project, Human Genome Diversity Project, and Personal Genome Project UK). Subsequently, we measured the relationship between repeat length and previously identified associations (diabetes, chronic obstructive pulmonary disease, pneumonia, and infection-related mortality in the UK Biobank; neonatal jaundice in ALSPAC) and performed a phenomewide association study in the UK Biobank. Despite high-quality imputation (correlation between true repeat length and imputed repeat length > 0.9 in test cohorts), clinical associations were not identified in either the phenomewide association study or specific association studies. These findings were robust to definitions of repeat length and sensitivity analyses. Despite multiple smaller studies identifying associations across a variety of clinical settings, we could not replicate or identify any relevant phenotypic associations with the HMOX1 GT(n) repeat.
Cuff Size Variation Across Manufacturers of Home Blood Pressure Devices: A Current Patient Dilemma
Authors: Shahi Shamim , Jackson Sandra L , Streeter Taylor E , He Siran , Wall Hilary K
Published: July 2023

BACKGROUND

The American Heart Association (AHA) recommends cuff sizes of blood pressure (BP) monitoring devices based on patient arm circumference, which is critical for accurate BP measurement. This study aimed to assess cuff size variation across validated BP devices and to examine the degree of alignment with the AHA recommendations.

METHODS

Data on home BP devices were obtained from the US BP Validated Device Listing website and listed cuff sizes were compared against AHA recommendations: small adult (22–26 cm), adult (27–34 cm), large (35–44 cm), and extra-large (XL) (45–52 cm).

RESULTS

There were 42 home validated BP devices from 13 manufacturers, and none offered cuffs that were aligned with the AHA recommendations. Over half of the devices (22, 52.4%) were compatible with only a broad-range cuff, generally excluding arm sizes larger than 44 cm. Only 5 devices from 4 manufacturers offered a cuff labeled “XL,” and of these, only 3 devices had sizes that covered the AHA XL range. Terminology lacked consistency with manufacturers using: different labels to describe the same-sized cuffs (e.g., 22–42 cm was labeled “integrated,” “standard,” “adult,” “large,” and “wide range”); the same labels to describe differently sized cuffs (e.g., cuffs labeled “large” were sized 22–42 cm, 32–38 cm, 32–42 cm, 36–45 cm).

CONCLUSIONS

Manufacturers of US home BP devices employ inconsistent terminologies and thresholds for cuff sizes, and sizes were not aligned with AHA recommendations. This lack of standardization could pose challenges for clinicians and patients attempting to select a properly sized cuff to support hypertension diagnosis and management.
Malignancy risk in patients with atopic dermatitis: a population-based cohort study
Authors: Wan Joy , Shin Daniel B , Syed Maha N , Abuabara Katrina , Lemeshow Adina R , Fuxench Zelma C Chiesa , Gelfand Joel M
Published: July 2023

Background

Atopic dermatitis (AD) is associated with immunological dysfunction, which may influence cancer development. Previous studies of AD and cancer demonstrate inconsistent results and few of these studies examined children or AD severity and treatment.

Objectives

To determine malignancy risk among children and adults with AD.

Methods

We conducted a cohort study using electronic health records data from UK general practices in The Health Improvement Network between 1994 and 2015. Children (< 18 years old) and adults (≥ 18 years old) with AD were matched on age, practice and index date to patients without AD. AD was categorized as mild, moderate or severe using treatments and dermatology referrals as proxies. The primary outcome was any incident malignancy, including in situ malignancy, identified using diagnosis codes and categorized into haematological, skin and solid organ malignancies. Secondary outcomes included specific malignancies: leukaemia, lymphoma, melanoma, nonmelanoma skin cancer (NMSC) and common solid-organ cancers.

Results

Among 409 431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) and 1 809 029 children without AD who had median follow-up of 5–7 years, the incidence rates of malignancy were 1.9–3.4 and 2.0 per 10 000 person-years (PY), respectively. The adjusted risk of malignancy overall did not differ with respect to AD [hazard ratio (HR) 1.02 (95% confidence interval 0.92–1.12)]. Severe AD was associated with increased lymphoma risk [HR 3.18 (1.41–7.16), excluding cutaneous T-cell lymphoma (CTCL)], and mild AD was associated with increased NMSC risk [1.55 (1.06–2.27)]. Among 625 083 adults with AD (65.7% mild, 31.4% moderate, 2.9% severe) and 2 678 888 adults without AD who had median follow-up of 5 years, incidence rates of malignancy were 97.4–125.3 per 10 000 PY and 103.7 per 10 000 PY, respectively. The adjusted risk of any malignancy did not differ with respect to AD [HR 1.00 (0.99–1.02)]. However, adults with severe AD had a twofold higher risk of non-CTCL lymphoma. AD was also associated with slightly higher skin cancer risk [HR 1.06 (1.04–1.08)] and slightly lower solid cancer risk [0.97 (0.96–0.98)] but results varied by specific cancers and AD severity.

Conclusions

Epidemiological evidence does not support a strong overall malignancy risk in AD but lymphoma risk may be increased with severe AD.
O17 Endogenous double-stranded RNA (dsRNA) in melanoma: an attack from within
Authors: Sadeq Shaymaa , Plummer Ruth , Chitcharoen Suwalak  , Lovat Penny , Nelson Glyn , Werner Andreas
Published: July 2023

Recent studies have linked endogenous double-stranded RNA (dsRNA) to the development of inflammatory and autoimmune diseases and cancer. However, the scale of dsRNA formation and its biological consequences is still unclear. Malignant melanoma is the most lethal skin cancer, with an increasing prevalence worldwide. Despite the development of immunotherapy and targeted therapies for melanoma, treatment options are still limited for most patients. dsRNA derived from repetitive DNA elements has the potential to stimulate pattern recognition receptors (PRRs). These PRRs can trigger antiviral signalling cascades and induce an interferon response that renders resistant melanoma sensitive to immunotherapy. Consequently, dsRNA can add a new approach to treating melanoma. Tissue culture and molecular biology techniques were used to induce dsRNA formation in melanoma cell lines (with different mitogen-activated protein kinas-activating mutations) using PRRs agonist poly (I:C), azacitidine (Aza) and hydrogen peroxide (H2O2) as stressors. The impact was measured by quantifying cytosolic dsRNA sensors, also known as PRRs (pPKR, MDA5, RIG1 and ADAR1), using reverse transcriptase quantitative polymerase chain reaction and Western blotting. Immunofluorescence and high-resolution microscopy were then applied to investigate dsRNA and its sensors in skin biopsy samples from patients with melanoma. Moreover, the nature of dsRNA in melanoma was studied by isolating native dsRNA from multiple melanoma cell lines by immune enrichment followed by RNA sequencing. Analysis revealed that inducing endogenous dsRNA significantly activates PRR transcripts and protein levels. However, this activation showed different trends. A375 (BRAFV600E) showed robust MDA5 and RIG1 stimulation to poly (I:C) and a mild ADAR1 and PKR response to Aza and H2O2. Meanwhile, C8161 [BRAF wild type (WT)] was resistant to poly (I:C) with a favourable ADAR1 and RIG1 response to Aza. Immunofluorescence analysis of early stages I and II melanoma skin biopsies showed a significant reduction in ADAR1, which melts dsRNA, with increased dsRNA within BRAF-mutant biopsies. RNAseq analysis showed that A375 (BRAFV600E) produced significantly more dsRNA than C8161 (BRAF WT) and primary dermal fibroblasts. The increase was predominantly due to the enhanced production of dsRNA from nuclear DNA. However, about 11% of the reads mapped to the mitochondrial genome vs. 14% and 19% in C8161 and fibroblasts, respectively. In addition, compared to primary dermal fibroblasts, the dsRNA transcriptome of melanoma cell lines shows unique characteristics and altered dsRNA signalling pathways. To summarize, our data support the hypothesis that endogenous dsRNA activates dsRNA sensors and triggers innate immune signalling. Hence, dsRNA signalling may be explored as a potential therapeutic strategy to treat resistant melanoma with an attack from within.
P14 Whole-genome sequencing of malignant cylindroma in CYLD cutaneous syndrome reveals a clinically targetable somatic driver mutation
Authors: Fostier William , Koh Ching Chiek , Husain Akhtar , Namini Shirin , Nik-Zainal Serena , Rajan Neil
Published: July 2023

Metastatic malignant cylindroma (MC) is a rare skin appendageal cancer for which there are no licensed chemotherapeutic interventions and has poor clinical outcomes. MC arising in CYLD cutaneous syndrome (CCS) has been shown to carry pathogenic variants in CYLD and additional driver mutations in TP53. Here we present whole-genome sequencing (WGS) data from MC in a 29-year-old man, revealing a novel clinically targetable somatic driver mutation. The proband presented with a growing, ulcerated cylindroma on the scalp at 28 years of age. He had previously presented with benign cylindromas on the scalp from 8 years of age, attributed to his mother who had CCS. The proband's father and paternal grandmother both had early breast cancer. The proband's sister, aged 33 years, had been recently diagnosed with breast cancer and CCS. Histology of the ulcerated scalp tumour revealed a biphasic neoplasm, showing malignant cylindroma with high-grade features arising within a pre-existing benign cylindroma. Several weeks following excision of the malignant scalp cylindroma, a nodule presented on the left side of the patient's neck; biopsy of the neck lump revealed histology consistent with the metastatic MC. Radiological imaging revealed metastatic deposits of MC in the right axilla, both lungs and the brain. Genetic testing of the proband revealed germline pathogenic variants in both BRCA2 and CYLD, also present in his sister. WGS of the primary MC showed extensive copy number variation, with loss of heterozygosity involving CYLD and BRCA2 loci, not present in a matched control blood sample. Mutational signatures SBS3 and SBS8 were present, consistent with homologous repair (HR) deficiency, and, in addition, SBS13 was detected, suggesting APOBEC-driven mutagenesis. A high HR detect score of 0.999 was reported, consistent with a BRCA-deficient tumour. Additional driver somatic variants in TP53 and PTEN were also detected and are likely to have contributed to tumour pathogenesis. The BRCA deficiency demonstrated in this patient's MC supports the use of poly ADP ribose polymerase (PARP) inhibitors, which have not previously been used to treat MC. This case emphasizes the importance of recognizing coinheritance of tumour suppressor genes in rare genetic conditions, and the utility of rapid WGS to provide novel management options and improve patient outcomes.
P16 How does skin ageing-related basement membrane collagen loss affect the nucleus?
Authors: Summan Simranpreet Kaur , Mayes Andrew , Gunn David , Gautrot Julien , Caley Matthew , O’Toole Edel
Published: July 2023

Skin ageing effects, such as inflammation, oxidative stress, disrupted wound healing and disease, are universal issues. Basement membrane collagens (BMCs) are reduced by ageing and the consequences are poorly understood. BMC sensing of mechanical stress, vital for skin homeostasis, elicits signalling sensed via cytoskeletal actin filaments to the LINC complex (composed of nesprin and sun proteins), nuclear lamina and lamina-associated chromatin. RNAseq data from collagen 7 (Col7) or collagen 17 (Col17) small interfering (si)RNA knockdown primary keratinocytes revealed an opposing enrichment of nuclear function genes. Nesprin-2 was reduced with siCol7 (P < 0.01) vs. siC nontargeting control. We hypothesized that BMC loss in keratinocytes disrupts the nucleocytoskeleton and chromatin organization, dysregulating gene expression and signalling, leading to altered epidermal differentiation and skin barrier impairment. To explore the role of BMC in mechanical stress response, stable short hairpin (sh)RNA knockdowns of Col7 (shCol7) and Col17 (shCol17), and nontargeting control (shC) were generated in immortalized N/TERT cells. Western blot validated knockdowns compared to shC. MTT assays showed a hyperproliferative phenotype with shCol17 compared to shC. Mechanical stretch effect on cells on a flexible membrane was studied by immunofluorescence and Western blot (WB). Images taken from the IN Cell Analyzer confocal microscope were analysed to detect changes in protein expression and localization. Nuclear and cytoplasmic fractions made before and after stretch were analysed by WB. We observed collagen-specific responses to stretch-induced stress with changes to actin and nuclear membrane proteins: emerin and lamin B1, and sun2. Our data are the first to show an altered nucleocytoskeleton in the context of BMC loss and mechanotransduction in skin. This study could provide novel insights into ageing epidermal regulation by BMCs.
P30 Microsatellite instability in cutaneous squamous cell carcinoma
Authors: Holt Georgie , Hayes Christine , Phelps Rachel  , Husain Akhtar , Lamb Christopher , Gallon Richard  , Rajan Neil
Published: July 2023

Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in genes that encode mismatch repair (MMR) proteins. LS is characterized by an increased risk of multiple cancers, including colorectal and endometrial cancer. Muir–Torre syndrome (MTS) is an allelic, phenotypic variant of LS characterized by the presence of skin tumours, including keratoacanthomas and sebaceous tumours. Recently, an association has been proposed between MTS/LS and cutaneous squamous cell carcinoma (cSCC). MTS/LS tumours demonstrate a mutation signature termed microsatellite instability (MSI) that can be used to screen sporadic tumours for underlying MTS/LS. We have previously shown that amplicon-sequencing of microsatellites can detect increased MSI in cSCC in patients with LS. In this study, we assayed a pilot cohort sporadic cSCC in the general population to further explore this potential association. DNA was extracted from cSCC samples. We used an established molecular inversion probe-based protocol to amplify informative microsatellites and sequenced these using the Illumina MiSeq platform. An MSI score was calculated for each tumour sample using a naïve Bayesian approach based on microsatellite deletion frequencies. We found that 5% (n = 1/19) of cSCCs were MSI-high (95% confidence interval 0.1–26.0), which is equivalent to estimated frequencies among unselected sporadic cSCCs in recent literature. We plan to expand our pilot cohort to include a larger series of cSCC and to also carry out somatic sequencing of MSH2, MSH6, MLH1 and PMS2 in tumours to determine if MSI status correlates with MMR gene variant status. Ultimately, this work aims to improve identification of new patients with LS presenting with cSCC and allow them to benefit equitably from preventative cancer surveillance and aspirin chemoprevention.
The risk of venous thromboembolism in atopic dermatitis: a matched cohort analysis in UK primary care
Authors: Warren Richard B , Basey Victoria , Lynam Anita , Curtis Charlotte , Ardern-Jones Michael R
Published: July 2023

Background

Atopic dermatitis (AD) is a common chronic inflammatory skin condition. While other chronic inflammatory conditions are associated with increased risk of venous thromboembolism (VTE), associations between AD and VTE have not been established.

Objectives

We examined whether AD is associated with an increased risk of VTE in a population-based study.

Methods

Electronic health records were extracted from UK general practices contributing to the Optimum Patient Care Research Database (1 January 2010 to 1 January 2020). All adults with AD were identified (n = 150 975) and age- and sex-matched with unaffected controls (n = 603 770). The risk of VTE, consisting of pulmonary embolism (PE) or deep-vein thrombosis (DVT), was compared in people with AD vs. controls using Cox proportional hazard models. PE and DVT were examined separately as secondary outcomes.

Results

We identified 150 975 adults with active AD and matched them with 603 770 unaffected controls. During the study, 2576 of those with active AD and 7563 of the matched controls developed VTE. Individuals with AD had a higher risk of VTE than controls [adjusted hazard ratio (aHR) 1.17, 95% confidence interval (CI) 1.12–1.22]. When assessing VTE components, AD was associated with a higher risk of DVT (aHR 1.30, 95% CI 1.23–1.37) but not PE (aHR 0.94, 95% CI 0.87–1.02). The VTE risk was greater in older people with AD (≥ 65 years: aHR 1.22, 95% CI 1.15–1.29; 45–65 years: aHR 1.15, 95% CI 1.05–1.26; < 45 years: aHR 1.07, 95% CI 0.97–1.19) and those with obesity [body mass index (BMI) ≥ 30: aHR 1.25, 95% CI 1.12–1.39; BMI < 30: aHR 1.08, 95% CI 1.01–1.15). Risk was broadly consistent across mild, moderate or severe AD.

Conclusions

AD is associated with a small increase in risk of VTE and DVT, with no increase in risk of PE. The magnitude of this risk increase is modest in younger people, and those without obesity.
Young stem and leaf anatomy of 15 Malagasy-endemicDiospyrosspecies (Ebenaceae): taxonomic implications
Authors: Sandratriniaina Ninah Andrianasolo , Ramanantsialonina Ravo Nantenaina , Rakouth Bakolimalala , Wiemann Michael C , Hermanson John C , Ravaomanalina Bako Harisoa
Published: July 2023

Eighty-eight of the 255 Diospyros species from Madagascar are potential sources of ebony wood. Unfortunately, several species are currently threatened with extinction due in part to illegal and unsustainable logging. Reliable identification of living Diospyros species is necessary prior to any sustainable exploitation, so as not to compromise those species threatened with extinction. This study aims to identify features that might contribute to supporting taxonomic studies and to provide a complementary tool for the identification of standing trees. Fifteen species of Diospyros endemic to Madagascar were studied using standard anatomical methods. Each species showed a different shape of the leaf midrib and some have distinctive leaf anatomical characteristics, such as the presence of extrafloral nectaries in the distal part of the petiole in Diospyros baronii and filiform sclerenchyma in the mesophyll in Diospyros lewisiae. Statistical analysis showed that petiole and midrib vascular patterns, spongy parenchyma structure, the presence of papillae, thickness of epidermis, presence of extrafloral nectaries, stratification of epidermis, and presence of a cuticle are useful to distinguish species groups and even some species. The anatomy of young stems and leaves of Diospyros species from Madagascar is examined for the first time; the study will be extended to other potentially exploitable species.
The current landscape of therapies for hepatocellular carcinoma
Authors: Coffman-D’Annibale Kelley , Xie Changqing , Hrones Donna M , Ghabra Shadin , Greten Tim F , Monge Cecilia
Published: July 2023

Globally, primary liver cancer is the third leading cause of cancer-related deaths, with approximately 830 000 deaths worldwide in 2020, accounting for 8.3% of total deaths from all cancer types (1). This disease disproportionately affects those in countries with low or medium Human Development Index scores in Eastern Asia, South-Eastern Asia, and Northern and Western Africa (2). Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often develops in the background of chronic liver disease, caused by hepatitis B or C virus, non-alcoholic steatohepatitis (NASH), or other diseases that cause cirrhosis. Prognosis can vary dramatically based on number, size, and location of tumors. Hepatic synthetic dysfunction and performance status (PS) also impact survival. The Barcelona Clinic Liver Cancer (BCLC) staging system best accounts for these variations, providing a reliable prognostic stratification. Therapeutic considerations of this complex disease necessitate a multidisciplinary approach and can range from curative-intent surgical resection, liver transplantation or image-guided ablation to more complex liver-directed therapies like transarterial chemoembolization (TACE) and systemic therapy. Recent advances in the understanding of the tumor biology and microenvironment have brought new advances and approvals for systemic therapeutic agents, often utilizing immunotherapy or VEGF-targeted agents to modulate the immune response. This review will discuss the current landscape in the treatments available for early, intermediate, and advanced stage HCC.